A3.3 Treatment – Data extraction/appraisal Tables · A3.3 Treatment – Data extraction/appraisal...

A3.3 Treatment – Data extraction/appraisal Tables Study ID (ie. Thomas 2009) and citation: Black 2007. Black DW, Arndt S, Coryell WH, Argo T, Forbush KT, Shaw MC, et al. Bupropion in the treatment of pathological gambling: a randomized,

double-blind, placebo-controlled, flexible-dose study. Journal of clinical psychopharmacology. [Randomized Controlled Trial. Research Support, N.I.H., Extramural]. 2007 Apr;27(2):143-50. Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: America

Description of study: randomised controlled trial – level I evidence Patient/population Community sample recruited through advertisements or word of mouth. 28 males and 11 females. Overall Mean age= 43.15, Bupropion mean age=42.8 (19.0) and

placebo mean age=43.5 (19.0). Ethnicity: 32 white and 5 other. N 46 screened. 39 randomised. 17 withdrew Setting Not reported Intervention/indicator N=18, Type=Bupropion, Duration=2 week observation period before randomisation to 12 weeks of double blind treatment, Frequency=Daily, Dose= Initial dose of

75mg/d with increments to 150mg, 225mg, 300mg and 375mg in increments of no more than 150mg/week. Minimum allowable dose was 150mg daily and the mean daily dose of bupropion was 324mg at end point.

Comparison/control N=21, Type=Placebo, Duration=2 week observation period before randomisation to 12 weeks, Frequency=Daily, Dose=Same as intervention. Placebo look alike tablets were used.

Outcomes The primary outcome was the YBOCS-PG. Secondary outcomes included the Gambling Severity Assessment Scale (GSAS), number of gambling episodes (TLFB), time spent on gambling (TLFB), money wagered (TLFB), Clinical Global Impression Improvement and Severity Scales (CGI), Global Assessment of Severity (GAS), ADHD rating scale, HDRS and Sheehan Disability Scale (SDS)

Inclusion Criteria 18 years and over. Spoke standard English. Non-depressed and healthy. Had PG for at least 1 year and had 2 or more gambling episodes in the 2 week screening period. Met the DSM-IV criteria for pathological gambling confirmed through NODS. 5 or more on the South Oaks Gambling Screen (SOGS).

Exclusion Criteria Current (past 3 months) substance misuse and psychiatric co-morbidity, Hamilton Depression Rating Scale (HDRS) score of 18 or more (or a score on item 1 of greater than 2), current eating disorder (except binge eating disorder), history of seizures or suicidal or aggressive behaviour, urine drug screen positive of stimulants, opiates, hallucinogens or phencyclidine, current or past psychotic disorder, bipolar disorder or significant cognitive disorder. Received monoamine oxidase inhibitors within 3 weeks of randomisation, long acting phenothiazines within 3 months of randomisation, fluoxetine within 4 weeks of randomisation or other psychotropic drugs within 2 weeks of randomisation or prior exposure to bupropion. Engagement in individual, group or couples psychotherapy during the 2 weeks before randomisation.

Study Validity

Document evidence of this from the article. Add any other relevant comments, including if this is likely to influence the results of the study

Were there any conflicts of interest in the writing or funding of this study?

No

Grant from National Institutes of Mental Health, Bethesda, Maryland.

Does the study have a clearly focused question?

Yes The current study investigates the efficacy and tolerability of bupropion in the treatment of PG

Is a RCT the appropriate method to answer this question?

Yes

Does the study have specified inclusion/exclusion criteria?

Yes

As above

If there were specified inclusion/ exclusion criteria, were these appropriate?

Yes

Did the study have an adequate method of randomisation?

Yes The pharmacy department developed a randomisation scheme (presumably by random number generation)

Was allocation to intervention group concealed?

Yes The pharmacy department developed a randomisation scheme (presumably by random number generation)

Were patients blind to intervention group?

Yes

Double blind trial

Were investigators and care providers blind to intervention group?

Yes

Double blind trial

Were outcome assessors blind to intervention group?

Yes

All rater administered assessments were made blind to drug or placebo assignment.

Aside from the experimental intervention, were the groups treated the same?

Yes

Was there sufficient duration of follow-up?

No

After study completion, subjects were followed up at months 1,3 and 6.

All outcomes were measured in a standard, valid and reliable way?

Partial

The YBOCS has excellent psychometric properties. G-SAS has shown good reliability and validity. The psychometric properties for the other instruments were not been mentioned.

Were outcomes assessed objectively and independently?

Yes

Standardised tools were used and all rater administered assessments were blinded.

Was the study sufficiently powered to detect any differences between the groups?

No

The study was relatively small and a larger sample could have provided greater statistical power to show differences between the groups and to reduce the possibility of a type II error. Although sufficient power was projected this was based on the assumption that we would be able to recruit more subjects and that the drug/placebo difference would be 0.30 or more.

If statistical analysis was undertaken, was this appropriate?

Partial

- Linear mixed effects model was performed - means and standard deviations provided for baseline only - no exact means and SDs for endpoint or follow up data therefore have to infer from graph provided - data was checked for normality - missing data was handled appropriately: "except for the CGI-I score, in which subjects had to have at least 1 postbaseline measure, all subjects were included in the analysis, including the 8 who dropped out before a postbaseline assessment - no mention of covariates or subgroups

Were the groups similar at baseline with regards to key prognostic variables?

Partial

The placebo group scored higher on the YBOCS-PG urge/thought subscale and the SDS work subscale. The placebo group also wagered more on average than the bupropion group. Although statistically significant these baseline differences do not affect the tests of bupropion efficacy because each test compares changes from baseline.

What percentage of the individuals recruited into each arm of the study dropped out?

Treatment=56% Control=33%

8 patients dropped out before post-baseline assessment. A total of 17 patients withdrew from the study with no significant group difference.

Were all the subjects analysed in the groups to which they were randomly allocated (ie intention to treat analysis)?

Yes

Subjects assigned to the drug or placebo group were included in the intent to treat analysis.

Is the paper free of selective outcome reporting?

Partial

The number of gambling episodes was not reported.

Were the outcomes measured appropriate?

Yes

Need to contact the author(s) to clarify?

Yes

Other

What is the overall risk of bias?

Low

Level of evidence Level II

Results The study results indicate that although subjects treated with either bupropion or placebo experience significant improvement as early as the first week of treatment, bupropion was not statistically superior to placebo at any time point. Author’s conclusions

The study results indicate that although subjects treated with either bupropion or placebo experience significant improvement as early as the first week of treatment, bupropion was statistically superior to placebo at any time point. The fact that subjects in both groups experienced statistically significant improvement suggests that PG and perhaps other impulse control disorders have high placebo response rates. The results contribute to the mixed picture that has emerged from other randomised clinical trials of PG, all complicated by high placebo response rates, high rates of subject non-completion or both. Hollander et al have observed that the initial high placebo response rate declines over time, allowing placebo differences to emerge and argue that PG may require lengthy therapeutic trials. Alternatively, future studies may benefit from an extended lead-in period. Additional trials are called for to see whether other medications may be beneficial in treating PG. Further work also needs to explore behavioural treatments of PG particularly ones based on CB principles that already have shown promise in treating the disorder perhaps in combination with MI. Studies should also focus on a detailed assessment of clinical characteristics that could be associated with treatment response.

Study ID (ie. Thomas 2009) and citation: Blanco 2002. Blanco C, Petkova E, Ibanez A, Saiz-Ruiz J. A pilot placebo-controlled study of fluvoxamine for pathological gambling. Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists. [Clinical Trial. Comparative Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2002 Mar;14(1):9-15.

Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: Spain

Description of study: randomised controlled trial – level I evidence Patient/population Outpatient (recruited from the Pathological Gambling Outpatient Program). 32 participants: 21 males and 11 females. Overall mean age=42.1. Fluvoxamine: mean

age=42.3(12.7) and placebo: mean age=41.9(11.1) N 32 participants were assessed for inclusion and randomised and 15 participants withdrew. Setting Pathological Gambling Outpatient Program of the Department of Psychiatry of Hospital Ramon y Cajal in Madrid, Spain Intervention/indicator N=15, Type: fluvoxamine, Duration: 6 months, Frequency: daily, Dose: single dose of 100mg/day during first 2 weeks then 200mg/day for the rest of the trial. Comparison/control N=17, Type: placebo, Duration 6 months, Frequency: daily Outcomes The primary outcome measure was the change in the average amount of money spent on gambling per week in the last month or the last 2 weeks for the 2 week

assessment. Number of hours per week spent gambling was a secondary outcome measure. Inclusion Criteria Meeting the DSM-III-R criteria for pathological gambling Exclusion Criteria Meeting the criteria for another axis I diagnosis, including any substance abuse (except nicotine dependence) or any unstable medical condition.

Study Validity



Yes

Grant from Duphar, SA, Barcelona, Spain


Yes

We report the results of the first double-blind, parallel, placebo controlled study for the treatment of pathological gambling over a period of 6 months, and explore the presence of potential predictors of treatment response.


Yes


Yes


Yes


Not reported


Not reported


Yes

Double blind trial


Yes

Double blind trial


Not reported


Yes


No

Patients were assessed at baseline, 2 weeks, 4 weeks and then monthly until the end of the study (6 months) no follow up after 6 months (end of trial)


No Used self report data


No


No

The power of the study was limited by the high placebo response rate (59%). we had estimated that with a placebo response of 30% and a drug response of 6O%, we would have a power of 90% to detect a statistically significant difference in the number of responders. In contrast, a post hoc analysis showed that, with our sample size and given the placebo response rate of 59% in the intent to treat sample in the current study, a response rate of 99% in the fluvoxamine group would have been needed to have a power of 80% to detect a statistically significant difference between the two groups.


No

Used correct techniques for the type of data, however, based on the small sample size the statistical analysis was inappropriate.


Yes

Patients in the placebo and fluvoxamine groups were similar at baseline in all demographic and severity measures


treatment=80%, control=41%

More people dropped out from fluvoxamine than placebo group but difference in attrition was not statistically significant. Reasons for dropout were side effects, lack of compliance, symptomatic improvement


Yes

Intention to treat


Yes

All the planned outcomes were measured and reported


Yes


Yes

Other

What is the overall risk of bias? High High - Few or no criteria fulfilled or the conclusions of the study are likely or very likely to be affected.

Level of evidence Level II or III-1

Results There were no significant differences in the proportion of responders between patients treated with fluvoxamine and those assigned to placebo for the overall trial. However, in the more powerful LMEM models the rate of decline of dollars spent on gambling approached significance (p<0.09) in the unadjusted model and became significant when gender and age were entered in the model. Author’s conclusions There are currently no established treatments for pathological gambling. A few reports have suggested that a variety of treatment modalities may benefit some patients, but more definitive controlled clinical trials are needed to confirm and quantify the efficacy of those strategies. Our study, partially supporting the findings of Hollander et al., suggests that fluvoxamine may be efficacious in the treatment of at least a subgroup of pathological gamblers. However, more studies with larger samples are needed before the efficacy of fluvoxamine can be confirmed.

Study ID (ie. Thomas 2009) and citation: Carlbring 2008. Carlbring P, Smit F. Randomized Trial of Internet-Delivered Self-Help With Telephone Support for Pathological Gamblers. Journal of Consulting and Clinical Psychology. 2008;76(6):1090-4.

Initials of person extracting/appraising data: SM Type of publication: Brief report Language of publication: English Country study was conducted: Sweden

Description of study: randomised controlled trial – level I evidence Patient/population Community sample recruited through media announcements. Of 66 participants 94% were male and the mean age was 31.9 years SD=9.8. The main culprits were

video lottery terminals (36.4%), Internet poker (21.2%), sports betting (12.1%) and horses (10.6%). Only gamblers with mild to moderate levels of depression were included.

N 224 assessed for inclusion. 66 fulfilled the criteria and were randomised. Setting Internet delivered self help Intervention/indicator N=34. 8 week Internet based CBT program with minimal therapist contact via email and weekly telephone calls of less than 15 minutes. First four modules had a

motivational interviewing focus and included building motivation for change. The following four modules were based on CBT. Once weekly a telephone call was made by therapists to each participant. The purpose was to provide positive feedback and encouragement as well as to answer any questions of the participant about the modules. The therapists were two social workers with an additional two years of basic training in CBT and MI. Both therapists had good MI skills according to the MI Treatment Integrity Code. The mean total time per week spent on each participant in this study was approximately 30 min and included telephone calls, administration, and response to e-mails.

Comparison/control N=32. Wait list control. Outcomes NODS, Hospital Anxiety and Depression Scale (HADS-A and HADS-D), and QOLI. Clinical Global Impression of Improvement at 18 and 36 month follow up only. Inclusion Criteria Meet the DSM-IV-TR criteria for pathological gambling according to the 1 month version of the NODS, have a total score of <21 on the MADRS depression scale

and < 4 on the suicide item, 18 years and over, live in Sweden and have gambled at least once in the last 30 days Exclusion Criteria People were excluded for not living in Sweden, too young, playing computer games without betting money, fewer than 5 criteria, not currently gambling and

severely depressed

Study Validity



No

Study funded by a grant from the Swedish National Institute of Public Health


Yes

This trial compared Internet-administered self-help that included minimal therapist contact via e-mail with a wait-list condition. To maximize compliance, we supplemented the treatment with short weekly telephone calls.


Yes


Yes


Yes


Yes

Participants were randomly allocated to the conditions by an online, true random number service independent of investigators and therapists


Yes

Participants were randomly allocated to the conditions by an online, true random number service independent of investigators and therapists


No

Not possible to blind participants


No

Not possible to blind investigators and care providers


Yes

At 18 and 36 months, an independent clinician, blind to treatment status, conducted clinical global impression interviews over the telephone.


Yes


Yes

Self report measurements were taken at baseline and 3 months in both conditions and at 6, 18 and 36 month follow up for intervention group only. However, as people on the waiting list, for ethical reasons, received treatment before the follow-up data were collected, there was unfortunately no between-group comparison at follow-up.


Yes

The NODS has been reported to show promise as an outcome measure of gambling. The outcome measures have good psychometric properties even when administered via the internet (referring to HADS and QOLI)


Yes

The measures used are a standardised tool and the outcome assessors were blinded for the most part


Not reported


Yes

Two different approaches were employed for the main analysis. The first used t tests with imputation according to the last observation-carried-forward method in case of missing data. The second approach employed a random effects model, which is not sensitive to missing data. Finally, in the treatment group, the follow-up measurements were compared with the baseline scores, with the t test for paired observations used in order to evaluate effect maintenance. - Performed statistical tests and gave descriptive and inferential statistics - The mean and standard deviations were provided - No mention of normality - No mention of confounding variables or subgroup analysis - No mention of adjustment for multiple testing


Yes

Table 1 shows that randomisation resulted in a balanced distribution across both conditions; all ts(65)< 1.08, all ps> .28.


Post-treatment: treatment= 6%, control=12.5%


Yes

Intention to treat. Imputation according to the last observation carried forward method in case of missing data.


Yes

All planned outcomes were measured and reported on.


Yes


Yes

Other

What is the overall risk of bias? Low Low - All of the criteria have been fulfilled or where criteria have not been fulfilled it is very unlikely the conclusions of the study would be affected.


Results The treated participants achieved significant improvement on measures of pathological gambling, general anxiety, depression, and quality of life. Moreover, the treatment effects were maintained up to 36 months, at which time three quarters of the randomised participants showed a moderate or large improvement as judged by an independent clinician. Author’s conclusions As we did not include a comparison treatment, specificity of the findings cannot be assured. Consequently, future studies should investigate the issue of specificity of Internet-based self-help interventions, the role of community online support, and the nonspecifics of therapist contact that are likely to be present in both telephone and Internet consultations. Additionally, comparisons with standardized face-to-face therapy are imperative. Dismantling studies are strongly encouraged in order to evaluate the costs and benefits of briefer or more intensive combined treatments.

Study ID (ie. Thomas 2009) and citation: Cunningham 2009. Cunningham JA, Hodgins DC, Toneatto T, Rai A, Cordingley J. Pilot Study of a Personalized Feedback Intervention for Problem Gamblers. Behavior Therapy. 2009;40(3):219-24.

Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country study was conducted: Canada

Description of study: randomised controlled trial – level I evidence Patient/population Community sample recruited from an ongoing typology study where participants were recruited via newspaper advertisements. Personalised feedback group

mean age= 41.2 (9.2) and control group mean age= 47.5 (11.8). 37.5% males in P.F group and 58.3% males in control group. N 61 were recruited at baseline and 49 returned their 3 month follow up survey Setting Personalised feedback was mailed to the participants. Intervention/indicator n=24, Treatment: personalised feedback intervention. Respondents in the intervention condition were mailed their personalised feedback summary. The

personalized feedback materials start out with a brief statement of the purpose of the report. The person is then provided with a summary of the number of different types of gambling they engage in along with a comparison of how this total number compares to other Canadians of their sex. A list is then provided of all of the gambling activities that the person engaged in at least once a month. For each of the gambling activities listed, the person is then provided with a graph that visually demonstrates where their gambling fits in comparison with other Canadians. The feedback then provides a summary of their CPGI score, along with a description of what it means. The feedback continues with a list of the actual problems the respondent reported on the CPGI. The next section comprises a description of the types of gambling cognitions that the person endorsed on the GCQ, a measure of the cognitive distortions the person holds about gambling. The feedback is brief and should take 10-20 minutes to read.

Comparison/control n= 25, Treatment: wait list control. Respondents in the control condition were sent a list of possible components of a self-help intervention and asked to consider whether such information would be useful for gamblers. Respondents in the control condition were sent a personalized feedback summary after returning their 3-month follow-up materials.

Outcomes CPGI and Gambling Cognitions Questionnaire were assessed at baseline. At 3 month follow up: The CPGI and (1) In the past 3 months, how much money, not including winnings, did you spend on all of your gambling activities? (2) In the past 3 months, what is the largest amount of money you have gambled with on any given day?

Inclusion Criteria Meet criteria for gambling dependence using DSM-IV Exclusion Criteria

Study Validity



No

This project was funded by the Ontario Problem Gambling Research Centre


Yes

A pilot study was then undertaken of this intervention in order to obtain preliminary information on the efficacy of the materials. The hypothesis for this pilot evaluation was that problem gamblers who received the personalized feedback intervention would reduce their gambling more than problem gamblers who did not receive any intervention by a 3-month follow-up.


Yes


Partial

No specified exclusion criteria


Yes

The specified inclusion criteria was appropriate


Yes

A random numbers list was used. No stratification was employed.


No


No


No

Blinding was not possible


No


Yes


No

3 month follow up


Partial

The CPGI has adequate reliability, however, the outcomes of total amount spent and maximum spent were self report data with no verification.


Partial

Whilst one of the outcomes was assessed using a standardised tool, two of the outcomes were subjective self report data and the outcome assessors were not blinded.


Not reported Statistically significant results were found


Yes

- The test was appropriate for a continuous outcome. - Hierarchical regression was suitable, allowed to control for baseline differences. - Addressed the issue of normality and where required performed a square root transformation - Point estimates and measures of variability were provided - Potential confounders were identified and taken into account


Partial

Age and education level were significantly different between conditions


19.7% overall dropout from baseline to 3 month follow up


No


Yes


Yes


Yes

Other



Results There was a significant impact (p<.05) of intervention condition on the total amount of money spent. Although the impact of the intervention was in the same direction for the maximum amount of money spent on one occasion and for CPGI scores at follow-up, these analyses did not reach significance. Inspection of the means indicated that respondents who received the personalized feedback summary reported spending less money on gambling at the 3-month follow-up than those in the control condition. Author’s conclusions At 3-month follow-up (80.3% follow-up rate, N= 49), after controlling for baseline demographic characteristics and gambling severity, respondents in the feedback condition displayed some evidence that they were spending less money on gambling than those in the control condition. Further, ratings of the usefulness of the feedback summary were positive and most recipients (96%) recommended that they be made available to other gamblers interested in evaluating or modifying their gambling. Given these promising pilot results, a full-scale evaluation of these personalized feedback materials would appear justified.

Study ID (ie. Thomas 2009) and citation: Dannon 2005A. Dannon PN, Lowengrub K, Gonopolski Y, Musin E, Kotler M. Topiramate versus fluvoxamine in the treatment of pathological gambling: a randomized, blind-rater comparison study. Clinical neuropharmacology. [Clinical Trial. Comparative Study. Randomized Controlled Trial]. 2005 Jan-Feb;28(1):6-10.

Dannon PN, Lowengrub K, Musin E, Gonopolsky Y, Kotler M. 12-Month follow-up study of drug treatment in pathological gamblers: A primary outcome study. Journal of Clinical Psychopharmacology. 2007;27(6):620-4.

Initials of person extracting/appraising data: SM Type of publication: peer reviewed journal article Language of publication: English Country study was conducted: Israel

Description of study: randomised controlled trial – level I evidence Patient/population Topiramate group mean age=34.9 (17.2) and fluvoxamine group mean age= 36.8 (16.9). All males. Majority Moroccan Jew followed by Eastern European Jew and

Israeli born. N N=31. Setting Completed at Rehovot Community Mental Health and Rehabilitation Clinic Intervention/indicator N=15. 12 week duration. Topiramate was started at 25mg/d and increased to 50mg/d on day 3. Then increased by 50mg every 3 days until reaching dose of

200mg/d on day 12. Comparison/control N=16. 12 week duration. Fluvoxamine was started at 25mg/d and increased to 50mg/d on day 3 and then increased by 50mg every 3 days until reaching a dose of

200mg/d at day 12. Outcomes Hamilton Rating Scale for Anxiety, Hamilton Depression Rating Scale, CGI-Improvement Scale, YBOCS and SOGS. Inclusion Criteria DSM-IV diagnosis of pathological gambling, South Oaks Gambling Screen of 5 or more and age between 18 and 65 Exclusion Criteria Comorbid diagnosis on Axes I and II, clinically unstable medical problems and previous treatment with either fluvoxamine or topiramate.

Study Validity



No

Although the manufacturers of topiramate and fluvoxamine supplied the study medication for this study the authors have no financial or other relationship with the manufacturers or with any other drug company.


Yes

We therefore conducted a randomised 12 week study to compare the effectiveness of topiramate versus fluvoxamine in the treatment of PG.


Yes


Yes

As above


Yes


Not reported Randomised fashion


Not reported


No

Only raters were blinded. The patients and treating physicians were not blind to treatment


No



Yes



Yes


No

No follow up.


Yes

Psychometric properties were not reported, however, they have been shown to be psychometrically sound tools.


Yes

Standardised tools were used and the outcome assessor was blinded.


Not reported


No

- Independent samples t-tests and repeated measures ANOVA were performed which were appropriate for the type of data - Poor reporting of significance tests and associated statistics means that the results cannot be properly interpreted. Unclear whether the descriptive statistics are percentages or means and standard deviations


Yes

Shown in table


Topiramate=3/15=20%, Fluvoxamine=8/16=50%

2 topiramate patients dropped out due to side effects and one without notice to receive treatment in private practice. 5/8 fluvoxamine dropped out because of side effects, 2 for noncompliance and one because of legal problems.


Not reported


No

Everything except for the SOGS was reported on


Yes


Yes

Other



Results 12 of the 15 patients from the topiramate group completed the 12 week treatment. 9 of the 12 topiramate completers reported full remission of gambling behaviour and 3 completers had a partial remission. The CGI-I score was significantly better for the topiramate group at the 12 week visit compared with baseline (F=10.5, P<0.01, df=2,31). In the fluvoxamine treatment group 8/16 patients completed the study and 6/8 fluvoxamine completers reported full remission and the remaining 2/8 reported a partial remission. The fluvoxamine group showed improvement in the CGI-I score at week 12 although this difference was not significant (F=3.7, P,0.08, df=2,31). Author’s conclusions Topiramate may represent a useful option in the pharmacological treatment of PG. A larger, placebo controlled study is needed to confirm our preliminary findings.

Study ID (ie. Thomas 2009) and citation: Dannon 2005B. Dannon PN, Lowengrub K, Musin E, Gonopolski Y, Kotler M. Sustained-release bupropion versus naltrexone in the treatment of pathological gambling: a preliminary blind-rater study. Journal of clinical psychopharmacology. [Comparative Study. Randomized Controlled Trial]. 2005 Dec;25(6):593-6.

Dannon PN, Lowengrub K, Musin E, Gonopolsky Y, Kotler M. 12-Month follow-up study of drug treatment in pathological gamblers: A primary outcome study. Journal of Clinical Psychopharmacology. 2007;27(6):620-4.

Initials of person extracting/appraising data: SM Type of publication: brief report Language of publication: English Country the study was conducted: Israel

Description of study: randomised controlled trial – level I evidence Patient/population Outpatient. All males. Mean age=29.1 (17.3). Majority Moroccan Jews, followed by Eastern European Jews and Israeli borns. N N=36 Setting The study was started and completed at Rehovot Community Mental Health and Rehabilitation Clinic Intervention/indicator N=17. 12 week duration. Type: Sustained release Bupropion. Dose: Started at 150mg/d for the first week and then increased to 300mg/d in 2 divided doses. After

3 weeks 14 of 17 bupropion SR partial and non responders were increased to a total daily dose of 450mg/d and the 3 remaining patients remained on 300mg/d. Comparison/control N=19. 12 week duration. Type: Naltrexone. Dose: Started at 25mg/d for first 4 days and then increased to 100mg/d in 2 divided doses. After 3 weeks 6 of 19

partial or non responders were increased to a daily dose of 150mg/d and the remaining 13 stayed on 100mg/d Outcomes Hamilton Rating Scale for Anxiety, Hamilton Depression Rating Scale, CGI-Severity Scale, and SOGS at baseline. The CGI-Improvement scale administered at weeks

2,4,8 and 12. The patients self reports of number and time spent gambling were assessed at each follow up visit although structured interview not performed. Inclusion Criteria DSM-IV criteria of pathological gambling, South Oaks Gambling Screen score of 5 or more and age between 18 and 65. Exclusion Criteria Co-morbid diagnosis on Axes I and II, unstable medical problems, abnormal liver function tests and a history of seizure disorder

Study Validity



Not reported


Yes

The purpose of this study was to examine the comparable efficacy of bupropion SR versus naltrexone in the treatment of PG.


Yes


Yes


Yes


Not reported Patients were assigned in a randomised manner.


Not reported


No


No


Yes

Blind rater study


Yes


No

No follow up


Partial

Used HRSA, HRSD, CGI and YBOCS to measure outcomes. No mention of psychometric properties, however, they have been shown to be validated and reliable tools. Also used self reports to assess number and time spent gambling without a structured interview


Partial Whilst the outcome assessor was blinded subjective self report data was used


Not reported


No

- It is unclear what group comparisons are being evaluated with particular statictical tests and these are not possible to interpret with any degree of confidence. - Did not address normality - The effects of drop outs were not evaluated


Yes

Shown in table


5/17=29.41% for bupropion and 6/19=31.58% for naltrexone

Among the 5 bupropion non-completers 4 dropped out due to side effects such as dizziness, vertigo and gastrointestinal disturbances and the other patient left the outpatient clinic without notice to receive treatment in private practice. All 6 of the naltrexone non-completers dropped out during the first month of treatment due to side effects such as vomiting, nausea, dizziness, agitation, insomnia and other orthostatic hypotension


Not reported


Partial

YBOCS was not mentioned in methods section, however, was included in the results table.


Yes


Yes

Other



Results The majority of patients responded well to the drug treatment. 12/17 patients in the sustained release bupropion group completed the 12 week study and 13/19 naltrexone patients completed the study. 9/12 (75%) completers were rated as full responders in the sustained release bupropion group versus 10/12 (76%) in the naltrexone group. 3/12 (25%) completers in the bupropion group were rated as partial responders. In the naltrexone group, 3/13 (23%) of completers were rated as partial responders. Author’s conclusions The preliminary study shows that sustained release bupropion may be effective as naltrexone in the treatment of PG. Further studies are needed to confirm our findings.

Study ID (ie. Thomas 2009) and citation: Diskin 2009. Diskin KM, Hodgins DC. A randomized controlled trial of a single session motivational intervention for concerned gamblers. Behaviour Research and Therapy. 2009;47(5):382-8.

Initials of person extracting/appraising data: SM Type of publication: peer reviewed journal article Language of publication: English Country the study was conducted: Canada

Description of study: randomised controlled trial – level I evidence Patient/population Community sample recruited through advertisements, posters and tv appearances. Mean age= 45 (10.6) years and 43% (35/81) were women. 60.5% reported

concerns with video lottery terminals. 33.3% reported concerns with slot machines. Gambling on card and dice games was a concern for 18.5% and 6.2% reported concerns with bingo. 6.2% reported problems with lottery type games and sports select lotteries.

N 136 called to express interest in study and 97 randomised.83 attended interviews and 81 included in the analyses. Setting University of Calgary Intervention/indicator N=42. Motivational Intervention. In the MI interview therapists employed the counselling skills that Miller and Rollnick (1991, 2002) incorporated in the MI

approach, including reflective listening, summarizing, and supporting self-efficacy. The protocol included a number of specific techniques such as a discussion of the good and not so good things about gambling, a decisional balance exercise and a readiness ruler for motivation to change gambling. The intervention was manualised in order to ensure that all participants were offered a similar experience; however, the therapists were free to follow the discussion as it occurred rather than force participants to follow the format exactly. In order to control for therapist effects, two doctoral students each delivered half of the CI and half of the MI.

Comparison/control N=39.Control Intervention. The CI interview included the SCID II modules for histrionic, narcissistic, obsessive compulsive and avoidant personality disorders. These semi-structured modules were intended to provide a consistent structure for the control interviews. The modules were not presented as a form of assessment; rather they were used as a basis for conversation with the participants, in which the therapists used the modules to structure a credible interview. Participants were encouraged to talk about their gambling during the course of the interview, with the semi-structured format allowing the therapists to maintain consistency among interviews. The interviewers were asked to be interested and pleasant and to avoid using any specific MI techniques or offering any specific recommendations for behaviour change. Specifically, the interviewers would respond naturally to the participants (for example – ‘‘It sounds like you have had a lot of trouble with this’’ or ‘‘this has been really hard for you’’), but would not use a form of summary that would be used in an MI (for example – ‘‘It sounds like there are a lot of things you enjoy about gambling, but it has also been causing some problems with.’’). When emotions were aroused during the interview the interviewers were empathic and supportive.

Outcomes Timeline follow back interview for number of days and dollars gambled, NODS, SOGS, PGSI-CPGI and Global Severity Index of the Brief Symptom Inventory. Inclusion Criteria Over age 17, scoring 3 or more on the Problem Gambling Severity Index of the Canadian Problem Gambling Index, had gambled in the 2 months preceding the

interview, willing to provide the name of a collateral informant and willing to provide follow up data on gambling Exclusion Criteria Currently receiving treatment for problem gambling and unable to speak English well enough to participate.

Study Validity



No

Funding provided by Alberta Gaming Research Institute


Yes

Exploring the effectiveness of a face-to-face motivational interview and provision of a self-help workbook on gambling behaviour among individuals who were experiencing concerns about their gambling but who were not seeking treatment. The study included a control interview condition in order to explore the effect of a motivational interviewing approach over and above generic therapist contact.


Yes


Yes


Yes


Yes

Computer generated urn-randomisation process


Not reported


Not reported


Not reported


Yes

Telephone interviews were performed by a research assistant who was blind to group assignment


Yes


Yes

Follow up occurred at 1,3,6 and 12 months


Yes

Psychometric properties were addressed and the outcomes were measured in a valid and reliable way. Collaterals were also used to verify data.


Yes

Standardised tools were used and the outcome assessor was blinded


Not reported Statistically significant differences were found


Partial

- Pearson's t-tests and Chi-square tests were used to examine baseline differences. Linear mixed models were used to test the reduction in gambling behaviour. One way ANCOVA was used to measure psychological distress and gambling severity. - Potential confounders were identified and taken into consideration - Missing data was handled appropriately - Provide mean and standard error but no standard deviation for the primary outcome - Normality was not addressed


Yes

Analyses did not reveal any significant between groups differences on any of the variables.


X% treatment

X% control/ comparison

With the inclusion of missing data supplied at a later interview, follow-up rates were as follows: 79/81 (97.5%) at 1 month, 76/81 (93.8 %) at 3 months, 74/81 (91.4 %) at 6 months and 69/81 (85.2%) at 12 months. At the 12-month interview nine members of the CI group and three members of the MI group were lost to follow-up. The participants lost from the study were higher in baseline gambling levels and distress


Yes

An intention to treat approach where the baseline values or the 4 week interview values were carried forward. The analysis was also conducted using the sample of participants who completed at least the 3 month interview.


Partial

Did not report on the NODS scores


Yes


Yes

Other

What is the overall risk of bias? Low

Low - All of the criteria have been fulfilled or where criteria have not been fulfilled it is very unlikely the conclusions of the study would be affected.


Results The results of this study indicate that for individuals who were concerned about their gambling, a brief motivational intervention was helpful in reducing gambling behaviours. For 12 months after receiving an MI, participants spent less money gambling per month and fewer days gambling per month than those assigned to the CI condition. The MI appears to have had an effect over and above the effect of participating in the study, being assessed at baseline and at follow-up, interacting with a therapist and receiving a self-help manual. It appears that people in the MI group experienced reduced levels of psychological distress over the course of the study. Whereas participants in the CI group did not report any significant changes in their overall level of distress (as measured by the Global Severity Index of the Brief Symptom Inventory) at the 12-month interview, the mean global level of distress for the MI group was significantly reduced (to within one standard deviation of the population mean). Overall, participants in both the CI and MI groups reported reductions in problem gambling symptoms, based on their reduced scores on the SOGS and CPGI over the course of the study. Author’s conclusions

This study adds to the growing support for the use of motivational interventions in changing problem gambling behaviour. What is special about MI? Perhaps most importantly, it is the willingness to acknowledge and accept the gambler’s ambivalence about the possibility of changing their behaviour. Rather than demanding a firm commitment for change, coupled with a complete rejection of ‘‘the good things’’ that gambling is perceived to provide, the interviews encouraged participants to talk about both the positive and negative aspects of their gambling behaviour. The motivational intervention in this study was intended to support the participants as experts on themselves, the only people with the self-knowledge to evaluate the possibility of change and the expertise to understand what actions they would have to take if they chose to make changes. The interviews provided an opportunity for participants to explore their values, to think about the future and to think about the people and principles they held dear. These discussions were often emotionally charged interactions in which the interviewer played a supportive and non-judgemental role, allowing participants to express and acknowledge their feelings about their behaviour and to imagine the possibility of change. The MI approach does not impose any expectations for change on the client, and is likely, therefore to be more acceptable than an approach that ‘‘expects’’ change as a given.

Study ID (ie. Thomas 2009) and citation: Dowling 2007. Dowling N, Smith D, Thomas T. A comparison of individual and group cognitive-behavioural treatment for female pathological gambling. Behaviour research and therapy. [Comparative Study. Randomized Controlled Trial]. 2007 Sep;45(9):2192-202. Dowling N, Smith D, Thomas T. Treatment of female pathological gambling: the efficacy of a cognitive-behavioural approach. Journal of Gambling Studies. 2006;22(4):355-72.

Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: Australia

Description of study: randomised controlled trial – level I evidence Patient/population Community sample recruited through advertisements and radio announcements. Mean age=43.47. All females N 81 assessed and 56 randomly allocated Setting Outpatient Intervention/indicator (a) n=14, individual 12 session CBT program, Individual treatment sessions were 1.5h in length, M=22.2 (13.2) weeks treatment period. (b) n=17, 12 weekly Group

treatment sessions were 2h in length and group size ranged from 4-6. All participants in group treatment completed the sessions in 12 weeks. Treatment goal of either abstinence or controlled gambling but only those who chose abstinence were reported.

Comparison/control (c) n= 25. Wait list control group. None of the participants were receiving psychosocial or supportive therapy for PG. Outcomes Gambling behaviour measures: frequency, duration, amount of money inserted and expenditure.

Psychological functioning measures: BDI, STAI and Coopersmith Self-esteem Inventory. DSM-IV-TR criteria. Inclusion Criteria A preferred gambling modality of gaming machines and a gambling problem that satisfied the diagnosis of pathological gambling. Exclusion Criteria

Study Validity



Not reported


Yes

The current study therefore aimed to determine the differential efficacy of a cognitive-behavioural treatment program for female pathological gamblers delivered in an individual and group format. Specifically, it was hypothesised that treatment conducted using an individual format would produce superior outcomes than treatment conducted using a group format.


Yes


Partial No specified exclusion criteria


Yes


Yes Computer generated randomisation schedule


Yes Preparation of envelopes containing treatment allocation by person not involved in trial.


No Not possible


No Not possible


No


Yes


No

6 month follow up


Yes

Psychometric properties of instruments used were addressed and adequate.


Partial

Standardised tools were used, however, the outcome assessors were not blinded.


Not reported Statistically significant differences were found


Yes

- The statistical analysis performed was appropriate for the type of data - The primary analyses were initially conducted on a treatment completer (non-intention-to-treat) basis. These analyses were then repeated using a conservative intention-to-treat approach - The means and standard deviations were reported - No mention of normality


Yes

No differences in demographic variables and no significant multivariate differences between groups in gambling behaviour and psychological functioning.


The treatment attrition rate, expressed as the proportion of pathological gamblers commencing treatment who did not complete treatment, did not differ for individual (14%) or group (0%) treatment


Yes

The primary analyses were initially conducted on a treatment completer (non-intention-to-treat) basis. These analyses were then repeated using a conservative intention-to-treat approach, whereby baseline values were carried forward as treatment/waiting list values for participants who failed to complete the treatment program/waiting list, and treatment/post-treatment or available follow-up values were carried forward as follow-up values for participants who were not available for the complete duration of the follow-up period.


Yes


Yes


Yes

Other


Moderate

Moderate - Some of the criteria have been fulfilled and those criteria that have not been fulfilled may affect the conclusions of the study.


Results The findings indicate that while gambling behaviour and most psychological functioning outcomes did not differ as a function of the format of treatment, group treatment failed to produce superior outcomes to the control group in relation to several measures of psychological functioning (i.e., state anxiety and self-esteem). Moreover, by the completion of the six-month follow-up period, 92% of gamblers treated with the individual format no longer satisfied diagnostic criteria compared with 60% of those treated with the group format. These findings are consistent with the very limited treatment outcome literature that has provided some indication that group treatment may be somewhat less effective than individual treatment Author’s conclusions In conclusion, this is the first known treatment outcome study of pathological gambling to evaluate the differential efficacy of the same treatment program delivered in individual and group formats. This study found that while individual and group treatments generally produced comparable outcomes in terms of gambling behaviour and psychological functioning, there was a tendency for individual treatment to produce superior outcomes. Given that several other treatment outcome studies have also provided some indication that group treatment may be somewhat less effective than individual treatment, some caution should be employed when delivering cognitive-behavioural treatment programs in a group format until further research is conducted to investigate the efficacy of such treatment.

Study ID (ie. Thomas 2009) and citation: Fong 2008. Fong T, Kalechstein A, Bernhard B, Rosenthal R, Rugle L. A double-blind, placebo-controlled trial of olanzapine for the treatment of video poker pathological gamblers. Pharmacology, biochemistry, and behavior. [Controlled Clinical Trial. Journal Article]. 2008 May;89(3):298-303.

Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: America

Description of study: randomised controlled trial – level I evidence Patient/population Community sample (treatment seeking pathological gamblers who were recruited through newspaper advertisements). Treatment group mean age=46.6 (12.5)

years and control group mean age= 43.6 (9.0). Only video poker players. 11 males and 10 females N 23 randomised, 2 dropped out. N=21. Setting Conducted at the Trimeridian Gambling Center Intervention/indicator N=9. Treatment: olanzapine. Duration: 7 weeks. Dose: 2.5 mg for the first week, 5.0 mg for the second week, 7.5 mg for the third week and 10.0 for weeks four to

seven Comparison/control N=12. Treatment: placebo. Duration: 7 weeks. All subjects were encouraged to attend GA. Outcomes The primary outcome measures for PG for this trial included craving and gambling behaviour measures. For craving, the Brecksville Gambling Craving Scale (BGCS)

and the Desire to Gamble Scale (DGS) were used. Outcome measures for gambling behaviour included the Clinical Global Impression for Pathological Gambling (CGI-PG) and a Gambling Behaviour Diary which reported frequency, money spent and time spent on gambling. Secondary outcome measures to evaluate effects on general psychiatric health included the Brief Psychiatric Rating Scale (BPRS), the Beck Depression Inventory, the Hamilton Depression and Anxiety Rating Scales (HAM-A, HAM-D) and the Barratt Impulsiveness Scale (BIS).

Inclusion Criteria Between the ages of 18 and 65, video poker primary game of choice and normal laboratory assessment and vital signs Exclusion Criteria The need for immediate hospitalisation, the presence of suicidal ideation, diagnosis of a major Axis I disorder, current prescription of psychotropic medications

and diagnosis of a medical disorder in which the administration of olanzapine was contraindicated.

Study Validity



Yes

Study was funded by an investigator-initiated project by Eli Lilly and Company (global pharmaceutical company)


Yes

The current study was conducted to obtain data regarding the safety, tolerability, and potential efficacy of olanzapine for the treatment of pathological gambling.


Yes


Yes


Yes


Not reported


Not reported


Yes

Double blind study


Yes

Double blind study


Not reported


Yes


No

No follow up


Partial

In the discussion, the authors reported outcome measures may not have been sensitive or specific enough to detect the effects of olanzapine. This study utilized outcome instruments that have been used by clinicians that treat pathological gamblers along with tracking gambling behaviours. Outcome measures used in other pharmacological trials of pathological gamblers, such as the Pathological Gambling Yale-Brown Obsessive Compulsive Scale (PG-YBOCS), or the Gambling Symptom Assessment Scale (G-SAS) were not selected for use in this study because the study was completed before their use increased in clinical trials. This suggests that rather than basing their choice of outcome measure on the psychometric properties of the instruments, the decision was determined by the amount of times the instruments had been reported to be used in other studies which does not seem appropriate.


Partial

Only some of the tools were standardised and we are not aware of whether the outcome assessor was blinded


No

Power analysis was not conducted because the purpose of the study was a preliminary one designed to detect any differences based on a small sample.


Yes

- measures of gambling behaviour were log transformed to achieve normal distribution - means and standard deviations were reported - analysis was appropriate for the type of data - dropouts were excluded from the analyses, however, the dropout rate was very small for this kind of study


Yes

Table on demographic and key variables. Not significant.


2/23=9% Two of the participants dropped out of the study following the onset of side effects, of sedation and fatigue, both of which are expected with olanzapine.


No

No intention to treat. 2 participants did not complete the entire protocol, they were excluded from the analysis


No

Do not provide the baseline data for the DGS or the post-treatment data for the BDI. It is also unclear which of the gambling craving scales were reported on.


Yes


Yes

Other



Results These results revealed that the pathological gamblers enrolled in this study consistently reported reduced gambling urges, reduced gambling behaviour, and improved mood state; however, treatment with olanzapine was not associated with significantly improved outcomes over placebo. Although pathological gamblers demonstrated reduced gambling behaviours after treatment, their overall improvement, in both groups, as measured by the clinician's global impression (CGI) was minimal and not statistically significant. Olanzapine was well-tolerated and there were no adverse events. The treatment retention was high and there were no notable extrapyramidal effects. Author’s conclusions Although this preliminary study does not provide support of efficacy for olanzapine in video poker pathological gamblers, future studies that examine its role with pathological gamblers with co-occurring bipolar disorder or other co-occurring impulse control disorders is warranted. An additional avenue to explore is the role of medication in impacting gambling urges and cravings. Furthermore, subtyping pathological gamblers through a predictor analysis (based on level of impulsivity or receptor genetics) might be a way of differentiating out the subsets of pathological gamblers that are likely to respond to this medication.

Study ID (ie. Thomas 2009) and citation: Grant 2003. Grant JE, Kim SW, Potenza MN, Blanco C, Ibanez A, Stevens L, et al. Paroxetine treatment of pathological gambling: a multi-centre randomized controlled trial. International clinical psychopharmacology. [Clinical Trial. Multicenter Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2003 Jul;18(4):243-9.


Description of study: randomised controlled trial – level I evidence Patient/population Males and females outpatients recruited from newspaper advertisements and by referals for medical treatment. 30 women and 46 men with mean age=45.4 N 94 screened and 76 randomised Setting Outpatient clinics Intervention/indicator Patients entered 1 week placebo run in phase and patients reporting a 30% or greater reduction in the score of PG-YBOCS between initial and randomisation visits

were deemed placebo responders and were not randomised. n=36. Treatment: paroxetine. Duration: 16 weeks. Frequency: daily. Dose: 10mg/d during week 1, 20mg/d during week 2 with flexible dosing up to 60mg/d, based on clinical response and tolerability.

Comparison/control n=40. Treatment: placebo. Duration: 16 weeks. Frequency: daily. Dose: parallel to treatment Outcomes Screening and baseline assessments: SOGS, PG-YBOCS, CGI-Severity scale, G-SAS.

Efficacy and safety assessments: The primary outcome measure was the PG-CGI-I. Secondary outcome measures were the PG-YBOCS, G-SAS, G-SAS subscale, investigator rated PG-CGI-S. Other assessments performed at baseline and at the end of study treatment were the Sheehan Disability Inventory, HAM-D and HAM-A.

Inclusion Criteria 18 years and over. Meet DSM-IV criteria for pathological gambling. Score of 5 or more on the SOGS. Women's participation contingent on negative results of a beta-human chorionic gonadotropin pregnancy test and stable use of a medically accepted form of contraception.

Exclusion Criteria Current Axis I diagnosis determined by SCID except for nicotine dependence or simple phobia. Past history of bipolar disorder, schizophrenia or other psychotic disorder. Alcohol or substance dependence or abuse in the past 3 months. Baseline scores greater than 18 on either HAM-D or HAM-A. Concomitant psychotropic medication. Participation in individual or group psychotherapy or Gamblers Anonymous. Unstable coexisting medical condition.

Study Validity



Yes

Financial support provided by the GlaxoSmithKline Pharmaceuticals


Yes

To examine further the tolerability and efficacy of paroxetine in the treatment of pathological gambling, we conducted a multicentre, placebo-controlled study.


Yes


Yes


Yes


Unclear Patients were randomised 1:1


Yes Randomisation was performed by a technician, with no clinical contact, who kept the coding during the trial.


Yes

Double blind


Yes

Double blind


Not reported


Yes


No

No follow up


Yes

Instruments used have previously been shown to have adequate psychometric properties even though not stated in this study


Partial

Even though standardised tools were used, we are not aware whether the investigators were blinded


No

The moderate sample size may have precluded the identification of treatment outcomes between groups. Such trends in a small sample may suggest that a larger study might well register a significant difference.


Partial

- A wide range of tests were used which appeared to have been conducted appropriately - Baseline differences found but not controlled for in the analyses - Means and standard deviations were reported - The dropout rate was high and was not adequately explained, however, the analyses was performed on both an intention to treat and observed case dataset.


Partial

Significant between group difference on PG-YBOCS urge/thought scale and gender


Paroxetine: 15/36=41.67%

Placebo: 16/40=40%

21 of 36 paroxetine patients and 24 of 40 placebo patients completed all study visits


Yes

Intention to treat included all patients who were randmoised to double blind study medication with at least one post baseline efficacy assessment. Statistical analyses used both a last observation carried forward and the observed case dataset.


No

They do not report on the HAM-A and HAM-D results.


Yes


No

Other


High

High - Few or no criteria fulfilled or the conclusions of the study are likely or very likely to be affected.

Level of evidence II or III-1

Results Both the paroxetine- and the placebo-treated groups demonstrated comparable improvement at 16 weeks (59% response rate in the paroxetine group, 49% rate in the placebo group; chi squared=0.737; d.f.=1; P=0.390). Paroxetine consistently resulted in a greater percentage of responders at each study visit compared to placebo but failed to demonstrate statistical superiority to placebo on scores on the Clinical Global Impressions scale, the Yale-Brown Obsessive-Compulsive Scale Modified for Pathological Gambling, or the Gambling Symptom Assessment Scale. High rates of symptom improvement were observed in pathological gamblers receiving either paroxetine or placebo after 16 weeks.

Author’s conclusions There are currently no Food and Drug Authority approved treatments for pathological gambling. Although paroxetine treatment was associated with an earlier response, paroxetine and placebo treated groups demonstrated comparable overall improvement. Further studies are needed to determine the extent to which these gains are maintained over time within each group, and the mechanism underlying the improvements.

Study ID (ie. Thomas 2009) and citation: Grant 2006A. Grant JE, Potenza MN, Hollander E, Cunningham-Williams R, Nurminen T, Smits G, et al. Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. The American journal of psychiatry. [Comparative Study. Multicenter Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2006 Feb;163(2):303-12.


Description of study: randomised controlled trial – level I evidence Patient/population Recruited through newspaper advertisements and referrals for medical treatment. Mean age=45.9 (11.4). 90 women. N 308 screened and 207 randomised Setting Outpatient psychiatric treatment centres Intervention/indicator (A) n=52, Treatment: nalmefene, Frequency: daily, Dose: 25mg/d, Duration: 16 weeks. (B) n=52, Treatment: nalmefene, Frequency: daily, Dose: 50mg/d, Duration:

16 weeks. (C) n=52, Treatment: nalmefene, Frequency: daily, Dose: 100mg/d, Duration: 16 weeks. Treatment was initiated at 25mg/d of nalmefene. At week 2 the subjects randomly assigned to receive the 50mg/d or 100mg/d began receiving higher doses. After week 2 the subjects continued to take the doses to which they were randomly assigned.

Comparison/control (D) n=51, Treatment: placebo, Frequency: daily. Duration: 16 weeks. Outcomes Primary outcome: PG-YBOCS. Each subscale was used as a secondary efficacy measure. Secondary outcomes: G-SAS, CGI-Improvement scale and SDS. Inclusion Criteria 18 years and older, primary DSM-IV diagnosis of pathological gambling (SCID), 5 or more on the SOGS, at least moderate urges to gamble within week before

entering the study (score of 2 or more on the urge component of the G-SAS), gambling behaviour within 2 weeks before enrollment and female participants required to have a negative beta-human chorionic gonadotropin pregnancy test result and a medically accepted form of contraception.

Exclusion Criteria Current axis I disorder determined with the SCID, except for nicotine dependence, lifetime history of bipolar I disorder or bipolar II disorder, dementia, schizophrenia or any psychotic disorder determined with the SCID, current or recent (past 3 months) DSM-IV substance abuse or dependence, treatment for pathological gambling (other than Gamblers Anonymous) within the last 6 months, baseline score of >17 on either the 17-item Hamilton Depression Rating Scale (HAM-D) or the Hamilton Anxiety Rating Scale (HAM-A), infrequent gambling (e.g., lottery and bingo) that did not meet the DSM-IV criteria for pathological gambling, positive results on a urine drug screen (except for cannabis), unstable medical condition and concomitant use of psychotropic medication.

Study Validity



Yes

Supported by BioTie Therapies Corp. Dr. Kallio and Mr. Nurminen are employees of BioTie Therapies Corp. No other author has any significant commercial relationships to disclose relative to the study or the article.


Yes

On the basis of encouraging preliminary reports of the efficacy of naltrexone in pathological gambling and nalmefene’s lack of hepatotoxicity, we conducted a large double-blind, randomised, multicenter trial of nalmefene for pathological gambling. We hypothesized that nalmefene would reduce gambling symptoms (urges/thoughts and behaviours) in subjects with pathological gambling.


Yes


Yes


Yes


Yes Subjects were randomly assigned in blocks of eight by using computer-generated randomisation (with no clinical information)


Not reported


Yes

Double blind


Yes

Double blind


Not reported


Yes


No

No follow up


Yes

Instruments used were said to be valid and reliable


Partial

Standardised tools were used however we are unaware of whether the outcome assessors were blinded


Yes

To detect a mean difference of 4.4 with 80% power and a 5% significance level in a two-sided test, 43 subjects per group were needed. To account for expected dropouts, we chose 50 as the number of subjects needed per group.


Partial

- the tests performed were appropriate for the type of data (linear mixed effects model) - normal distribution was assumed for the PG-YBOCS and normality for the other outcomes were addressed - means and standard deviations were provided at baseline only - missing data was handled with intention to treat - the dropout rate was fairly high, however, the reasons for dropout were addressed and weren’t significantly different between the groups - not entirely clear what number the analysis was based on


Yes

No statistically significant differences between groups (Table 1).


placebo: 27/51=52.9%, 25mg/d: 33/52=63.5%, 50mg/d: 37/52=71.2%, 100mg/d: 37/52=71.2%

The following categories of reasons for premature discontinuation were defined in the study protocol: adverse events, lack of efficacy, loss to follow-up, subject withdrawal, or other. Premature discontinuation was common in all groups, with 66% of all randomly assigned subjects dropping out before week 16. Twenty-four (47%) of 51 subjects assigned to the placebo group and 49 (31%) of 156 subjects assigned to a nalmefene group completed the 16- week trial. The most common reasons for discontinuation in subjects taking nalmefene were adverse events (47%, N=50 of 107) and loss to follow-up (31%, N=33 of 107). Significantly more and earlier discontinuations in the groups receiving 50 mg/day and 100 mg/day of nalmefene, compared to the placebo group. Discontinuation in the group receiving 25 mg/day of nalmefene did not differ significantly from that in the placebo group.


Yes

All subjects who were randomly assigned to study groups were included in the intent-to-treat analyses. In all efficacy analyses, only subjects with at least two post-randomisation observations were included (to guarantee that a slope for a linear regression line could be calculated), except for the analysis of CGI improvement, where only one evaluation was required.


Yes


Yes


No

Other


Moderate



Results In this multicenter, randomised, double-blind clinical trial, we found that nalmefene was superior to placebo in the treatment of pathological gambling across a spectrum of illness-specific and global outcome measures. The results demonstrate that nalmefene treatment reduces the symptoms associated with pathological gambling. Of the three fixed doses evaluated, the 25 mg/day and 50 mg/day doses demonstrated superior efficacy, compared to placebo, on the primary efficacy measure (Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling total score) and secondary efficacy variables, including the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling behaviour and urge/ thought subscale scores and the Gambling Symptom Assessment Scale total score. Only the 25 mg/day dose demonstrated efficacy superior to placebo in terms of the overall response to treatment (measured by the CGI). The 100 mg/day dose seemed to confer no additional benefit, compared to the lower dose levels, on any efficacy measure, and the upper limit of the dose range we selected thus seems to have been unnecessarily high. Author’s conclusions Subjects who received nalmefene had a statistically significant reduction in severity of pathological gambling. Low-dose nalmefene (25 mg/day) appeared efficacious and was associated with few adverse events. Higher doses (50 mg/day and 100 mg/day) resulted in intolerable side effects. This investigation suggests that nalmefene may be effective in the acute treatment of pathological gambling. Although optimal dosing and titration of nalmefene cannot be determined from this study, lower doses and a slower titration should be considered for future studies. As effective treatments for pathological gambling emerge, it becomes increasingly important that physicians and mental health care providers screen for pathological gambling in order to provide timely treatment.

Study ID (ie. Thomas 2009) and citation: Grant 2006B. Grant JE, Potenza MN. Escitalopram treatment of pathological gambling with co-occurring anxiety: an open-label pilot study with

double-blind discontinuation. International clinical psychopharmacology. [Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2006 Jul;21(4):203-9. Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: America

Description of study: randomised controlled trial – level I evidence Patient/population Community sample recruited via newspaper advertisements for medication treatment N N=13 of open label phase. Mean age=55.8.

N= 4 of double blind discontinuation phase. Setting Not reported Intervention/indicator n=3. This study consisted of a 1 week placebo lead in where those not found to be placebo responders were started on unblinded escitalopram 10mg/day for 2

weeks. The dose was then increased to 20mg/day at visit 4 and 30mg/day at visit 6 unless clinical improvement was achieved at a lower dose. Duration: 1 week placebo lead in, 11 weeks of open-label escitalopram and then 8 weeks of double blind discontinuation phase. Those PG subjects who were considered responders (30% or greater reduction in PG-YBOCS) were offered inclusion in the double blind discontinuation phase. This phase consisted of subjects being randomised either to the escitalopram dose at which they completed the open label phase or placebo.

Comparison/control n=1. Placebo, 8 week discontinuation phase. Those randomised to placebo were first tapered over 2 weeks if response was achieved at 30mg/day or 1 week if response was achieved at 20mg/day

Outcomes Primary outcome measure was: PG-YBOCS. Secondary measures: HAM-A, HAM-D, G-SAS, CGI, SDS, Perceived Stress Scale, Quality of Life Inventory. Inclusion Criteria DSM-IV criteria for PG assessed by SCI-PG, clinically significant anxiety determined by score of 14 or more on HAM-A, score of 5 or more on SOGS, gambling

behaviour within 2 weeks prior to enrolment and women's participation required negative results on a beta-human chorionic gonadotropin pregnancy test and stable use of a medically accepted form of contraception.

Exclusion Criteria Infrequent gambling (less than once a week) that did not meet DSM-IV criteria for PG. Unstable medical illness or clinically significant abnormalities on lab tests, electrocardiogram or physical examination at screen, history of seizures, myocardial infarction within 6 months, current pregnancy, lactation or inadequate contraception in women of childbearing potential, a need for medication other than escitalopram with possible psychotropic effects or unfavourable interactions with escitalopram, clinically significant suicidality, current Axis I disorder determined by SCID and SCID compatible modules for impulse control disorders except for any anxiety disorder or nicotine dependence, a lifetime history of bipolar disorder type I or II, dementia, schizophrenia or any psychotic disorder determined by SCID, current (past 3 months) DSM-IV substance abuse or dependence, positive urine drug screen at screening, initiation of psychotherapy or behaviour therapy within 3 months prior to study baseline, previous treatment with escitalopram or citalopram and treatment with investigational Medication or depot neuroleptics within 3 months, with fluoxetine within 6 weeks or with other psychotropics within 2 weeks prior to study baseline.

Study Validity



Yes

This study was supported by an unrestricted educational grant from Forest Pharmaceuticals to Drs Grant and Potenza.


Yes

The current pilot study examined the tolerability and efficacy of escitalopram in the treatment of PG with co-occurring anxiety.


Yes


Yes


Yes


Not reported Simply states randomly assigned


Not reported


Yes

Double blind study


Yes

Double blind study


Not reported


Yes


No

No follow up


Yes

All tools were valid and reliable.


Partial

Standardised tools were used. Not aware if outcome assessor was blinded.


Not reported

Only 4 subjects continued on to the discontinuation phase. No statistical tests were done.


N/A

The sample size was too small and didn’t allow for statistical analyses.


Not reported

Not reported for the 4 participants that stayed on for the double blind discontinuation phase


The one subject in the placebo group discontinued treatment due to worsening symptoms


Yes

Intention to treat with last observation carried forward. Completer analysis also performed.


Partial

For the open label phase of the study all the outcomes are reported on, however, for the double blind discontinuation phase only the data on the PG-YBOCS and HAM-A scores were given.


Yes


Yes

Other



Results Gambling symptoms after the open label phase, during the 8 week discontinuation phase, showed a mild worsening that did not reach clinical or statistical significance. In the case of the subject assigned to placebo, gambling symptoms returned within 4 weeks and the subject discontinued treatment due to worsening symptoms. Author’s conclusions Although PG is not a labelled condition of escitalopram or any serotonin reuptake inhibitor, the present study suggests that escitalopram may be effective in the acute treatment of PG with co-occurring anxiety. As safe and effective treatments for PG emerge, it becomes increasingly important that generalist physicians and mental health care providers screen for PG to provide timely treatment.

Study ID (ie. Thomas 2009) and citation: Grant 2007. Grant JE, Kim SW, Odlaug BL. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biological psychiatry. [Comparative Study. Randomized Controlled Trial. Research Support, N.I.H., Extramural]. 2007 Sep;62(6):652-7.


Description of study: randomised controlled trial – level I evidence Patient/population Recruited by newspaper advertisements. Only give demographic data on all 27 participants not the 13 who continued on the discontinuation phase separately N 27 completed 8 week open label phase and 13 agreed to continue with double blind continuation Setting Not reported Intervention/indicator n= 6. Treatment: N-Acetyl Cystein. The study consisted of 8 weeks of open-label NAC. All eligible study subjects were started on unblinded NAC 600 mg/day for 2

weeks. The dose was then increased to 1200 mg/day for 2 weeks and increased again to 1800 mg/day for the remainder of the study. Those subjects who “responded” to open-label NAC (response being defined a priori as a 30% or greater reduction in PG-YBOCS total score at end point compared with baseline) were included in to the double blind discontinuation phase and randomised to either the NAC dose at which they completed the open label phase or to an equivalent number of identical appearing placebo capsules containing lactose powder. No adjustments were made to dosage during the double blind phase. The double-blind phase lasted 6 weeks, with subjects seen every 2 weeks.

Comparison/control n=7. Treatment: placebo. The study consisted of 8 weeks of open-label NAC. All eligible study subjects were started on unblinded NAC 600 mg/day for 2 weeks. The dose was then increased to 1200 mg/day for 2 weeks and increased again to 1800 mg/day for the remainder of the study. Those subjects who “responded” to open-label NAC (response being defined a priori as a 30% or greater reduction in PG-YBOCS total score at end point compared with baseline) were included in to the double blind discontinuation phase and randomised to either the NAC dose at which they completed the open label phase or to an equivalent number of identical appearing placebo capsules containing lactose powder. No adjustments were made to dosage during the double blind phase. The double-blind phase lasted 6 weeks, with subjects seen every 2 weeks.

Outcomes The primary outcome was PG-YBOCS. Secondary measures: G-SAS, CGI- Improvement and Severity scale, SDS, HAM-D, HAM-A. Secondary measure used only at baseline and open label study end point was QOLI

Inclusion Criteria All subjects met the DSM-IV criteria for PG with the clinician-administered Structured Clinical Interview for Pathological Gambling (SCI-PG). All subjects were required to have gambled within 1 week before enrollment. Eligible subjects were required to have a score of 15 or greater on the PG-YBOCS. Women’s participation required negative results on a beta-human chorionic gonadotropin pregnancy test and stable use of a medically accepted form of contraception.

Exclusion Criteria Exclusion criteria included: (1) infrequent gambling (i.e., < one time/week) that did not meet DSM-IV criteria for PG; (2) unstable medical illness or clinically significant abnormalities on physical examination at screen; (3) history of seizures; (4) myocardial infarction within 6 months; (5) current pregnancy or lactation or inadequate contraception in women of childbearing potential; (6) lifetime history of bipolar disorder type I or II, dementia, schizophrenia, or any psychotic disorder determined by Structured Clinical Interview for DSM-IV (SCID); (7) current or recent (past 3 months) DSM-IV substance abuse or dependence; (8) positive urine drug screen at screening; (9) initiation of psychotherapy or behaviour therapy within 3 months before study baseline; and (10) previous treatment with NAC. Subjects who were currently taking psychotropic medications were allowed into the study as long as the dose of medication had been stable for 3 months before study inclusion and there were no plans to modify the dose during the study duration. Similarly, subjects attending Gamblers Anonymous were allowed to participate if attendance had been ongoing for at least 6 months before study entry. Subjects who changed doses of medication or started therapy or Gamblers Anonymous, on the basis of their self-report, were discontinued from the study.

Study Validity



Yes

This research was supported in part by a Career Development Award (K23 MH069754-01A1) to JEG. Dr. Grant has been a consultant to Somaxon Pharmaceuticals and has received research grants from Somaxon Pharmaceuticals, Forest Pharmaceuticals, and GlaxoSmithKline.


Yes

We conducted a pilot study to examine the tolerability and efficacy of NAC in the treatment of PG. We hypothesized that on the basis of NAC’s potential to reduce drug cravings, it would reduce gambling cravings as well as the gambling behaviour that results from cravings in individuals with PG.


Yes


Yes


Yes


Yes Randomised by the university’s investigational pharmacy (in blocks of four with computer-generated randomisation with no clinical information)


Yes Randomised by the university’s investigational pharmacy (in blocks of four with computer-generated randomisation with no clinical information)


Yes

Double blind


Yes

Double blind


Not reported


Yes


No

No follow up


Yes

All measures were reported to be valid and reliable


Partial

Standardised tools were used. Not aware if outcome assessors were blinded


No

The double-blind findings in this study showed only a trend toward significance. It is possible, however, that a larger study, appropriately powered, might demonstrate a significant separation from placebo.


Partial

- The tests used were appropriate for the type of data and easy to interpret (Mann-Whitney test) - Normality was addressed - Did not mention missing data - No mention of confounding variables


Not reported


Not reported


Not reported

States that they used an intention to treat analysis but it is unclear if this was for both phases of study or just the open label phase.


Partial

All the outcomes for the 8 week open label phase were reported, however, only the PG-YBOCS, G-SAS and SDS were reported on for the 6 week double blind discontinuation phase


Yes


Yes

Other


Moderate



Results Of those assigned to NAC, 83.3% still met responder criteria at the end of the double-blind phase, compared with only 28.6% of those assigned to placebo (Fisher exact test = .078; φ coefficient -.55 considered “relatively strong” [Rea and Parker 1992]; Figure 1). There was also a statistical trend for NAC to maintain improvement on the primary outcome measure (PG-YBOCS total score) and two secondary outcome measures (PG-YBOCS urge subscale and G-SAS) Author’s conclusions This investigation suggests that NAC might be effective in the acute treatment of PG. As effective treatments for PG emerge, it becomes increasingly important that physicians and mental health care providers screen for PG in order to provide timely treatment. Given the open-label design of the study and the small number of subjects participating (particularly in the discontinuation component), the interpretation of the efficacy results of this study is limited.

Study ID (ie. Thomas 2009) and citation: Grant 2008. Grant JE, Kim SW, Hartman BK. A double-blind, placebo-controlled study of the opiate antagonist naltrexone in the treatment of pathological gambling urges. The Journal of clinical psychiatry. [Randomized Controlled Trial. Research Support, N.I.H., Extramural]. 2008 May;69(5):783-9.


Description of study: randomised controlled trial – level I evidence Patient/population Community sample recruited through newspaper advertisements for medication treatment. 30 males and 47 females. Placebo mean age=44.7 (9.67) and

naltrexone mean age=47.8 (9.65). 51.9% identified nonstrategic (e.g. Slot machines, lottery) forms of gambling as their primary type of gaming N N=77. Setting Univeristy of Minnesota Intervention/indicator Eligible subjects received placebo for 1 week and those who were not found to be placebo responders were randomly assigned to one of the four conditions.

n=58. There were 3 treatment groups: naltrexone 50mg/day, 100mg/day or 150mg/day. Duration: 17 weeks. Frequency: daily. Dose: Treatment was initiated at 25mg/day for all subjects for 2 days and then the dose was increased to 50mg/day. All subjects were given 4mg/day of ondansetron for the first 3 days to reduce nausea. At week 3 subjects randomly assigned to 50 mg/day continued at that dose while subjects assigned to the naltrexone 100mg/day or 150mg/day were raised to the higher doses. There were no significant differences among the 3 naltrexone groups on baseline characteristics, study outcomes, treatment completion, medication compliance or adverse drug experiences therefore data from naltrexone groups were combined.

Comparison/control n=19. Treatment= placebo. Duration: 17 weeks. Frequency: daily. Dose: same as above. Outcomes The primary outcome measure was PG-YBOCS and secondary measures were G-SAS, CGI- Severity scale, SDS, HAM-A and HAM-D Inclusion Criteria Met DSM-IV-TR criteria for PG assessed by SCI-PG, at least moderate urges to gamble as determined by a score of 2 or more on item 1 of the G-SAS, 5 or more on

the SOGS, gambling behaviour within 2 weeks prior to enrolment and women's participation required negative results on a beta-human chorionic gonadotropin pregnancy test and stable use of a medically accepted form of contraception.

Exclusion Criteria Infrequent gambling that didn't meet the DSM-IV-TR criteria for PG. Unstable medical illness, clinically significant abnormalities on lab tests or physical examination at screening visit. Current pregnancy, lactation or inadequate contraception. Need for medication with possible psychotropic effects or with unfavourable interactions with naltrexone. Lifetime history of bipolar disorder type I or II, dementia, schizophrenia or any psychotic disorder determines by SCID. Current DSM-IV-TR substance abuse or dependence. Positive urine drug screening (excluding cannabis). Initiation of psychotherapy or behavioural therapy within 3 months prior to study baseline. Previous treatment with naltrexone. Baseline scores of 26 or higher on HAM-D or HAM-A. Clinically significant suicidality. Treatment with investigational medication or depot neuroleptics within 3 month, with fluoxetine within 4 weeks or other psychotropics within 2 weeks prior to study baseline.

Study Validity



Partial

This research was supported in part by a Career Development Award and a grant from the National Institute of Mental Health. Dr Grant has served as a consultant to Pfizer and has received grant/research support from GlaxoSmithKline and Forest.


Yes

This study sought to replicate and extend the findings from the previous trial. Unlike the previous study we enrolled PG subjects with a range of co-occurring disorders and extend treatment trial to 18 weeks


Yes


Yes


Yes


Yes Participants were randomly assigned in blocks of 8 using computer generated randomisation with no clinical information


Not reported


Yes

Double blind study


Yes

Double blind study


Not reported


Yes


No

No follow up


Yes

Instruments used were said to be valid and reliable


Partial

Standardised tools were used. Not aware if outcome assessors were blinded.


Yes

A retrospective power analysis was performed using a bootstrap approach. The results indicate that the significant findings reported are not likely to be based on chance.


Partial

- The tests used were appropriate (chi-square and ANOVA), however, the results reported were incosistent (df). - Confounding variables were addressed and taken into account - Did not mention normality - Means and standard deviations were reported - Missing data was handled appropriately as the analyses was conducted on an intention to treat and completers sample


Yes

There were no statistically significant imbalances regarding age, sex, marital status, education or gambling severity between treatment groups.


placebo: 6/19= 31.58% and naltrexone: 22/58=37.93%

Placebo: 13/19 and naltrexone: 36/58 completed the study. Of the 28 who failed to complete the study 20 either withdrew consent for personal reasons or were unable to comply with study schedule, 5 withdrew due to adverse events and 3 felt the study was not helping their gambling. The rate of completion did not differ between treatment groups.


Yes

Analyses were performed on all available data as well as for completers. All available post-randomisation data were first analysed and a secondary supportive analysis of completers was performed.


Yes


Yes


Yes

Other


Moderate



Results Analysis of the 3 active arms failed to demonstrate any significant increase in effects associated with increased dose. Hence, the active arms were combined and compared to placebo. Significantly better results were observed for those assigned to naltrexone on the primary efficacy variable, the PG-YBOCS total scores. A significant treatment effect which continued throughout the study was first detected after 6 weeks on active medication. The difference among group was statistically significant on the urge and behaviour subscale of the PG-YBOCS. G-SAS analysis demonstrated statistically significant differences between groups in patient reported gambling symptoms. Author’s conclusions This investigation suggests that naltrexone may be effective in the acute treatment of PG when subjects report urges to gamble. As effective treatments for PG emerge, it becomes increasingly important that physicians and mental health care providers screen for PG in order to provide timely treatment

Study ID (ie. Thomas 2009) and citation: Grant 2009. Grant JE, Donahue CB, Odlaug BL, Kim SW, Miller MJ, Petry NM, et al. Imaginal desensitisation plus motivational interviewing for pathological gambling: randomised controlled trial. Br J Psychiatry. [Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't]. 2009 Sep;195(3):266-7.

Initials of person extracting/appraising data: SM Type of publication: Brief report Language of publication: English Country the study was conducted: America

Description of study: randomised controlled trial – level I evidence Patient/population 43 females and 25 males with a mean age of 48.7 (12.8) years N N=68 Setting Not reported Intervention/indicator n=33. Treatment: CBT consisted of 6 sessions each lasting 1 hour over an 8 week period (the MI component was included in session 1). Individuals in the CBT

group began therapy 1 week after baseline assessment, were seen weekly for 6 sessions. One week after the final session they returned for evaluation. Comparison/control n=35. Treatment: referral to GA (wait list control). Participants in the GA group received a list of meeting times and locations for 75 GA meetings throughout the

Twin Cities metropolitan area. Individuals assigned to GA returned after 8 weeks for follow up. People in this group were given 6 sessions of CBT beginning 1 week following the 8 week post GA assessment.

Outcomes The primary outcome measure was PG-YBOCS. Secondary measures were G-SAS, CGI-severity scale, HRSD, HAS, SDS and QOLI Inclusion Criteria Men and women aged 18 to 75 with pathological gambling and who had gambled at least once per week for the past 2 months were included. Exclusion Criteria Past 3 month substance use disorder; positive urine drug screen at screening; current psychotherapy or medication for pathological gambling; previous GA

attendance; suicidal ideations and current use of psychotropic medications.

Study Validity



Partial

Supported by an NIMH career development award. J.E.G. has received research grants from Forest Pharmaceuticals, GlaxoSmithKline and Somaxon Pharmaceuticals, he has been a consultant to Somaxon Pharmaceuticals and for law offices as an expert on pathological gambling.


Yes

This study sought to combine the strengths of prior treatments into a brief, 6 session format of imaginal desensitisation plus motivational interviewing (CBT)


Yes


Yes


Yes


Not reported


Not reported


Not reported


Not reported


Not reported


Yes


No

No follow up


Yes

No mention of psychometric properties, however, instruments used are known to be valid and reliable.


Partial

Standardised tools used. Not aware if outcome assessor was blinded.


Yes

Using previously reported effect sizes from other psychosocial studies of pathological gambling and a two-tailed alpha level of 0.05, a total sample of 68 was required to generate a power of 0.80.


Partial - The test used was appropriate for the type of data (ANCOVA) - Confounding variables were addressed and taken into account - Means and standard deviations were provided - Normality was not mentioned - An intention to treat analysis was performed - The number of dropouts was not reported


Yes

No statistically significant imbalances existed regarding any baseline variable


Not reported


Yes

Intention to treat


Yes


Yes


Yes

Other



Results During the acute 8 week treatment period significantly better results on the PG-YBOCS were observed for the IDMI group. Participants in the IDMI group demonstrated a significantly greater response to the other measures of gambling severity (G-SAS, CGI-S), depression and anxiety symptoms and psychosocial functioning. Author’s conclusions This investigation suggests that IDMI may be effective in the treatment of pathological gambling. As effective treatments for pathological gambling emerge, it becomes increasingly important that physicians and mental healthcare providers screen for pathological gambling in order to provide timely treatment.

Study ID (ie. Thomas 2009) and citation: Hodgins 2001. Hodgins DC, Currie SR, el-Guebaly N. Motivational enhancement and self-help treatments for problem gambling. Journal of consulting and clinical psychology. [Clinical Trial. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2001 Feb;69(1):50-7. Hodgins DC, Currie S, el-Guebaly N, Peden N. Brief motivational treatment for problem gambling: a 24-month follow-up. Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors. [Clinical Trial. Randomized Controlled Trial]. 2004 Sep;18(3):293-6.

Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: Canada

Description of study: randomised controlled trial – level I evidence Patient/population Community sample recruited through media announcements. Mean age=46 (9) and 52% were women. 86%reported that video lottery terminal play (electronic

slot machines was a major problem, 19% casinos, 10% bingo, 4% horse racing, 4 %lotteries, 3% slot machines, 3% card games, 1% speculative investments and 1% games of skill. Quitting was the goal for 84% and 16% wanted to cut back on gambling

N 196 screened. 102 randomised. Setting Community- interview over phone and self help manual Intervention/indicator (a) n=35 Group 1 participants received the self help workbook (based on a cognitive behavioural model) through the mail after a brief telephone interview where

background information was obtained. The self help workbook included self-assessment, goal setting, strategies, maintenance and other resources. (b) n= 32 Group 2 participants received the self help workbook after a motivational style telephone interview. The interview took between 20 and 45 mins to conduct. By using the principles of motivational enhancement therapy they attempted to build a commitment to change. The MI interview was directed by protocol and was conducted by either David C. Hodgins or Shawn R. Currie

Comparison/control (c) n= 35. 1 month waiting list control after brief intake interview. Intake interview consisted of SOGS, brief gambling history and demographic data. Outcomes Days gambled per month, total amount of dollars lost per month and mean amount of dollars lost per gambling day. Inclusion Criteria 18 years and over. Perception of a gambling problem. Willingness to read a short workbook as a major treatment. Willingness to provide follow up data on

gambling. Willingness to provide the name of a collateral to help locate them for follow up interviews. Willingness to provide the name of the same or a different collateral for data validation.

Exclusion Criteria Present involvement in treatment.

Study Validity



No

Research was supported by Health Services grant from the Alberta Heritage Foundation for Medical Research


Yes


Yes


Yes


Yes


Not reported Willing volunteers were randomly assigned to one of three groups ensuring equal numbers of men and women in each.


Not reported


Not reported


Not reported


No The same research assistant who was aware of the assigned condition conducted all initial and follow up interviews.


Yes


Yes

1,3,6 and 12 follow up and 24 month (from Hodgins 2004) follow ups


Yes

SOGS valid and reliable, collateral used to verify participants self report data


Partial

Standardised tools were used, however, outcome assessor was not blinded to intervention group.


No

A post hoc power analysis revealed that the power to uncover group differences was weak.


Yes

- The tests used were appropriate for the type of data - An ANCOVA was performed but the covariate was not mentioned - The means and standard deviations were provided for some of the time points - Normality was addressed and a shifted natural logarithmic transformation was performed where appropriate - The dropout rate was small and an intention to treat and completer analyses was performed


Yes

Preliminary analyses did not uncover any significant differences between the 3 groups on these initial assessment variables.


group 1: 2/35=5.71% , group 2: 1/32=3.13% group 3: 1/35=2.86


Yes

Using an intention to treat approach where the last valid observation was carried forward for missing information. Analysis with the complete data set excluding missing data was also performed.


Yes


Yes


Yes

Other



Results A preliminary repeated measures ANOVA conducted on each of the three outcome variables showed a highly significant time effect, indicating that all three groups showed improvement. For each variable the group receiving MI showed greater improvement than the waiting list control. They gambled fewer days, lost less money and spent less per gambling day. The group receiving the workbook only did not differ significantly from the waiting list control. Author’s conclusions Overall, results support the effectiveness of a brief telephone and mail based treatment for problem gambling.

Study ID (ie. Thomas 2009) and citation: Hodgins 2009. Hodgins DC, Currie SR, Currie G, Fick GH, Hodgins DC, Currie SR, et al. Randomized trial of brief motivational treatments for pathological gamblers: More is not necessarily better. J Consult Clin Psychol. [Randomized Controlled Trial

Research Support, Non-U.S. Gov't]. 2009 Oct;77(5):950-60. Initials of person extracting/appraising data: SM Type of publication: peer reviewed journal article Language of publication: English Country the study was conducted: Canada

Description of study: randomised controlled trial – level I evidence Patient/population 55.4% were female. Community sample recruited through media announcements N N=314 Setting Community- Mail and phone interviews and assessments. Intervention/indicator (a) n=83, brief treatment, These participants received the CBT self-help workbook in the mail after a motivational style interview. The research assistant described

the study, obtained informed consent, conducted an initial telephone assessment with the participant, and informed the individual that a therapist would be calling to discuss his or her problem. The motivational therapist called as soon as possible to conduct the motivational interview (M = 6.2 days, SD = 1.9). These contacts were a mean of 33.7 (11.4) minutes in length. ( b)n=84, brief booster treatment, These participants received the same motivational interview (M = 33.9 min, SD = 10.7, range = 17–73) and self-help workbook as the BT group plus telephone support offered on six occasions over the follow-up period. The therapist contacted the participant 2, 6, 10, 16, 24, and 36 weeks after the initial assessment. These contacts were designed to be booster sessions to reinforce the motivational processes that began in the initial session. Participants received a mean of 4.3 (SD=2) booster calls and these contacts were a mean of 16.3 (9.9) minutes long. A total of 8 therapists conducted the BT and BBT Mis. Training involved directed readings in MI, review of Miller and Rollnick's training tapes and group role playing plus supervision on at least two initial interviews.

Comparison/control (c) n=82, workbook only control, These participants received the self-help workbook via the mail after the telephone assessment interview. There was no therapist contact with these individuals. (d)n=65, 6 week waitlist control, These participants were assigned to a 6-week waitlist control. The research assistant conducted the initial assessment and then informed the individual that there would be a waiting period before the materials could be mailed and that the research assistant would call back in 6 weeks to reassess and provide the workbook. There was also no therapist contact with these participants.

Outcomes Two primary outcome variables were established a priori as: days of gambling and dollars lost gambling. Secondary outcome variables included NODS, Gambling Abstinence Self-efficacy Scale, and the proportion of participants entering treatment.

Inclusion Criteria Inclusion criteria were as follows: 18 years of age or older, perception of a gambling problem, scoring 3 or greater on the Problem Gambling Severity Index of the Canadian Problem Gambling Index (PGSICPGI), gambled in the past month, willingness to read a short book written in English (to ensure reading ability), willing to have telephone contacts recorded, willing to provide follow-up data, willing to provide the name of a collateral to help locate them for follow-up interviews and the name of the same or a different collateral for data validation.

Exclusion Criteria Involved in treatment at present

Study Validity



No

This research was funded by the Canadian Institutes of Health Research and the Ontario Problem Gambling Research Centre.


Yes

The present study was designed to investigate the importance of motivational enhancement as a component of brief interventions and the value of increasing this motivational support over time through follow-up sessions.


Yes


Yes


Yes


Yes Eligible participants were then given an initial interview over the telephone after which they were randomly assigned to one of four groups, which were stratified on gender, age, and problem severity with MINIM, a computer program that uses the method of minimization


Not reported


Not reported


Not reported


Partial The follow-up assessments were conducted by research assistants who were blind to the participants’ assigned groups. A minority of participants revealed their group assignment to the research assistant in the course of a follow-up interview. Research assistants rated themselves as blind to group condition in 91% of interviews. Success of blinding varied significantly according to group, with the most “unblinded” interviews occurring for the BBT group.


Yes


Yes

1 year follow up


Yes

Reliable and valid tools were used and collaterals were successfully interviewed to verify self report data


Partial

Standardised tools were used and the outcome assessor was supposedly blind to intervention group, however, that was only successful in 91% of cases.


Yes

On the basis of a clinical outcome categorization (abstinent, improved, not improved)—for Power = .80, alpha= .05, and 25% difference—60 participants were required in each of the four groups for Hypothesis 1. For Hypothesis 2, to show a clinically meaningful difference of 2 gambling days per month (d = 0.40) and $200 loss per month (d = 0.90) between the BT and BBT groups, 39 and 45 participants, respectively, were required per group (Power = .80, alpha = .05). On the basis of the clinical categorization, to show a difference in improvement rates of 20% among the three groups, 70 participants were required in each group. To allow for attrition, our targeted sample size was, therefore, 66 for the waiting list group and 82 for the WOC, BT, and BBT groups.


Yes

- The tests used were appropriate for the type of data (chi-square, ANCOVA and Mann-Whitney test) - Addressed the issue of normality and where square root transformations were not successful used non-parametric tests - Point estimates and measures of variability are provided - The dropout rate was small. The data that was missing though was handled appropriately


Yes

A varied range of individuals participated in terms of demographics and gambling histories (see Table 1). There were no significant differences between the groups.


For the small number of participants not followed-up at 6 weeks (8.6%), the pre-treatment value was used to estimate the posttreatment value.


Yes

Intention to treat


No

They do not provide the baseline data on the waitlist control group


Yes


Yes

Other


Low



Results

As hypothesized, BT and BBT participants reported less gambling at 6 weeks than those assigned to the control groups. As hypothesized, BT and BBT participants gambled significantly less often over the early follow-up than workbook only participants. However, the workbook only group participants were just as likely to have significantly reduced their losses over the year and to not meet criteria for pathological gambling. The hypothesis that participants in the BBT would show greater improvement throughout the 12-month follow-up was not supported. Generally, the results support the value of offering brief interventions as one option for individuals struggling with gambling problems. Author’s conclusions As hypothesized, brief and brief booster treatment participants reported less gambling at 6 weeks than those assigned to the control groups. Brief and brief booster treatment participants gambled significantly less often over the first 6 months of the follow-up than workbook only participants. However, the workbook only participants were as likely to have significantly reduced their losses over the year and to have not met criteria for pathological gambling. Contrary to the hypothesis, participants in the brief booster treatment group showed no greater improvement than brief treatment participants. These results provide further support for the value of brief motivational treatments for pathological gambling.

Study ID (ie. Thomas 2009) and citation: Hollander 2000. Hollander, E., DeCaria, C. M., Finkell, J. N., Begaz, T., Wong, C. M., & Cartwright, C. (2000). A randomized double-blind fluvoxamine/placebo crossover trial in pathologic gambling. [Clinical Trial. Randomized Controlled Trial. Research Support, Non-U.S. Gov't. Research Support, U.S. Gov't, P.H.S]. Biological psychiatry, 47(9), 813-817.


Description of study: randomised controlled trial – level I evidence Patient/population Outpatient and community sample. All male. Mean age=38.9 (10.3). Preferred types of gambling included sports, horse races, dice games, card games,

lotto/numbers and stocks/commodities N 63 screened to enrol 15 subjects. 2 withdrew during placebo lead in phase therefore 13 were randomised and only 10 qualified as minimum treatment completers

by completing at least 12 weeks. Setting Not reported Intervention/indicator n= 6. Subjects received placebo during phase I and fluvoxamine during phase II. Patients were tapered off their phase I medication at a rate of 50 mg/day

and began to receive phase II medication starting at the beginning of week 8. Comparison/control n=4. Subjects entered 1 week single blind placebo lead in phase to establish a stable baseline, to account for possible early placebo response and to ensure

compliance. Subjects received fluvoxamine for the first 8 weeks (phase I) and a placebo for the following 8 weeks (phase II). Dose: 50mg/day after dinner for week 1, 100mg/day after dinner for week 2 and 150 mg/day for week 3. For the last 5 weeks of each phase the dose was further adjusted in 50-mg increments every weeks with a max of 250mg/day and a minimum of 100mg/day based on therapeutic response and tolerance.

Outcomes PG-YBOCS and PG-CGI Inclusion Criteria DSM-IV diagnosis of PG. SOGS lifetime score of 5 or more. Exclusion Criteria Individuals abusing substances. Past or present schizophrenia, schizoaffective disorder, organic mental syndromes or bipolar disorder type I or II. Those taking

terfenadine, astemizole or cisapride.

Study Validity



Yes

Supported in part by grants from Solvay Pharmaceuticals, the Mount Sinai General Clinical Research Center, National Institute on Drug Abuse and the PBO Foundation.


Yes

The study assessed the efficacy and tolerability of the SSRI fluvoxamine in the treatment of PG


Yes


Yes


Yes


Not reported The remaining 13 were randomly assigned to the two treatment groups.


Not reported


Yes

Double blind study


Yes

Double blind study


Not reported


Yes


No No follow up


Yes

Psychometrics such as inter-rater reliability and convergent validity discussed.


Partial

Standardised tools were used. No mention of blinding outcome assessors


Not reported


No

- The tests used were appropriate for the type of data (ANOVA) - Normality was not addressed - Plotted change in improvement but unclear how this was done and whether it was appropriate. - No point estimates or measures of variability were provided - No confounders were identified or reported - No adjustment was made for multiple testing


Not reported


5/15= 33% Two of the subjects were receiving fluvoxamine, one dropping out due to noncompliance and the other due to an adverse event resulting from concomitant as-occasion requires medication interaction. The non completer receiving the placebo dropped out due to noncompliance.


Yes

10 subjects qualified as minimum treatment completers by completing at least 12 weeks. 2 dropped out during placebo lead in and 3 before week 4.


Yes


Yes

For cross-over studies only To go after ‘Were investigators and care providers blind to treatment allocation?’

Was this intervention suitable for a cross-over study?

Yes

Was the washout period adequate? Not reported Patients were tapered off their phase I medication at a rate of 50 mg/day and began to receive phase II medication starting at the beginning of week 8


Yes

Other



Results Percent improvement on PG-CGI was significantly greater for fluvoxamine than for the placebo. There was a significant overall drug effect on gambling urges and behaviour associated with PG, but also a significant drug 3 phase interaction. Post hoc analysis, treating each phase as a separate trial, demonstrated a significant difference between fluvoxamine and the placebo in the second phase of the trial but not in the first phase. A strong early placebo effect has been identified in impulsive disorders akin to PG and is a phenomenon that needs to be taken into account in studies of PG. Author’s conclusions these findings suggest that fluvoxamine is well tolerated and may be effective in the treatment of PG in an acute trial, and that an early placebo effect in PG treatment appears to diminish over time. To confirm this finding and to determine whether improvement persists over an extended period of time, a longer duration parallel design trial with long term maintenance follow up should be conducted in a larger and more diverse PG population

Study ID (ie. Thomas 2009) and citation: Hollander 2005. Hollander E, Pallanti S, Allen A, Sood E, Baldini Rossi N. Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders? The American journal of psychiatry. [Clinical Trial. Comparative Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't. Research Support, U.S. Gov't, P.H.S]. 2005 Jan;162(1):137-45.


Description of study: randomised controlled trial – level I evidence Patient/population Recruited via local newspaper advertisements. 17 men and 12 women. Experimental group mean age=40 (8.39) years and control group mean age=47.7 (8.08)

years N 88 screened. 40 randomised and 11 dropped out (29 used in analysis) Setting Outpatient Intervention/indicator n= 18. Treatment: Sustained-release lithium. Duration: 10 weeks. Dose: The drug was administered during the first 2 weeks according to a fixed titration schedule

and the subjects' tolerance. For the first 4 days one tablet (300 oral mg) was taken in the evening. For the next 4 days, 2 tablets (300 mg in the morning and 300 mg at 3:00pm) were taken and for the next 6 days 3 tablets were taken (300 mg in the morning and 600 mg in the evening). During the last 4 weeks of the trial, the dose was maintained at a constant level.

Comparison/control n= 22. Treatment: Placebo. Duration: 10 weeks. Dose: same as above. Outcomes Primary gambling efficacy measures included the pathological gambling section of the Yale-Brown Obsessive Compulsive Scale and the Clinical Global Impression

(CGI) pathological gambling improvement scale. At each visit, depressive symptoms were assessed with the 17-item Hamilton Depression Rating Scale, affective instability with the Clinician-Administered Rating Scale for Mania, anxiety symptoms with the Hamilton Anxiety Rating Scale, and impulsivity severity with the Barratt Impulsiveness Scale. Gambling severity was also assessed with the pathological gambling Behavioral Self-Report Scale and the Pathological Gambling 100-mm Visual Analog Craving Scale.

Inclusion Criteria DSM-IV diagnoses of pathological gambling using SCID and SOGS and bipolar spectrum disorder (bipolar II, bipolar disorder not otherwise specified or cyclothymia) assessed using the Mood Disorder Questionnaire (score of 7 or more). Women of childbearing potential or who were less than 2 years postmenopausal were required to use a medically acceptable method of birth control and to have a negative serum pregnancy test before study entry.

Exclusion Criteria Bipolar I disorder. Other major medical illness. Primary diagnosis of schizophrenia, other psychotic disorders, current substance abuse (except nicotine) or other organic mental disorders. Serious suicidal risk or display of significant self-injurious behaviour. Abnormal ECG, liver function, thyroid function or hematological findings. Positive urine drug screen. Focal neurological abnormalities.

Study Validity



Yes

Supported by an investigator-initiated research grant from Solvay Pharmaceuticals Inc. And a grant from the National Institute of Drug Abuse.


Yes

The aim of the present study was to investigate the efficacy and tolerability of sustained-release lithium carbonate in the treatment of bipolar spectrum pathological gambling in a 10-week, double-blind, placebo-controlled parallel trial, the first that we know of to be conducted in this population.


Yes


Yes


Yes


Not reported At the time of enrolment each patient was randomly entered in a parallel fashion


Not reported


Yes

Double blind study


Yes

Double blind study


Not reported


Yes


No

No follow up


Yes

Psychometric properties not reported however measures used have been said to be valid and reliable


Partial

Standardised tools were used. Not aware if outcome assessor was blinded


Not reported

Statistically significant differences were found


Partial - The tests used were appropriate for the type of data - No mention of normality - Missing data was handled appropriately - Mentioned the covariates, but not sure if appropriate seeing as they didn’t report on baseline differences between the conditions


Not reported

Table of baseline but no mention if significantly different or not


lithium: 6/18= 33%

placebo: 5/22= 23%

Eleven subjects dropped out of the study; these were equally likely to come from the treatment as the placebo group (six lithium/five placebo) (p=0.50, Fisher’s exact test). Dropout was unrelated to treatment efficacy, and the reasons for dropout did not differ between the groups: failure to return (five lithium/three placebo), non-adherence to the protocol (two placebo), consent retired (one lithium).


Yes

Intention to treat and completer analyses.


Yes


Yes


Yes

Other


High



Results Pathological gambling patients with bipolar spectrum disorders significantly improved while taking sustained release lithium carbonate compared to placebo on total pathological gambling scores on the Yale-Brown Obsessive Compulsive Scale, including both thoughts/ urges and behavior, as well as on the Clinical Global Impression severity of pathological gambling scale. Affective instability (the Clinician-Administered Rating Scale for Mania score) was also lower in the group treated with sustained-release lithium carbonate compared to placebo. Ten (83%) of 12 completers were rated as responders in the sustained-release lithium group versus five (29%) of 17 in the placebo group. Of note, improvement in gambling severity was significantly correlated with improvement in mania ratings. Author’s conclusions Sustained-release lithium may be an effective treatment in reducing both gambling behavior and affective instability in pathological gamblers with bipolar spectrum disorders. This study highlights the need to identify subgroups of pathological gambling patients with bipolar spectrum conditions because this may have important treatment implications. Thus, further studies in pathological gambling should take such comorbid conditions into account and use appropriate screening instruments to identify pathological gambling subtypes. In addition, there is a need for a longer duration of acute and maintenance treatment studies.

Study ID (ie. Thomas 2009) and citation: Kim 2001. Kim SW, Grant JE, Adson DE, Shin YC. Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling.

Biological psychiatry. [Clinical Trial. Comparative Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2001 Jun;49(11):914-21. Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: America

Description of study: randomised controlled trial – level I evidence Patient/population Community sample. 16 males and 29 females. Naltrexone group mean age= 48 (9.8) years and placebo group mean age= 49.04 (9.58) years. N 83 enrolled and 45 analysed. Setting Not reported Intervention/indicator n=20. Duration: 12 weeks. Treatment: naltrexone. Patients were randomised to either placebo or naltrexone after the 1-week single-blind placebo lead-in.

Naltrexone was started at 25 mg/day for the first two days followed by 50 mg/day for the rest of the week. The dose was then gradually raised until an optimal outcome (clinical judgment) was obtained or the dose reached 250 mg/day, whichever came first. The rate of increase was limited to 50 mg/week. If the dose exceeded 50 mg/day, the dose was divided equally and given twice a day.

Comparison/control n=25. Duration: 12 weeks. Treatment: placebo. Patients were randomised to either placebo or naltrexone after the 1-week single-blind placebo lead-in. The placebo was dispensed in capsules identical to the naltrexone, and each capsule contained an amount of placebo equivalent to 50 mg of naltrexone.

Outcomes Patient rated CGI (PG-CGI-PT), Clinician rated CGI (PG-CGI-MD), G-SAS, HDRS and HARS Inclusion Criteria (1) age 18–75 years, (2) diagnosis of pathologic gambling disorder by DSM-IV, (3) no other current Axis-I diagnosis by the Structured Clinical Interview for DSM-IV

(SCID) (comorbid simple phobia such as height phobia and nicotine dependence were accepted), (4) psychotropic drug-free period of 2 weeks or more (4 weeks or more for fluoxetine, (5) the South Oaks Gambling Screen (SOGS) scale score of 5 or more, (6) the Hamilton Depression Rating Scale (HDRS 17-item) score of 16 or less, (7) the Hamilton Anxiety Scale (HARS) score less than 16, (8) normal complete blood count (CBC) and liver function tests (LFTs), (9) negative pregnancy test in female subjects of childbearing potential, (10) agreement to use contraception during the course of the study if a female subject of childbearing potential and (11) signed informed consent after complete description of the study.

Exclusion Criteria (1) subjects attending Gamblers Anonymous or receiving outpatient gambling treatment, (2) subjects receiving group or individual therapy, (3) history of clinically significant cardiac, hepatic, renal, neurologic or pulmonary disease, (4) prior naltrexone exposure or known hypersensitivity to naltrexone, (5) SCID diagnosis of drug or alcohol abuse within 3 months, (6) severe personality disorder (e.g., borderline personality disorder, antisocial personality disorder) assessed by clinical interview and (7) pregnant patients or nursing mothers. Nonsteroidal analgesics use was added as an exclusionary criterion during the early phase of the study based on clinical observations of a possible nonsteroidal analgesic and naltrexone interaction

Study Validity



No

Supported in part by a grant from the National Center for Responsible Gaming (NCRG).


Yes

We hypothesized that naltrexone would dampen the urges and pleasures associated with gambling but at a dose higher than 50 mg/day.


Yes


Yes


Yes


Not reported


Not reported


Yes

Double blind study


Yes

Double blind and the higher dose in the placebo group suggests that investigators who were blind to the study drug continued to up-titrate the placebo dose because of a lack of response within this group.


Not reported


Yes


No

No follow up


Yes

Used valid and reliable measures in the CGI and addressed the psychometric properties of the G-SAS


Partial

Standardised tools were used. Not aware if outcome assessors were blinded.


Not reported

Statistically significant differences were found


Partial

- The test used was appropriate for the type of data, however, the reporting of the results was very unclear (mixed effects linear regression analyses) - No mention of normality - Some point estimates were provided - No comparisons between the completers and the non-completers


Yes

No significant group differences were found for any demographic and gambling symptom variables.


38/83=46% overall dropout rate.

No data on dropout in each arm. Original group numbers were not reported. Thirty-eight of the 83 subjects enrolled were terminated before being treated with 100 mg/day of naltrexone for at least 2 weeks. Reasons for termination were: abnormal hepatic transaminase levels at baseline visit (n = 5), improvement of 50% or more on the G-SAS score during the first week placebo lead-in period (placebo responders) (n = 22), lost to follow-up before visit six (n = 6), became pregnant during the study (n = 1), developed intolerable side effects (naltrexone group) (n = 2), unable to keep the study schedule (n = 2).


Yes

The data from the patients who were terminated after visit six, which corresponds to naltrexone 100 mg/day for at least 2 weeks, were carried forward. Including only the subjects who were treated with 100 mg/day or more was defined by the a priori hypothesis and supported by our earlier clinical findings


Partial

Don't mention the endpoint data for the HDRS and HARS


Yes


Yes

Other



Results The naltrexone group showed significant improvement over the placebo group in all measures. Weekly symptom improvement by naltrexone group was statistically significant compared with placebo group on all three outcome measures: PG-CGI-PT, PG-CGI-MD and G-SAS. Analysis also shows a significant time effect suggesting that there is a significant placebo effect in the drug treatment of pathologic gambling. For those who had moderate or higher level of urges (> 4 on G-SAS items score), the symptom decrease is more pronounced in the naltrexone group (n = 17) than the placebo group (n = 19; z = -2.045, p = .041). When lower than moderate level of urges are included (all urge scores), the outcome is not as impressive (z = 21.824, p = .068). Author’s conclusions Results suggest that naltrexone is effective in reducing the symptoms of pathologic gambling. Until further studies corroborate the present findings, our report should be interpreted cautiously.

Study ID (ie. Thomas 2009) and citation: Kim 2002. Kim SW, Grant JE, Adson DE, Shin YC, Zaninelli R. A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling. The Journal of clinical psychiatry. [Clinical Trial. Comparative Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2002 Jun;63(6):501-7.


Description of study: randomised controlled trial – level I evidence Patient/population 15 males, 30 females, 96% white, 4% African American, community and referrals. Paroxetine group mean age=49.3(10.8) years and placebo group mean age=49.3

(10.1) years. Main form of gambling included slot machines followed by bingo, blackjack, sporting events, dice, horse/dog track and pull tabs. N 133 screened, 86 potential patients made appointments for interviews, 71 kept their appointments, 53 met inclusion criteria and 45 were randomised after 1

week placebo run-in phase. Setting Not reported Intervention/indicator n=23. Treatment: paroxetine. Duration: 1 week placebo run in phase and the study medication was given for 8 weeks. Dose: The initial paroxetine dosage of

20mg/day could be increased gradually to a maximum of 60 mg/day in increments of no more than 10mg/week. Comparison/control n=22. Treatment: placebo. Duration: 1 week placebo run in phase and 8 weeks of double blind treatment Outcomes G-SAS, PG-CGI clinician and patient rated, HAM-D and HAM-A Inclusion Criteria 18-65 years of age. DSM-IV criteria for pathological gambling. Score of 5 or more on SOGS. Psychotropic medications were discontinued at least 4 weeks before

study start. Exclusion Criteria Diagnosis of other Axis I disorder as determined by SCID. Score greater than 18 on HAM-A or HAM-D. Concomitant psychotropic medication. Undergoing

individual or group psychotherapy or participation in Gamblers Anonymous. Untreated co-existing medical condition. Women of childbearing potential who did not practice a reliable method of contraception.

Study Validity



Yes

Financial support from GlaxoSmithKline Pharmaceuticals


Yes

We conducted a double blind, placebo controlled study to evaluate the efficacy and safety of paroxetine in the treatment of pathological gambling.


Yes


Yes


Yes


Not reported Patients were randomly assigned.


Not reported


Yes

Double blind study


Yes

Double blind study


Not reported


Yes


No

No follow up


Yes

Outcome measures used were reliable and valid. G-SAS reliability and validity addressed. Used patient and clinician rated CGI to corroborate


Partial

Standardised tools used. Not aware if outcome assessors were blinded


Not reported

Statistically significant results were found


No

- It was unclear which tests were used for each of the outcomes. - Claimed that ANOVA was performed, however, no F values were provided, t values were given instead. - Normality was not addressed. - Mean and SD's at baseline were provided but for other time points were only provided in a figure. Potential confounders were addressed. - No adjustment was made for multiple testing. - Intention to treat and completer analyses were performed but it was not clearly stated, it had to be inferred.


Yes

At baseline the treatment groups were very similar with respect to mean age, mean SOGS and G-SAS scores, and mean HAM-A and HAM-D scores. The patients in the placebo group had lost on average 10% more of their weekly income than the paroxetine patients during the week before study start, but this difference was not statistically significant. There was a greater proportion of women in the placebo group. Since the severity of pathological gambling symptoms at baseline was similar for men and women it is assumed that this difference did not affect the analysis of the outcome measures.


Paroxetine:3/23=13% Placebo: 1/22=5%

Reasons for dropout included unable to comply with study schedule and discontinued study due to side effects.


Yes

The intention to treat population comprised all patients who were randomly assigned to double-blind study medication and for whom at least 1 post-baseline efficacy assessment was available.


No

Results from the G-SAS, PG-CGI-MD, PG-CGI-PT, HAM-A and HAM-D were addressed, however, they were presented in figures and graphs. Results of the ANOVA were not reported.


Yes


Yes

Other



Results At all assessment time points, the reduction in the G-SAS total score in the paroxetine group was greater than in the placebo group, with the differences between treatment groups being statistically significant at week 1, week 3, and weeks 6 through 8. In the LOCF dataset the reduction in the mean G-SAS gambling urge subscale score was numerically superior in the paroxetine group compared with the placebo group, but the differences were not statistically significantly greater. Among those patients completing the 8 week treatment, however, the reduction in the G-SAS gambling urge subscale was significantly greater in the paroxetine group than in the placebo group at week 1 and at weeks 6 through 8. Self-rated improvement as measured by the PG-CGI-PT was also significantly greater in the paroxetine than in the placebo group at weeks 6 through 8 and similarly at weeks 7 and 8 from the clinician’s perspective. The difference between the two groups regarding the percentage of weekly income lost by gambling in the previous week was not statistically significant. Author’s conclusions The results of this trial indicate that paroxetine may be effective in the treatment of pathological gambling. There were no unexpected side effects from this treatment. However, additional studies with larger patient samples and a longer treatment phase are required to establish conclusively the efficacy and safety of paroxetine for this indication.

Study ID (ie. Thomas 2009) and citation: Korman 2008. Korman L, Collins J, Littman-Sharp N, Skinner W, McMain S, Mercado V. Randomized control trial of an integrated therapy for comorbid anger and gambling. Psychotherapy Research. 2008;18(4):454-65.


Description of study: randomised controlled trial – level I evidence Patient/population 36 males and 6 females. Mean age=47.6 (11.13) years. 64.3% reported their primary ethnocultural affiliation being something other than Canadian, British or

French (CANADA). Outpatient and community sample. N 163 screened, 136 met criteria and were booked for assessment, 84 were assessed and 42 were randomised Setting Outpatient addiction and mental health treatment center Intervention/indicator n=20. Duration: 14 weeks. Treatment: anger and addiction treatment (A&A) targeting anger, gambling and substance use. The integrated A&A treatment involved

individual sessions that combined functional analyses, skills training, exposure, response prevention, and rehearsal to concurrently treat problem anger, gambling, and substance use. The A&A condition combined a modified DBT approach with a specific skill set designed to address anger and addiction problems. The A&A treatment was delivered in individual sessions and was designed to include two sessions devoted to treatment engagement and orientation followed by 12 individual sessions. For each week’s session, participants recorded anger, gambling, and substance use behaviours they engaged in during the preceding week, noting skills use and emotions they experienced each day. The first 30 to 40 minutes of each treatment session was devoted to functional analyses of anger, gambling, and substance use behaviours reported during the preceding week. The last 20 to 30 minutes of each treatment session were spent teaching participants appropriate skills and, as indicated, engaging them in skills rehearsal and exposure interventions. There were four therapists in the A & A condition (mean of 6.5 years of formal training and five in the TAU condition (mean of 4.5 years of formal training).

Comparison/control n=22. Duration: 14 week Treatment: treatment as usual (TAU) targeting gambling and substance use. The TAU was a well-established specialised outpatient gambling and substance use treatment provided to treatment-seeking problem gamblers (with or without substance use disorders). This treatment used an eclectic, non-manualised approach that included CBT relapse prevention strategies to help participants identify and correct distorted cognitions associated with problem gambling and identify stimulus control and other relapse prevention procedures to minimize gambling and substance use behaviours (e.g., avoiding gambling and substance use cues). The TAU consisted of individual sessions of variable duration and frequency as determined by the TAU therapist based on clients’ needs.

Outcomes Canadian Problem Gambling Inventory (CPGI) which yields a Problem Gambling Severity Index (PGSI). Drug History Questionnaire. State-Trait Anger Expression Inventory (STAXI). Working Alliance Inventory client short form (WAI-C).

Inclusion Criteria Score of 8 or more on Problem Gambling Severity Index. Exclusion Criteria Deny concern about anger. Severe mental illness. Criminal charges pending. Anger score lower than 60th percentile compared to adult norms. High psychopathy

score.

Study Validity



No

This study was funded by a grant from the Ontario Problem Gambling Research Centre


Yes

This study sought to examine the efficacy of a treatment for these co-morbid problems that primarily targeted problems related to emotion dysregulation.


Yes


Yes


Yes


Yes Randomisation was stratified with substance dependence as the stratified variable to ensure that substance use severity was comparable in both treatment conditions. A computerised stratified randomisation program was used to assign participants to conditions. In addition, the person who determined eligibility for participation in the study was different from the person who generated the allocation sequence.


Yes A computerised stratified randomisation program was used to assign participants to conditions. In addition, the person who determined eligibility for participation in the study was different from the person who generated the allocation sequence.


No

Not possible


No Not possible


No To minimise any possible bias all outcome measures were collected via participant entered self report.


Yes


No

3 month follow up


Yes

The psychometric properties of all the measures used were addressed and found that they all had moderate to high psychometric properties


No Even though standardised tools were used outcomes were assessed by the patients themselves


No

Although the sample size of participants who attended treatment sessions resulted in insufficient power for meaningful statistical analyses, the patterns of change observed among participants in the intention-to-treat sample were similar to those observed among participants who attended treatment. Therefore, the observed treatment differences do not appear to be an artefact of group differences in the number of participants who did not attend any sessions.


Yes

- The tests used were appropriate for the type of data (chi-square and multivariate general linear modelling) - Normality was addressed and where required log transformations were performed - Point estimates and measures of variability were provided - Missing data was handled appropriately


Yes

There were no significant differences at baseline between groups for participant.


Treatment: 4/20= 20% Control: 3/22=14%


Yes

This study used an intention-to-treat design in which all randomised participants were followed in the same manner to be assessed regardless of treatment status


Yes


Yes


Yes

Other

What is the overall risk of bias? Moderate Moderate - Some of the criteria have been fulfilled and those criteria that have not been fulfilled may affect the conclusions of the study.


Results The results of the present study provide preliminary evidence for the benefit of an integrated approach for treating comorbid anger, gambling, and substance use problems. To our knowledge, this is one of the first randomised control trials evaluating an integrated treatment for anger, gambling, and substance use problems. In both the A&A and the TAU conditions, there were significant reductions in anger and gambling over the course of treatment. However, unlike the A&A condition, there were no reductions in substance use in the TAU condition. As hypothesized, participants in the integrated A&A condition showed significant reductions in anger, gambling, and substance use in comparison to those in the TAU. The reductions in gambling and substance use observed in the A&A condition were both statistically and clinically meaningful. Participants in this condition reported gambling 84.9% of their income at baseline but only 5.3% of their income at T3. None of the participants randomised to the A&A condition met criteria for problem gambling at T3. In contrast, the reductions in gambling observed in the TAU were more modest. Reductions in anger were found for both the A&A and TAU conditions, with greater reductions found in the A&A condition. Reductions in reported substance use among participants in the A&A condition were also substantial: A&A participants reported substance use on 30 of the last 90 days at T1 and on 7.75 of the last 90 days at T3. In contrast, participants in the TAU did not reduce their substance use from T1 to T3. Author’s conclusions

This study provides preliminary evidence supporting the effectiveness of an integrated emotion-oriented approach to treat co-morbid anger, gambling, and substance use problems. The results of this study suggest that it is important to screen gambling clients for the presence of co-morbid anger and substance use problems. When present, anger and substance use problems need to be addressed concurrently in gambling treatment to optimize treatment outcomes. We also consider it important to assess the functional relationships among anger, gambling, and substance use. Although this study focused specifically on gamblers who had co-morbid anger problems, future research is needed to evaluate whether emotion-oriented interventions are also effective for non-angry problem gamblers, gamblers who have co-morbid depression and anxiety, and angry individuals with other co-morbid addictions.

Study ID (ie. Thomas 2009) and citation: Ladouceur 2001. Ladouceur R, Sylvain C, Boutin C, Lachance S, Doucet C, Leblond J, et al. Cognitive treatment of pathological gambling. The Journal of nervous and mental disease. [Clinical Trial. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2001 Nov;189(11):774-80.


Description of study: randomised controlled trial – level I evidence Patient/population Community and referral sample. Most participants were Caucasians born into Catholic families. 52 males and 11 females. Mean age (of 35 participants who

completed treatment) = 40.8 (10.2). Mean age (29 control group)= 43.4(10.2). 85% reported having problems with gambling on machines, cards (28.3%), horse races (15%), sports (13.3%), blackjack (13.3%), bingo (11.7%), skill games (10%) and keno (10%).

N 217 participants were invited to therapy for a semistructured intake interview and 88 were randomised. 7 participants from the waitlist control undertook the treatment, therefore 66 gamblers began treatment, 35 completed the full program and 31 dropped out.

Setting Was conducted in the Centre Quebecois d'Excellence pour le Traitement et la Prevention du Jeu granted from Loto-Quebec Intervention/indicator n=35. Treatment: CBT. Treatment was administered on an individual basis with one weekly session lasting 60 minutes each for a maximum of 20 sessions.

Treatment included cognitive correction and relapse prevention. Received an average of 11.03 (5.25) hours of treatment. Three experienced cognitive therapists administered the treatment (licensed psychologists). They have treated over 25 pathological gamblers each. They were supervised by the first author, a psychologist with 20 years experience in CBT.

Comparison/control n=29. Treatment: wait-list control. After evaluation, participants in the control group were contacted and told that their name would be placed on a waiting list. Participants were offered treatment after the 3 months waiting period where post-test evaluation was conducted. No other instructions concerning treatment were delivered.

Outcomes DSM-IV criteria met for a diagnosis of pathological gambling were assessed by clinical interview and the SOGS. Participants were rated on a scale of 0-10 on the extent of their belief that they could refrain from gambling in personally relevant high risk situations. Participants were rated on a scale of 0-100 on their perception of control over their gambling problem. Participants indicated on a scale of 0-10 their desire to gamble. SOGS. Participants indicated the number of gambling sessions, number of hours spent gambling and the total amount of money they had spent on gambling during the previous week.

Inclusion Criteria Primary diagnosis of pathological gambling (DSM-IV). Willing to undergo randomisation. Exclusion Criteria Evidence of immediate suicidal intent. Evidence of current or past schizophrenia, bipolar disorder or organic mental disorder.

Study Validity



No

This work was supported by grants from the National Council on Responsible Gaming


Yes

The present study evaluated the efficacy of a cognitive intervention specifically base on the correction of the erroneous perceptions of randomness reported by gamblers.


Yes


Yes


Yes


Not reported


Not reported


Not reported


Not reported


Not reported


Yes


Yes

6 and 12 month follow up


Partial

The SOGS is a validated and reliable tool, however, the psychometric properties of the scales used are unknown.


Partial

Only some standardised tools were used. Not aware if the outcome assessors were blinded.


Not reported

Statistically significant group differences were found


Partial

- Analysis was mostly planned a priori, there were some post hoc tests - Normality was tested and a parametric MANOVA and non-parametric ANOVA's were performed, as well as Wilcoxon and Fishers exact tests. - Means and SD's were provided. - No subgroups were analysed. - No confounders were identified. - Adjusted for multiple testing. - Missing data was not handled appropriately as there was a fairly high drop-out rate and no intention to treat analyses was performed. No comparison between the dropout and completers was mentioned either.


Yes

A MANOVA revealed no significant differences between the treatment and control groups on the first four dependent variables at pre-test. There were no significant differences for number of gambling sessions, number of hours spent gambling or amount of money bet for the week.


31/66=47%. 6 month follow up: 4/35=11%. 12 month follow up: 3/31=10%

A gambler was considered a dropout if he or she stopped treatment anytime after the third session.


No

Those who dropped out were not included in the analyses


Yes


Yes


Yes

Other



Results The results showed that the treatment and control group means differed significantly at post-test for all four variables. Participants in the treatment group met fewer diagnostic criteria and reported less desire to gamble. They also reported a significantly higher perception of control and self-efficacy. Participants in the treatment group also gambled significantly less often than control participants at post-test. Participants of the treatment group spent less time gambling at post-test. Author’s conclusions In conclusion the controlled study shows the effectiveness of a cognitive treatment for pathological gamblers targeting the notion of randomness. Furthermore, results proved to be both statistically and clinically significant.

Study ID (ie. Thomas 2009) and citation: Ladouceur 2003. Ladouceur R, Sylvain C, Boutin C, Lachance S, Doucet C, Leblond J. Group therapy for pathological gamblers: a cognitive approach. Behaviour research and therapy. [Clinical Trial. Randomized Controlled Trial]. 2003 May;41(5):587-96.

Initials of person extracting/appraising data: SM Type of publication: peer reviewed journal article Language of publication: English Country the study was conducted: Canada

Description of study: randomised controlled trial – level I evidence Patient/population 46 engaged in group treatment. 34 participants completed treatment, 25 males and 9 females with a mean age of 42.56 (10.48). There were 25 participants in the

control group, 21 males and 4 females with a mean age of 44.56 (10.7). Most participants were Caucasians with a Catholic background. N 46 engaged in group treatment. 34 completed treatment. 25 in control group. Setting Not reported Intervention/indicator n=34. Treatment: Group cognitive therapy. Treatment was administered on a group basis, with 10 weekly sessions lasting 120 minutes. Treatment included

cognitive correction and relapse prevention. Five experienced cognitive therapists administered the treatment. Each one has treated many pathological gamblers. Comparison/control n=25. Treatment: wait list control. At intake, all participants were informed that because of random assignment to immediate or delayed treatment, there was a

possibility that they would not receive treatment immediately. Following evaluation, participants in the control group were contacted and told that their name would be placed on a waiting list. Participants were offered treatment after the 4 month waiting period, when post-test evaluation was conducted. No other instruction concerning treatment was delivered.

Outcomes 1. DSM-IV: The number of DSM-IV criteria met for a diagnosis of pathological gambling were assessed through a clinical interview (score 0–10). A score of 5 or more indicates pathological gambling. 2. Self-efficacy perception: After describing three idiosyncratic high-risk situations, participants rated the extent of their belief that they could refrain from gambling in these situations on a 0–10 scale. 3. Perception of control: Participants rated their perception of control over their gambling problem on a scale of 0–100. 4. Desire to gamble: Participants indicated their desire to gamble on a 0–10 scale. 5. Frequency of gambling: Participants indicated (a) the number of gambling sessions, (b) the number of hours spent gambling, and (c) the total amount of money they had spent on gambling during the previous week.

Inclusion Criteria Primary diagnosis of pathological gambling. Willing to undergo randomisation. Exclusion Criteria Evidence of current or past schizophrenia, bipolar disorder or organic mental disorder.

Study Validity



Not reported


Yes

The present study evaluated the efficacy of a cognitive intervention, delivered in a group format, which is specifically based on the correction of the erroneous perceptions of randomness reported by gamblers. It was hypothesized that the correction of erroneously perceived links between random events in gambling situations would significantly reduce gambling behavior, compared to the wait-list control group that was not expected to show any improvement. The maintenance of therapeutic gains was evaluated at 6, 12, and 24 months.


Yes


Yes


Yes


Not reported


Not reported


Not reported


Not reported


Not reported


Yes


Yes

6, 12 and 24 month follow up


Partial

The SOGS is a validated and reliable tool, however, the psychometric properties of the scales used are unknown.


Partial

Only some standardised tools were used. Not aware of whether the outcome assessors were blinded.


Not reported

significant differences were found


Partial

- A MANOVA and non-parametric ANOVA were used and were appropriate. - Normality was checked. - Means and SD's were provided for each group at each time point. - No potential confounders were addressed. - There was an adjustment for multiple testing. - Missing data was not handled appropriately, only completers were analysed and no information on dropouts for each group or comparisons of the dropouts were provided.


Yes

A multivariate analysis of variance (MANOVA) revealed no significant differences between the treatment and control groups on the first four dependent variables at pre-test. Frequency of gambling scores were not normally distributed and revealed a large variability. Therefore, they were analysed separately using non-parametric analyses of variance (ANOVAs; PROC CATMOD; SAS Institute, 1989). There were no significant differences in the number of gambling sessions, number of hours spent gambling, or the amount of money spent gambling over the past week.


26% dropped out before the third session. 6 month follow up: 7/34. 12 month follow up: 8/34. 24 month follow up: 12/34


No

Those who dropped out were not included in the analysis.


No

Doesn’t report the results on the frequency of gambling variables


Yes


Yes

Other



Results Tests of simple effects showed that the treatment and control group means differed significantly at post-test for all three variables. Participants in the treatment group met fewer diagnostic criteria. They also reported significantly higher perception of control and self-efficacy. However, the desire to gamble was not significantly reduced when the Bonferroni correction was taken into consideration. Non-parametric repeated measures ANOVAs were performed on the three variables measuring frequency of gambling. Results revealed no significant Group × Time interaction effect for these variables. Author’s conclusions In conclusion, this controlled study shows the effectiveness of a cognitive treatment for pathological gamblers in a group format that targets the notion of randomness. Furthermore, results proved to be both statistically and clinically significant.

Study ID (ie. Thomas 2009) and citation: McElroy 2008. McElroy SL, Nelson EB, Welge JA, Kaehler L, Keck Jr. PE. Olanzapine in the treatment of pathological gambling: A negative randomized placebo-controlled trial. Journal of Clinical Psychiatry. 2008;69(3):433-40.


Description of study: randomised controlled trial – level I evidence Patient/population Community recruited. 18 males and 24 females. 35 of the participants were white and 7 African American. Olanzapine group mean age= 51.5 (11.2) and placebo

group mean age=46.8 (8.2) N 52 screened. 42 randomised. Setting Outpatient Intervention/indicator n=21. Duration: 12 weeks. Treatment: olanzapine. Dose: Olanzapine was begun at 2.5mg/day for the first 7 days. The dosage could then, as tolerated, by 2.5

mg/day every 7 days to a maximum of 15mg/day. Study medication could be reduced to a minimum of 2.5mg/day because of bothersome side effects at any time during the 12 week treatment period. Subjects were instructed to take their entire daily dose of study medication in the evening. However, subjects could take half of the daily dose in the morning. Same 3 phases and evaluation process. The mean (SD) olanzapine daily dose at endpoint evaluation was 8.9 (5.2) mg/day.

Comparison/control n=21. Duration: 12 weeks. Treatment: placebo. 3 phases: a 1-4 week screening period, a 12 week double blind treatment period and a 1 week treatment discontinuation period. The screening period included a 1 week single blind placebo run in during which subjects had to display less than or equal to 50% improvement in their screening PG-YBOCS scores in order to be randomised. Subjects were evaluated twice during screening period, after 1,2,3,4,5,6,8,10 and 12 weeks during treatment period and 1 week after study medication discontinuation. Dose: all study medication was in identical 2.5mg tablets supplied in numbered containers and dispensed to subjects according to a predetermined randomisation schedule.

Outcomes Primary outcome measure was the PG-YBOCS. Secondary measures were weekly frequency of gambling episodes (determined from subjects' take home diaries), total weekly hours spent gambling (diaries), Clinical Global Impressions-Severity scale (CGI-S) and CGI improvement scale (CGI-I), HAM-D, Young Mania Rating Scale (YMRS), Global Assessment of Functioning scale (GAF). Categorical responder criteria at treatment termination was defined 2 ways: as having a CGI-I pathological gambling score of 1 or 2, equaling "much" or "very much" and having a 35 % or greater reduction in the PG-YBOCS total score compared with baseline.

Inclusion Criteria Enrolled if male or female aged 18-65 years. Met DSM-IV-TR criteria for pathological gambling. SOGS score of 5 or higher. Exclusion Criteria Ever had psychotic symptoms or met criteria for a psychotic disorder by DSM-IV-TR criteria. Had bipolar I disorder. Had a substance use disorder within 1 month of

study entry (except for nicotine related disorder). Had a personality disorder that could interfere with diagnostic assessment, treatment or compliance. Displayed clinically significant suicidality. Had begun any psychological treatment for pathological gambling within 3 months before study entry (except for Gamblers Anonymous). Had a clinically unstable medical illness. Had clinically significant laboratory or electrocardiogram abnormalities. Received psychoactive medication (other than hypnotics) within 2 weeks of study medication initiation. Had a history of hypersensitivity to olanzapine. Women excluded if pregnant, lactating or, if fertile, not practicing a form of medically accepted contraception.

Study Validity



Yes

This study was supported in part by a grant from Eli Lilly (pharmaceutical company). Authors also work with various pharmaceutical companies.


Yes

We conducted a single center, randomised, parallel group, placebo controlled, flexible dose study to assess the efficacy and safety of olanzapine during a 12 week course of treatment in 42 outpatients with pathological gambling


Yes


Yes


Yes


Not reported Randomly assigned in a 1:1 ratio to therapy


Not reported


Yes

Double blind study


Yes

Double blind study


Not reported


Yes


No

Evaluated weekly during treatment and 1 week after study medication discontinuation


Yes

Psychometrically sound measures were used. Psychometric properties not discussed in article though


Partial

Standardised tools used. No mention of blinding outcome assessors


No

The small sample size may have provided insufficient power to detect moderate treatment effects.


Yes

- The tests used were appropriate for the type of data - Normality was addressed and where required transformations were used - Missing data was addressed and handled appropriately - Point estimates and measures of variability were provided


Yes

There were no significant differences between the treatment groups in demographic or clinical variables at baseline.


By week 12 placebo: 6/21=29%, olanzapine: 11/21=52% drop out rate

Reasons for dropout included adverse events, lack of efficacy and difficulties with protocol adherence which included patient choice, lost to follow up and beginning exclusionary medication in olanzapine group and patient choice and lost to follow up in placebo group.


Yes

Intention to treat.


Yes


Yes


Yes

Other

What is the overall risk of bias? High



Results Compared with placebo, olanzapine was associated with a similar rate of reduction in total scores on the PG-YBOCS scale, as well as in gambling episodes/week, hours gambled/week, and Clinical Global Impressions-Severity of Illness scale scores.

Author’s conclusions Olanzapine was not found to be superior to placebo in reducing gambling symptoms, gambling frequency or severity illness. Also it was associatedwith only fair tolerability and a relatively high treatment discontinuation rate.

Study ID (ie. Thomas 2009) and citation: Melville 2004 (Experiment 1). Melville CL, Davis CS, Matzenbacher DL, Clayborne J. Node-link-mapping-enhanced group treatment for pathological

gambling. Addictive behaviors. [Clinical Trial. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2004 Jan;29(1):73-87. Initials of person extracting/appraising data: SM Type of publication: peer reviewed journal article Language of publication: English Country the study was conducted: America

Description of study: randomised controlled trial – level I evidence Patient/population Community sample. 5 males and 8 females. Mapping group mean age=68, nonmapping group mean age=52 and control group mean age=53. The sample was

primarily female (69%), white (85%), married (75%) and employed (90%). The gamblers identified slot machines (62%) or video poker (37%) as their primary gambling activity.

N 20 people were recruited and given the intake interview and 13 were assessed and randomly assigned. Setting Not reported Intervention/indicator (a) n=4. Treatment: mapping group. Duration: 8 weeks. Following the intake assessment, each participant met individually with their counsellor for 30 min. During

this session the counsellor provided a description of the format for the group counselling sessions along with session dates and times. At the end of this session participants also tape-recorded thoughts that occurred during an episode of imagined gambling for use later in treatment. The treatment groups received manual guided treatment based on Melville et al. (2000). The group treatment for pathological gambling developed by Melville et al. (2000) uses node-link mapping techniques to focus 24 h of group counselling in the three topic areas (8 h per topic) identified by Sylvain et al. (1997) as important targets for change. The three topic areas include understanding randomness, problem solving, and relapse prevention. The mapping groups received mapping enhanced counselling. Node-link mapping is a visual representation technique designed to highlight interrelations between thoughts, emotions, actions, and environmental influences. Group sessions were 90 min in length, conducted twice per week for eight consecutive weeks. Counsellors completed a checklist of topic maps to be completed at the end of each session. Each treatment group was conducted by a Master's level counsellor. They were provided with 8 hours of training by the first author.

Comparison/control (b) n=4. Treatment: non-mapping group. Duration: 8 weeks. The non-mapping group received the same treatment content without maps (natural language). For the non-mapping group, the treatment manual was modified to exclude node-link maps. Group sessions were 90 min in length, conducted twice per week for eight consecutive weeks. Counsellors completed a checklist of topics discussed at the end of each session. (c) n=5. Treatment: waitlist control group. Participants assigned to the control group were informed that because of random assignment they were placed on a waiting list. They were also informed that the treatment group to which they had been assigned would begin in 8 weeks.

Outcomes DSM-IV criteria, ability to control scale, ability to refrain scale, desire to gamble scale. Participants also reported the number of times gambled, the number of hours spent gambling, and the number of sessions of Gamblers Anonymous attended (or other treatment for problem gambling) in the past 30 days. Participants were asked ‘‘How much have you spent on gambling in the past 30 days?’.

Inclusion Criteria DSM-IV criteria for pathological gambling and scored in the pathological range (5 or more) on the SOGS. Exclusion Criteria

Study Validity



Not reported


Yes

In the present study, two experiments examined the efficacy of this node-link-mapping enhanced group treatment. Experiment 1 compared the mapping-enhanced group treatment to the same treatment without maps, and to a wait-list control group on measures of pathological gambling. Experiment 2 replicated the mapping and wait-list conditions of Experiment 1 and extended the dependent measures to include co-occurring depression and anxiety.


Yes


Partial



Yes


Not reported


Not reported


Not reported


Yes

Counsellors were blind to the conditions of the experiment.


Yes Assessment personnel were Master's level interns specifically trained and blind to the conditions of the experiment.


Yes


No

6 month follow up


Partial

Even though self report scales were used authors refer to them being used previously by other researchers.


Partial

Outcome assessors were blinded, however, scales and self report data was used.


Not reported

Very small sample size.


No

- MANOVA not appropriate with such a small sample size. -No mention of normality or how missing data was handled. - Mean and standard deviations were provided. - Pre-treatment scores were used as a covariate.


Not reported


Of the 20 gamblers who responded, 7 refused to participate following the intake interview.


Not reported


Yes


Yes


Yes

Other



Results The pathological gamblers exposed to mapping-enhanced group treatment met fewer DSM-IV diagnostic criteria at post-treatment than either the non-mapping group or the control group. The self-rated ability to control gambling and the ability to refrain from gambling increased from pre- to post-treatment for each group. The desire to gamble decreased from pre- to post-treatment for each treatment group, whereas a slight increase was observed for the control group. The size of the changes for these self-ratings was larger for the mapping groups than for either the non-mapping or control groups. These treatment effects were retained at 6-month follow-up. Gambling bout duration decreased from pre- to post-treatment for each group. The size of the decrease was larger for the mapping group than for the non-mapping or control groups. Similarly, expenditure decreased from pre- to post-treatment for each group with larger decreases observed for the mapping group than for the non-mapping or control groups. These treatment effects were retained at 6-month follow-up. Author’s conclusions The node-link-mapping-enhanced group treatment produced improvements in more of the dependent measures of pathological gambling than treatment without maps or an equivalent length waiting period. The results are consistent with previous treatment research with substance abusers.

Study ID (ie. Thomas 2009) and citation: Melville 2004 (Experiment 2). Melville CL, Davis CS, Matzenbacher DL, Clayborne J. Node-link-mapping-enhanced group treatment for pathological gambling. Addictive behaviors. [Clinical Trial. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2004 Jan;29(1):73-87.


Description of study: randomised controlled trial – level I evidence Patient/population 3 males and 16 females. Mapping group mean age = 51 and control group mean age=54. The sample was primarily female (76%), white (89%), married (79%), and

employed (93%). The gamblers identified slot machines (62%) or video poker (38%) as their primary gambling activity. N 28 responded, 19 assessed and randomised Setting Not reported Intervention/indicator n=9. Treatment: node-link mapping. Same as experiment 1. Duration: 8 weeks. Extended the dependent measures to include measures of co-occurring anxiety

and depression. Each treatment group was conducted by a Master's level counsellor. They were provided with 8 hours of training by the first author. Comparison/control n=10. Treatment: wait list control. Same as experiment 1. Duration: 8 weeks Outcomes DSM-IV criteria, ability to control scale, ability to refrain scale, desire to gamble scale. Participants also reported the number of times gambled, the number of

hours spent gambling, and the number of sessions of Gamblers Anonymous attended (or other treatment for problem gambling) in the past 30 days. Participants were asked ‘‘How much have you spent on gambling in the past 30 days?’. Beck Depression Inventory-II and Beck Anxiety Inventory.

Inclusion Criteria DSM-IV criteria for pathological gambling and scored in the pathological range (5 or more) on the SOGS. Exclusion Criteria

Study Validity



Not reported


Yes

In the present study, two experiments examined the efficacy of this node-link-mapping enhanced group treatment. Experiment 1 compared the mapping-enhanced group treatment to the same treatment without maps, and to a wait-list control group on measures of pathological gambling. Experiment 2 replicated the mapping and wait-list conditions of Experiment 1 and extended the dependent measures to include co-occurring depression and anxiety.


Yes


Partial



Yes


Not reported


Not reported


Not reported


Yes

Counsellors were blind to the conditions of the experiment.


Yes Assessment personnel were Master's level interns specifically trained and blind to the conditions of the experiment.


Yes


No

6 month follow up


Partial

Even though self report scales were used authors refer to them being used previously by other researchers. BDI-II and BAI reported to be valid and reliable


Partial

Outcome assessors were blinded, however scales and self report data were used


Not reported

Significant differences were found


No

- MANOVA, ANOVA's and t-tests appropriate for continuous data, however a MANOVA is not appropriate with such a small sample size - No mention of normality - Provide means and standard deviation - No mention of confounding variables or if groups were similar at baseline - Did not mention how missing data was handled.


Not reported


28 gamblers responded and 19 were assessed and randomised. Of the 9 that dropped out, 3 were excluded because they did not meet criteria for pathological gambling and 6 refused to participate following the intake interview.


Not reported


Yes


Yes


Yes

Other



Results The pathological gamblers in Experiment 2 exposed to mapping-enhanced group treatment met fewer DSM-IV diagnostic criteria at post-treatment than the control group. As in Experiment 1, the self-rated ability to control gambling and the ability to refrain from gambling increased for both groups. The size of the increase was larger for the mapping group than for the control group. Desire to gamble decreased from pre- to post-treatment for the mapping group but increased pre- to post-treatment for the control group. In general, treatment effects for the mapping group were retained at 6-month follow-up. Gambling bout duration decreased from pre- to post-treatment for the mapping group, whereas bout duration for the control group increased slightly. Expenditure decreased from pre- to post-treatment for each group. The size of the decrease was larger for the mapping group than for the control group. The treatment effects observed for the mapping group were retained at 6-month follow-up. Depression scores decreased pre- to post-treatment for the mapping group, whereas depression scores for the control group did not change. Likewise, anxiety scores decreased for both the mapping and control groups with larger decreases observed for the mapping group. In general, these treatment effects were retained at 6-month follow-up for the mapping group. Author’s conclusions The node-link-mapping-enhanced group treatment produced improvements in more of the dependent measures of pathological gambling than an equivalent-length waiting period. It also produced larger decreases in co-occurring depression and anxiety than an equivalent-length waiting period. The results are consistent with previous treatment research with substance abusers.

Study ID (ie. Thomas 2009) and citation: Milton 2002. Milton S, Crino R, Hunt C, Prosser E. The effect of compliance-improving interventions on the cognitive-behavioural treatment of pathological gambling. Journal of gambling studies / co-sponsored by the National Council on Problem Gambling and Institute for the Study of Gambling and Commercial Gaming. [Clinical Trial. Comparative Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2002;18(2):207-29.

Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: Australia

Description of study: randomised controlled trial – level I evidence Patient/population Participants were referred by health professionals, recruited through advertisements or referred by a state-wide, government sponsored referral service. 29 male

and 11 female. Mean age= 37.6. Thirty experienced most of their problems as a result of playing poker machines, six were off-course horse racing gamblers, two played casino blackjack, one gambled on sports and one gambled on a lotto type game that allows frequent play (Keno).

N 47 assessed and 40 randomised. Setting University based gambling treatment clinic. Intervention/indicator n=20. Treatment: CBT and compliance improving interventions. Duration: 14 weeks. Participants received a range of compliance-improving interventions, in

addition to the treatment administered in the CBT condition. The compliance-improving interventions were designed to enhance and maintain the participant’s motivation to change their gambling behaviour throughout treatment with the goal of ensuring the treatment program was completed. There were eight specific interventions: 1. When the appointment was made, participants were positively reinforced by the clinician, receiving verbal praise and encouragement for recognising that gambling was a problem and for doing something about it. A letter confirming the appointment repeated this praise and encouragement. 2. At the end of the assessment session, participants were given a positive prognosis and were again praised for making the decision to change their gambling behaviour. 3. The importance of attending each session in order for positive outcomes to be achieved was emphasised in the assessment session. Participants were informed that if they missed one session, the clinician would contact them to encourage them to return for treatment. For each participant, this would only be done on one occasion. If a second appointment was missed, the participant would only be re-contacted nine months later for a follow-up session. 4. After the assessment session, participants were sent a short letter confirming their next appointment. The letter also repeated the positive prognosis, praise, and encouragement given at the end of the assessment session. 5. Assessment results were fed back to participants using a number of techniques adapted from the substance use disorder field. 6. Participants were asked to complete a decisional balance sheet between every session. 7. Participants were assisted in identifying and removing barriers that inhibited or discouraged change. Problem solving techniques were applied specifically to these issues 8. Throughout the treatment, the therapist focussed on reinforcing participants’ self-efficacy in order to increase their belief in their ability to overcome obstacles and achieve treatment goals. In 100% of cases where participants finished the treatment, all of the material from the manuals was covered. Additionally, stringent efforts were made to ensure that participants in the CBT group did not receive any compliance-improving interventions from the therapist. These participants received no letters or phone calls if they dropped out and were not given a positive prognosis or feedback from the assessment session. Recording of sessions was not conducted due to the confidentiality concerns of participants.

Comparison/control n=20. Treatment: CBT. After contacting the clinic, participants were sent a standard letter confirming their appointment. Once they were assessed, participants were informed that they would receive seven treatment sessions and would be re-contacted nine months after the final session for a follow-up session. Outpatient treatment was provided, consisting of four components: psychoeducation, cognitive restructuring, problem solving skills and relapse prevention.

Outcomes Treatment outcomes: Structured Clinical Interview for Pathological Gambling (SCIP), SOGS (6 month version) and Percentage of net monthly income lost gambling in the past month (YPMG). The following measures were used to predict compliance and outcome: BDI, STAI, Alcohol Use Disorders Identification Test (AUDIT), Drug Abuse Screening Test (DAST), Contemplation Ladder and Problem Gambling Duration (PGD).

Inclusion Criteria Not reported

Exclusion Criteria Not meeting diagnosis, facing sentencing and antipsychotic medication

Study Validity



No

Financial assistance for this Project was provided by the New South Wales State Government from the Casino Community Benefit Fund.


Yes

There are two objectives to the current exploratory study. The first objective is to test the hypothesis that the addition of compliance improving interventions to the cognitive-behavioural treatment for pathological gambling will result in significantly higher treatment completion levels. A further hypothesis is that the pathological gamblers receiving the additional compliance-improving intervention will achieve greater therapeutic gains at nine-month follow-up than those receiving the cognitive behavioural treatment alone. The second objective of the study is exploratory in nature, attempting to identify factors that may predict treatment compliance and treatment outcome. It is hypothesised that higher levels of comorbidity, specifically anxiety, depression and substance use, will result in poorer treatment compliance and outcome. It is also hypothesised that longer problem gambling duration and lower levels of motivation to change will also result in poorer compliance and outcome.


Yes


Partial

Mentioned some exclusion criteria in text but didn’t seem to be determined a priori


Yes

The criteria that were mentioned were appropriate


Yes On contacting the clinic, participants were assigned the next number from a random number table. This number was used to randomly assign the participant to either the cognitive-behavioural treatment condition (odd numbers, CBT) or the cognitive-behavioural treatment combined with compliance-improving interventions condition (even numbers, CBT+CI).


Not reported


Not reported


Not reported


Not reported


Yes


No

9 month follow up


Yes

Psychometric properties not mentioned, however, measures seem to be valid and reliable


Partial

Standardised tools were used. No mention of blinding


Yes

The time restrictions placed on the study meant that the maximum sample size for each treatment group was 20 participants. Assuming an alpha rate of .05 and a compliance rate for the cognitive behavioural treatment of 65%, the sample size would provide enough power (at 1-beta = .80) to allow the detection of an increased compliance rate of 30% in the compliance-improving condition. DISCUSSION: However, these analyses produced a range of very low power figures, making it difficult for the study to reject the null hypotheses. The improvements attributed to the compliance-improving interventions at post-treatment were not present at follow-up. Although the power is low, an examination of the treatment means in Table 3 does not support a replication of the study with an increased sample size.


Partial

- Several tests, such as, logistic regression and repeated measures ANOVA were performed and seemed to be appropriate. - Normality was checked and where required non-parametric tests were used. -Some obscure tests were used, however, not all provided reasons for their use or references. - Means and standard deviations were provided for each time. - No adjustment was made for multiple testing. - An intention to treat sample was used, however, there were very high dropout rates, with no comparisons between the completers and the dropouts.


Yes

There were no significant differences between treatment groups on age, gambling type, gender, or income.


CBT=13/20=65%. CBT+CI=7/20=35%

A significantly higher proportion of participants in the CBT + CI condition completed treatment compared to the CBT condition.


Yes

Intention to treat


Yes


Yes


Yes

Other


Moderate



Results The study found that compliance-improving interventions did significantly improve treatment completion rates and that co-morbid problem drinking, co-morbid drug use and disorder duration predicted poor compliance. Compliance-improving interventions produced higher levels of clinically significant change at post-treatment compared to the cognitive behavioural intervention. However, this difference was no longer evident at nine-month follow-up. Of the covariates examined in the study, co-morbid problem drinking predicted poor treatment outcome. Author’s conclusions Compliance-improving interventions significantly reduced dropout rates, resulting in superior outcomes at post-treatment compared to the cognitive behavioural treatment alone. At 9-month follow-up, there was no difference in outcome between treatments, although both produced clinically significant change. Co-morbid problem drinking, drug use, and problem gambling duration predicted poor compliance. Poor outcome was predicted by co-morbid problem drinking. The clinical implications of these results are discussed in light of the exploratory nature of the study and the need for future research to address compliance, outcome, and co-morbidity issues.

Study ID (ie. Thomas 2009) and citation: Petry 2006. Petry NM, Ammerman Y, Bohl J, Doersch A, Gay H, Kadden R, et al. Cognitive-behavioral therapy for pathological gamblers. Journal of consulting and clinical psychology. [Randomized Controlled Trial. Research Support, N.I.H., Extramural]. 2006 Jun;74(3):555-67.


Description of study: randomised controlled trial – level I evidence Patient/population 104 females and 127 males. GA referral mean age=44.4(11.7), CB workbook mean age=44.3(9.4) and CB therapy mean age=45.8(11.6). 20 African Americans, 195

European Americans, 10 Hispanic Americans and 6 other. Preferred gambling modality electronic machines followed by cards, scratch/lottery, sports, animal races and craps or dice games.

N 357 screened by phone and 231 randomised Setting Outpatient clinic Intervention/indicator (A) n=84, Treatment: GA referral + individual CBT, Description: After the GA referral, participants met individually with a therapist 1 hr per week for 8 weeks.

Sessions were structured by handouts that addressed (a) discovering triggers, (b) functional analysis, (c) increasing pleasant activities, (d) self management planning, (e) coping with urges to gamble, (f) assertiveness training and gambling refusal skills, (g) changing irrational thinking, and (h) coping with lapses. A gambling-debt section was also provided, and most sessions had homework exercises. Ten masters-level and three doctoral-level therapists delivered the therapy. They received didactic training and close supervision of at least one case. Ongoing supervision consisted of regular review of therapy notes, audiotapes, and case discussion. (B) n=84, Treatment: GA referral + CB treatment in workbook format, Description: After GA referral, participants were given a 70-page workbook, containing CB exercises and a 24-page section on handling gambling-related debt (Petry, 1998). The workbook contained descriptions and fill-in-the-blank exercises identical to those in the therapy condition. The evaluator instructed participants to complete one chapter a week for 8 weeks.

Comparison/control (C) n=63, Treatment: GA referral only, Description: Participants were provided a list of the locations and meeting times of the 22 GA meetings held throughout the state of Connecticut, and GA was discussed, including prior attendance, expectations, and potential concerns. Participants were told that many people who become involved with GA reduce or stop gambling, and they were encouraged to select a GA meeting to attend. The GA alone and GA plus workbook were delivered in a one time 10-15 min session and participants did not meet again with a therapist.

Outcomes SOGS, Addiction Severity Index (ASI), TLFB: days gambled and amounts lost daily were recorded, Brief Symptom Inventory (BSI), Service Utilisation Form and collaterals identified by participants were interviewed independently about the participants' gambling behaviours.

Inclusion Criteria Met DSM-IV criteria for pathological gambling, had gambled in the past 2 months, were 18 years or older and could read at the 5th grade level Exclusion Criteria Current suicidal intentions, past month psychotic symptoms or already receiving gambling treatment.

Study Validity



No

This study was supported by a Grant from the National Institute of Mental Health.


Yes

The purpose of this study was to evaluate the efficacy of a short-term, CB treatment in a larger sample and compare its efficacy to a real-world control condition—referral to GA.


Yes


Yes


Yes


Yes Computerised urn randomisation balanced three groups on SOGS scores, age, gender, ethnicity and prior gambling treatment. Participants were randomised according to a 3:4:4 ratio for the three respective treatment conditions described below


Not reported


Not reported


Not reported


Not reported


Yes


Yes

Assessments were administered at baseline and 1, 2 (post-treatment), 6, and 12 months later.


Yes

Discusses psychometric properties of instruments used and collaterals were used to confirm self report data


Partial

Standardised tools were used. No mention of outcome assessor being blinded


Yes

Participants were randomised according to a 3:4:4 ratio for the three respective treatment conditions described below to account for the increased power required to determine differences between the two CB treatment conditions. Sample size was estimated at about 60, 80, and 80 for the three groups, calculated from effect sizes of other studies and adjusted for higher variability because of the use of an active control condition.


Partial

- The tests used were appropriate for the type of data (random effect regression) - Normality was addressed and where required variables were transformed - Reporting of some of the results was ambiguous - Point estimates and measures of variability were provided - An intention to treat sample was used in the analyses - There was no real comparison between the completers and the dropouts in this study


Partial

Baseline indices are shown in Table 1. Groups generally were similar, and only one variable evidenced significant differences across conditions. The GA referral condition had lower ASI Gambling scores at treatment initiation than the other groups, F(2,228) = 3.19, p< .05, so subsequent analyses of this variable took initial scores into account.


GA only 12 month dropout rate: 18/63=29%. GA+ workbook 12 month dropout rate: 18/84=21%. GA+CBT 12 month dropout rate:14/84=17%


Yes

Intention to treat


Yes


Yes


Yes

Other


Moderate



Results Time effects, indicating a reduction in gambling over time, were significant for all variables. The Time x CB contrast was significant for primary outcome measures, suggesting that improvement over time was greater in the CB than GA conditions. The Time x Mode contrast did not quite reach significance for ASI Gambling scores, but it was significant for SOGS scores. Table 2 also shows that participants in the CB conditions decreased days gambled to a greater extent over time than those in GA referral alone, whereas those assigned to individual CB therapy reduced dollar amounts gambled at a greater rate than those receiving the CB workbook. Author’s conclusions CB treatment reduced gambling relative to GA referral alone during the treatment period and resulted in clinically significant improvements, with some effects maintained throughout follow-up ( ps < .05). Individual CB therapy improved some outcomes compared with the CB workbook. Attendance at GA and number of CB therapy sessions or workbook exercises completed were associated with gambling abstinence. These data suggest the efficacy of this CB therapy approach.

Study ID (ie. Thomas 2009) and citation: Petry 2008. Petry NM, Weinstock J, Ledgerwood DM, Morasco B. A randomized trial of brief interventions for problem and pathological gamblers. Journal of consulting and clinical psychology. [Comparative Study. Randomized Controlled Trial. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't]. 2008 Apr;76(2):318-28.


Description of study: randomised controlled trial – level I evidence Patient/population Control group mean age=41.4(12.5), brief group mean age=43.5(14.4), MET group mean age=45.0(13.8) and MET+CBT group mean age= 44.0(10.2). Participants

recruited screening efforts, primarily at substance abuse treatment clinics/medical clinics, with flyers and advertisements. N=180, , 108 males, 72 females. 41 African Americans, 110 EuroAmericans,21 Hispanic Americans & 3 other. Preferred gambling mode of scratch/lottery followed by slot machines, cards, sports and dice.

N 2176 screened for eligibility, 436 invited for baseline evaluation and 180 randomised Setting Not repored Intervention/indicator (A) Motivational Enhancement Therapy (MET) +CBT, n=40, Participants assigned to this condition met with a research therapist after the baseline evaluation. They

received the same MET session as that described above and were encouraged to return for three sessions of CBT in the subsequent weeks. CBT sessions involved (a) determining internal and external triggers of gambling; (b) discussing methods for coping with internal gambling triggers, such as lonely, depressed, or anxious moods; and (c) developing methods for coping with external gambling triggers, such as assertiveness training, and for coping with gambling cues or cravings. We modified CBT session handouts from those in Petry (2005a) to emphasize reductions in gambling, rather than abstinence, as the goal. Nine therapists (two with bachelor’s degrees and seven with master’s degrees) delivered all three forms of therapy. They received didactic training and close supervision of at least one case. Ongoing supervision consisted of regular review of therapy notes and audiotapes and of case discussion. (B) MET, n=55, A 50-min MET session was held after the baseline evaluation. Therapists initially provided personalized feedback about participants’ gambling. Next, they explored positive and negative consequences of gambling and discussed how gambling fit within participant goals and values. Lastly, participants completed a change plan worksheet.

Comparison/control (C) brief advice, n=37, Participants assigned to this condition met with a research therapist immediately after the evaluation for about 10 min. Using a one-page handout, the research therapist described the participant’s own level of gambling in relation to that of the general population, outlined risk factors for development of severe gambling problems, and provided four steps with which to curtail development of significant gambling problems. (D)assessment only control, n=48, After the baseline evaluation had been completed, research assistants informed participants assigned to the assessment only control condition that they would be recontacted for follow-up evaluations in 6 weeks and 9 months.

Outcomes At baseline only NODS was used to assess lifetime pathological gambling with criteria from the DSM. The Addiction Severity Index evaluated problems at baseline and follow-up. The SOGS examined past-month gambling problems at baseline and through follow-up. The Brief Symptom Inventory was administered at baseline only. The primary outcome was ASI-G scores and dollars wagered in past 30 days secondary outcome.

Inclusion Criteria Individuals who endorsed at least 3 items on the SOGS, had spent at least $100 wagering and had gambled on at least four occasions in the past 2 months, and were 18 years or older were invited to participate in the full evaluation.

Exclusion Criteria Exclusion criteria were reading level below fifth grade, past month suicidal intentions or psychotic symptoms, or interest in receiving more intensive gambling treatment than that provided in the study.

Study Validity



No

Supported in part by the Patrick and Catherine Weldon Donaghue Medical Research Foundation and by National Institutes of Health Grants


Yes

In this study, we evaluated the efficacy of three brief interventions. We hypothesized that each condition would reduce gambling and related problems over the short term.


Yes


Yes


Yes


Not reported From envelopes, participants selected slips of paper that indicated the treatment group to which they were randomly assigned.


Yes From envelopes, participants selected slips of paper that indicated the treatment group to which they were randomly assigned.


No

Blinding participants to conditions was not possible


Not reported


Yes The condition to which participants were assigned was not stated on the follow up forms.


Yes


No

Assessment at baseline, week 6 and 9 months


Yes

The psychometric properties of instruments used were addressed and were adequate


Yes

Standardised tools were used and the outcome assessors were blinded


Partial

Sample size, at about 45 people per group was estimated from effect sizes of other gambling studies


Yes

- The tests used were appropriate for the type of data (random effects regression) - Normality was addressed and where required data was transformed - Missing data was minimal and handled appropriately - Point estimates and measures of variability were provided


Yes

Groups did not differ significantly on any demographic characteristic or on measures of gambling or of gambling problem severity at baseline.


6 week evaluation: control 1/48, brief advice 2/37, MET 3/55 and MET +CBT 2/40. 9 month evaluation: control 6/48, brief advice 6/37, MET 7/55 and MET+CBT 6/40

All participants assigned to brief advice received it. Some participants assigned to MET (n = 3, 5.5%) and some assigned to MET + CBT (n = 5, 12.5%) scheduled their session for another day and failed to attend. In the MET + CBT condition, 13 (32.5%) attended all four sessions, whereas 3 (7.5%) came to three sessions, 5 (12.5%) to two, and 14 (35.0%) to only one (the initial MET session).


Yes

Conservative intent-to-treat analyses were specified, as interventions may not be particularly useful if a minority of individuals receives them. Thus, all participants assigned to a condition were included in the analyses, regardless of their attendance.


Yes


Yes


Yes

Other


Low



Results Table 2 shows gambling variables over time. Time effects, which indicated general declines in gambling over time, were significant for ASI–G scores between baseline and Week 6 (see middle columns). The Group x Time interaction that compared the brief advice and control conditions was significant between baseline and Week 6. The brief advice condition evidenced significantly steeper slopes in reductions of ASI–G scores over time (see Figure 2). Similar effects were noted with dollars wagered over time (see Table 2 and Figure 3). The other conditions showed similar declines in gambling to that shown by the assessment only condition between baseline and Week 6. Table 2 also shows gambling indices between Week 6 and Month 9 (see right columns). The brief advice condition evidenced no further changes compared with the assessment only condition, but both groups continued gambling at lower levels than at baseline during this later assessment point (see Figures 2 and 3). Compared with assessment only participants, the MET + CBT participants had a steeper slope with respect to declines in ASI–G scores between Week 6 and Month 9, but Group x Time effects were not significant for dollars wagered. As we compared the MET and control conditions, no significant Group x Time interactions emerged, although the Group x Time interaction for ASI–G scores approached significance between Week 6 and Month 9. Author’s conclusions These results suggest the efficacy of a very brief intervention for reduction of gambling among problem and pathological gamblers who are not actively seeking gambling treatment.

Study ID (ie. Thomas 2009) and citation: Petry 2009.Petry NM, Weinstock J, Morasco BJ, Ledgerwood DM. Brief motivational interventions for college student problem gamblers. Addiction. 2009;104(9):1569-78.


Description of study: randomised controlled trial – level I evidence Patient/population 99 males and 18 females. Control mean age=20.5(2.0), brief advice mean age=20.2(1.9), MET mean age=20.5(1.4) and MET+CBT mean age=20.1(1.4). Preferred

gambling activity is cards/poker followed by sports, scratch/lottery and internet. N 1539 screened for eligibility, 128 invited for baseline evaluation and 117 randomised. Setting College campuses Intervention/indicator (a) MET+ CBT, n=21, These participants met with a therapist after the baseline evaluation for an MET session as above. They were encouraged to return for three

weekly individual sessions of CBT that addressed: (i) identifying internal (mood) and external (e.g. peer pressure) gambling triggers; (ii) coping with internal triggers; and (iii) coping with external triggers. CBT handouts were modified from Petry to emphasize reductions, rather than abstinence, as the goal. Six therapists (one bachelor’s level, two masters level, two clinical psychology doctoral students and one PhD psychologist) delivered each of the three interventions. They received didactic training and close supervision of at least one case. Ongoing supervision consisted of review of therapy notes and audiotapes and case discussion. (b) MET, n=30, Students in this condition received a 50-minute individual MET session after the evaluation. Therapists provided personalized feedback about the student’s gambling. Next, they explored positive and negative consequences of gambling and discussed how gambling fitted within their life goals and values. They then completed a change plan worksheet.

Comparison/control (c) Brief advice, n=32, Participants assigned to this condition met with a therapist immediately after the evaluation for 10–15 minutes. Using a one-page handout, modified from Petry, the therapist described the student’s level of gambling in relation to the general college population, outlined risk factors and provided four suggestions to curtail development of significant gambling problems. Suggestions included limiting amount of money spent gambling, reducing amount of time and days gambling, not viewing gambling as a way of making money and spending time doing other things. (d) Assessment only control, n=34, After the baseline evaluation, researchers informed students assigned to this condition that they would be re-contacted in 6 weeks and 9 months for follow-ups.

Outcomes SOGS at baseline, week 6 and 9 month. NODS at baseline only. TLFB at baseline only. Treatment service review. The primary outcome was ASI-G and days and dollars wagered in the prior month were secondary outcomes.

Inclusion Criteria Students who were 18 years or older, responded affirmatively to 3 or more SOGS items, spent $100 or more in total wagering and gambled on 4 or more days in the past 2 months were invited to participate in the full evaluation. Gambling frequency/intensity criteria were included to ensure that study participants had levels of gambling that could decrease during the study period, and prior research revealed that these levels of gambling were associated with problem gambling.

Exclusion Criteria Exclusion criteria were past-month suicidal intentions, psychotic symptoms or interest in receiving more intensive gambling treatment than provided in the study, as an assessment-only condition was utilized.

Study Validity



No

This research was funded by NIH grants.


Yes

In this study, we evaluated each of these three interventions in problem and pathological gambling college students.


Yes


Yes


Yes


Not reported Participants selected from envelopes containing slips of paper indicating the group to which they were assigned randomly.


Yes Participants selected from envelopes containing slips of paper indicating the group to which they were assigned randomly.


Not reported


Not reported


Yes Seven research assistants (some of whom also were therapists) shared responsibilities for follow-ups and were unaware of treatment assignment.


Yes


No

Assessment at baseline, week 6 and 9 months


Yes

Psychometric properties of measures addressed and were adequate.


Yes

Standardised measures used. Outcome assessors were blinded.


Yes

117 students were randomised. This sample size is sufficient to detect, with >80% power, medium effect sizes between the assessment-only condition and the combined group of participants receiving any intervention. A sample size of 25–30 per condition is also adequate to detect medium to large effect sizes between each intervention and the assessment-only condition.


Yes - The tests used were appropriate for the type of data (hierarchical linear modelling) - Normality was addressed and where required variables were transformed - The dropout rate was very low and the missing data was handled appropriately - Point estimates and measures of variability were provided


Yes

Groups did not differ significantly on any demographic variables or measures of gambling.


Control: 6 week: 0%, 9 month:1/34=3%.

Brief Advice: 6 week:0%, 9 month:0%.

MET:6 week:0%, 9 month:1/30=3%.

MET+CBT: 6 week:3/21=14%, 9 month:2/21=10%


Yes Intention to treat analysis was used.


Yes


Yes


Yes

Other


Low



Results

Table 2 shows gambling variables over time in the three conditions. For ASI-G scores, the group x time interaction effect was significant for the contrast of any treatment versus no treatment, t(115) = 2.28, P < 0.05, and for each of the three interventions compared to the assessment-only condition (Table 2). Figure 2 shows that although ASI-G scores remained generally unchanged over time in the assessment-only condition, they decreased in all three of the active interventions. There were no significant differences between active interventions with respect to changes in ASI-G scores over time (all Ps > 0.35). Table 2 also shows two supplementary indices of gambling. In terms of days gambled, time effects were significant over the 9-month study period, showing a general decline in days gambling (Fig. 3). The omnibus analysis comparing any intervention to the assessment only condition revealed a significant treatment x time effect, t(115) = 2.24, P < 0.04, but none of the three interventions differed significantly from the assessment-only condition in terms of days gambled. With respect to dollars wagered, again the omnibus analysis comparing any treatment to no treatment found a significant treatment x time effect, t(115) = 2.22, P < 0.05. Only the MET condition showed a significantly greater reduction in dollars wagered over time compared to the control condition (Table 2; Fig. 4). None of the active interventions differed significantly from one another with respect to days or dollars gambled over time (all Ps > 0.28). Author’s conclusions Results from this study show that identifying problem gamblers and administering very brief intervention strategies such as one MET session can assist in substantially decreasing gambling for 9months in almost two-thirds of college student problem and pathological gamblers. Given the lack of efficacious interventions for this population, these results are noteworthy. As awareness of gambling problems on college campuses grows, more counsellors, administrators and professors are expressing interest in learning about this disorder, and these data provide support for brief interventions in this population.

Study ID (ie. Thomas 2009) and citation: Saiz-Ruiz 2005. Saiz-Ruiz J, Blanco C, Ibanez A, Masramon X, Gomez MM, Madrigal M, et al. Sertraline treatment of pathological gambling: a pilot study. The Journal of clinical psychiatry. [Clinical Trial. Comparative Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 2005 Jan;66(1):28-33.

Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: Spain

Description of study: randomised controlled trial – level I evidence Patient/population 6 females and 60 males, Mean age=38.9 (11.6). N 66 randomised, 6 withdrew and 60 were included in analyses Setting Outpatient Intervention/indicator n=33. Treatment: sertraline. Duration: 24 weeks. Dose: Following randomisation, treatment was initiated at 50mg/day of sertraline or matched placebo equivalent

during week 1. Sertraline could be increased to 100mg/day at the end of week 4 and up to 150mg/day from the end of week 8 until the end of the study, based on clinical response and tolerability. Reductions in the dosage of study medication to the next previous level were allowed if a patient was experiencing a side effect; once the side effect subsided, the dosage could be titrated back up. Subjects who missed 30 days or more of medication were discontinued from the study. Mean dose was 95mg/day.

Comparison/control n=33. Treatment: placebo. Duration: 24 weeks. Dose: Following randomisation, treatment was initiated at 50mg/day of sertraline or matched placebo equivalent during week 1. Mean dose was 100mg/day

Outcomes Criteria for Control of Pathological Gambling Questionnaire (CCPGQ), PG-CGI-I, Visual Analogue Scales (VAS), SOGS and Eysenck Impulsiveness Questionnaire (EIQ).

Inclusion Criteria Meeting DSM-IV criteria for pathological gambling Exclusion Criteria (1) Current co-morbid major depressive disorder (2) current or lifetime history of bipolar disorder, schizophrenia or other psychotic disorder (3) alcohol or

substance dependence or abuse in the past 3 months. Concomitant psychotropic medication was not allowed during the study and all previous ineffective psychotropic medications were discontinued before study start. Patients undergoing individual or group psychotherapy or participating in GA were excluded. Individuals with an unstable coexisting medical condition were not eligible for the study. Women's participation was contingent upon negative results of a beta-human chorionic gonadotropin pregnancy test and stable use of medically accepted form of contraception.

Study Validity



Yes

Financial support from Pfizer Spain. Dr Saiz-Ruiz has received grant/research support from Eli Lilly and has participated in speakers' or advisory boards for Bristol Myers Squibb. Dr Blanco has received grant/research support from GlaxoSmitheKline and BioTie. Dr Ibanez has received grant/research support from Pfizer.


Yes

The goal of this study was to examine the tolerability and efficacy of sertraline in the treatment of pathological gambling.


Yes


Yes


Yes


Not reported


Not reported


Yes

Double blind


Yes

Double blind


Not reported


Yes


No

No follow up


Yes

The psychometric properties were addressed and adequate


Partial

Standardised tests used. No mention of blinding outcome assessors


No

The power of the study was limited by the high placebo response rate and the small sample size.


Partial

- Chi-square tests, t-tests, mixed effects model and ANCOVA were appropriate for the type of data. - Did not test for normality. - Even though there were no significant differences between the groups at baseline they used baseline as a covariate as well as demographics. - Used an intention to treat sample and provided no comparison of the dropouts with the completers.


Yes

Show in table


Placebo:4/33=12% and Treatment:2/33=6% and weren't included in analyses

Of 66 randomised patients 53 completed at least a month, 49 completed 2 months, 44 completed 3 months, 42 completed 4 months, 40 completed 5 months and 37 completed the full pilot study


Yes

The intention to treat population comprised all patients randomly assigned to double blind study medication who had a baseline assessment and had taken at least 1 dose of medication.


Yes


Yes


Yes

Other


Moderate



Results Treatment with sertraline did not yield significantly greater efficacy than placebo at any point during the study as assessed by the CCPGQ. By week 2, 26 patients (84%) in the sertraline group and 20 patients (69%) in the placebo group were responders. At the last visit 23 sertraline treated subjects (74%) and 21 placebo treated subjects (72%) were classified as responders. Response rates using the PG-CGI-I scale followed a slightly different pattern but also failed to find differences between sertraline and placebo. There were no significant differences between the groups in VAS scores for frequency of gambling, amount of money gambled, severity of gambling or improvement using LOCF analysis or mixed random regression models. Similarly, there were no differences between the groups in score changes on the overall EIQ or any of its subscales. Author’s conclusions Sertraline was not statistically significantly superior to placebo in the overall sample. The power of the study was limited by the high placebo response rate and the small sample size

Study ID (ie. Thomas 2009) and citation: Sani 2005. Sani A, Carlevaro, T, Ladouceur, R. Impact of a counselling session on at-risk casino patrons: A pilot study. Gambling Research. 2005;17(1):47-52.

Initials of person extracting/appraising data: SM Type of publication: Peer reviewed journal article Language of publication: English Country the study was conducted: Switzerland

Description of study: randomised controlled trial – level I evidence Patient/population Participants were casino patrons, 7 males and 5 females, 42% are Swiss Citizens and 33% Italians. Mean age is 50 years N N=12 Setting Casino Locarno in Switzerland Intervention/indicator n=6. Treatment: counselling session. The counselling session is used as a preventive measure in order to increase the gamblers' awareness of their gambling

behaviour. It involves the following components: (1) collecting socio demographic data (2) identifying gambling habits (3) evaluating the presence of pathological gambling according to DSM-IV criteria (4) providing information regarding what pathological gambling is and the negative consequences

Comparison/control n=6. Treatment: control group. Participants of this group did not receive the counselling session, nor feedback on their gambling habits. Outcomes Time spent gambling, number of visits, total money gambled and total money lost determined by the supervisor monitoring the gambling behaviour though

closed circuit TV Inclusion Criteria Score of 5 or more on the DSM-IV criteria for pathological gamblers. Exclusion Criteria Not reported

Study Validity



Not reported


Yes

The present research evaluates the impact of a counselling session for at risk casinos patrons, before an exclusion procedure is implemented.


Yes


Partial



Yes

The criteria mentioned were appropriate


Not reported


Not reported


Not reported


Not reported


Not reported


Yes


No

No follow up


Yes

Outcomes were measures by the supervisor monitoring the gambling behaviour though closed circuit TV


Yes


No

Sample size so small that it did not permit statistical analyses


N/A

Sample size so small that it did not permit statistical analyses.


Not reported


Not reported


Not reported


Yes


Yes


Yes

Other



Results Results show that the counselling session reduced the monthly average time spent gambling, number of visits to the casino, amount of money gambled and the money lost. Although these differences were not statistically significant between groups, the trend is in the expected direction. Author’s conclusions Results suggest that providing feedback produced positive outcomes on all dependent variables. This study provides some indications about interesting avenues to pursue in order to increase the efficacy of self-exclusion programs. Some limitations must be pointed out. First, since it was designed as a preliminary study, the sample size is small and does not permit statistical analyses. Secondly, 6 and 12 month follow-ups must be conducted in order to assess the maintenance of this new gambling pattern. Finally, future research should aim to identify the characteristics of the gamblers who are most likely to benefit from such a procedure.

Study ID (ie. Thomas 2009) and citation: Sylvain 1997. Sylvain C, Ladouceur R, Boisvert JM. Cognitive and behavioral treatment of pathological gambling: a controlled study. Journal of consulting and clinical psychology. [Clinical Trial. Randomized Controlled Trial. Research Support, Non-U.S. Gov't]. 1997 Oct;65(5):727-32. Ladouceur R, Sylvain C. Treatment of pathological gambling: A controlled study. Anuario de Psicologia. 1999 Dec;30(4):127-35.


Description of study: randomised controlled trial – level I evidence Patient/population Community or referral sample. All males. Treatment group mean age=37.6(10.3) and control group mean age=42.6(12.1) N 58 recruited and 40 randomised. 11 dropped out so the final sample was 29. Setting Not reported Intervention/indicator n=14. Treatment: CBT. Treatment was administered on an individual basis with one or two weekly sessions lasting 60 to 90 min each depending of the goals

expressed by the patient. Participants in the treatment group received an average of 16.7 hr of treatment (SD = 5.7), with a maximum of 30 hr of treatment. Treatment was conducted until patients developed an adequate perception of gambling and chance and ceased gambling. Participants did not receive any other treatment while they were in the study. The treatment included four components: cognitive correction, problem solving training, social skills training and relapse prevention. All sessions were recorded, and therapists completed a checklist of interventions at the end of each session. An independent evaluator then listened to 20% of the interviews for each participant to ensure that the treatment was administered as indicated on the checklists. Components identified by the therapist were always Confirmed by a second evaluator (100%). All sessions that were rated by the evaluator had at least one component of the treatment identified. More specifically, 48% of the sessions contained information about gambling and the cognitive correction of relevant beliefs. Finally, the development of skills pertaining to problem solving and relapse prevention were noted in 28% and 56% of the sessions, respectively.

Comparison/control n=15. Treatment: wait list control. At intake, all participants were informed that, because of random assignment to immediate or delayed treatment, there was a possibility that they would not receive treatment immediately. After evaluation, participants in the control group were contacted and told that their name would be placed on a waiting list. The therapist assured the participants that they would be called as soon as a place became available. It was expected that all participants would be offered treatment in the following 4 months. In the meantime, the therapist contacted them by telephone once a month. Two patients could not wait longer and were immediately assigned to the treatment group. None of these patients sought alternate treatment while on the waiting list.

Outcomes The dependent variables were as follows: number of DSM-III-R criteria met, the SOGS, perception of control, desire to gamble, self-efficacy perception, and frequency of gambling. The number of DSM-III-R criteria for pathological gambling was assessed by clinical interview (score range, 0-9).

Inclusion Criteria All gamblers were identified as meeting criteria of the DSM-III-R for pathological gambling Exclusion Criteria

Study Validity



No

This research was supported by grants from the Conseil Quebecois de la Recherche Sociale and from Loto-Quebec.


Yes

The present article evaluates the efficacy of a treatment package that corrects this dysfunctional schema and uses problem-solving techniques and social skills training when necessary.


Yes


Partial



Yes


Not reported Participants were randomly assigned to treatment or wait-list control groups.


Not reported


Not reported


Not reported


Not reported


Yes


Yes

They completed dependent measures at pre-test, post-test, post wait-list, and 6-month follow-up. A 12-month follow-up was also conducted.


Partial

The SOGS is a validated and reliable tool. The psychometric properties of the other scales used were not mentioned


Partial

Some standardised tools were used. No mention of blinding outcome assessors


Not reported

Found significant differences between groups


Partial - The tests were appropriate for the type of data, however, the sample size was very small (MANOVA) - Normality was assessed and nonparametric tests were used where required - Point estimates and measures of variability were provided - There was no intention to treat analysis. Only completers were included in the analyses


Yes

A multivariate analysis of variance (MANOVA) revealed no significant differences between the treatment and control groups on the first five dependent variables. Frequency-of-gambling scores were not distributed normally and revealed a large Variability. Therefore, they were analysed separately with nonparametric analyses of variance. There were no significant differences for number of gambling sessions, number of hours spent gambling, or amount of money bet for the week.


11/40. 8 from treatment and 3 from control

40 randomised. 11 dropped out so the final sample was 29.


No

40 randomised. 11 dropped out so the final sample was 29.


Partial

Didn't report results on 12 month follow up


Yes


Yes

Other



Results Tests of simple effects showed that the treatment and control group means differed significantly at post-test for all five variables: participants in the treatment group met fewer diagnostic criteria, reported less desire to gamble and had a lower SOGS score. They also reported a significantly higher perception of control and self-efficacy. Author’s conclusions In conclusion, this controlled study shows the effectiveness of a cognitive and behavioural treatment for pathological gamblers. Furthermore, results proved to be both statistically and clinically significant.

Study ID (ie. Thomas 2009) and citation: Toneatto 2009. Toneatto T, Brands B, Selby P, Toneatto T, Brands B, Selby P. A randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of concurrent alcohol use disorder and pathological gambling. Am J Addict. [Randomized Controlled Trial Research Support, Non-U.S. Gov't]. 2009 May-Jun;18(3):219-25.


Description of study: randomised controlled trial – level I evidence Patient/population Community sample. The sample was primarily male (93%), approximately 40 years old, generally under-employed (52%), not partnered (76%), and high-school

educated (45%). N 326 screened, 135 eligible, 74 completed initial assessment and 52 were randomised Setting Centre for Addiction and Mental Health Intervention/indicator n=27. Treatment: naltrexone and CBT. Week 1 placebo run in phase: The first week of the study was designated as a single-blind placebo run-in phase. All eligible

subjects were asked to take a daily placebo capsule, identical in appearance to the naltrexone capsules that were administered during the double-blind phase. Placebo responders (n = 1), individuals who decreased their gambling behaviour and alcohol consumption by 50% or more, were excluded from the study. Weeks 2-12 Pharmacotherapy: The initial dose of naltrexone was set at 25 mg/day for three days and 50 mg/day for the following 11 days. At the end of this period, the dose remained constant at 50 mg/day or increased by increments of 50 mg. The criterion for increasing the dose was based on patient self-report of lack of therapeutic effect on alcohol consumption and the physician’s clinical judgment. Dose increases could occur every two weeks until a maximum of 250 mg was reached. ALSO psychological intervention weeks 2-12: Subjects received up to seven sessions of cognitive behavioural treatment for both the gambling and alcohol problems on weeks 2, 3, 4, 6, 8, 10, and 12. Therapeutic interventions were consistent with brief, practical, problem-solving approaches shown to be effective in the treatment of problem gambling. Mean dose was 100mg (59.4). Counselling was administered by three experienced (two doctoral and one masters level) addiction therapists and supervised by the PI using treatment guidelines developed specifically for this study.

Comparison/control n=25. Treatment: placebo and CBT. Week 1 placebo run in phase: The first week of the study was designated as a single-blind placebo run-in phase. All eligible subjects were asked to take a daily placebo capsule, identical in appearance to the naltrexone capsules that were administered during the double-blind phase. Placebo responders (n = 1), individuals who decreased their gambling behaviour and alcohol consumption by 50% or more, were excluded from the study. Weeks 2-12 Placebo: Identical appearing placebo capsule. ALSO psychological intervention weeks 2-12: Subjects received up to seven sessions of cognitive behavioural treatment for both the gambling and alcohol problems on weeks 2, 3, 4, 6, 8, 10, and 12. Therapeutic interventions were consistent with brief, practical, problem-solving approaches shown to be effective in the treatment of problem gambling. Mean dose 97.5mg (41.3).

Outcomes Subjects self-monitored alcohol quantity and frequency, gambling episodes and expenditures on a daily basis using a calendar specially designed for the study. Inclusion Criteria The primary inclusion criterion was meeting the diagnostic criteria for an alcohol use disorder (ie, abuse, dependence) and pathological gambling. Exclusion Criteria Exclusion criteria included dependence or abuse of any other psychoactive substances (except nicotine), serious medical illness, laboratory evidence of significant

hepatocellular injury, use of disulfiram, use of opioid-containing medications, psychosocial crisis, pregnancy, and inability to read or write English. Study Validity



No

This research was supported by a grant from the Ontario Problem Gambling Research Centre.


Yes

There have been no published controlled clinical trials of naltrexone for concurrent alcohol dependence and pathological gambling apart from the encouraging preliminary results of a case study. Based on the substantial evidence for the clinical efficacy of naltrexone and nalmefene with alcohol dependence and the growing evidence for its efficacy in problem gambling there is conceptual and empirical justification for conducting a randomised control trial of naltrexone as a pharmacotherapy for concurrent alcohol abuse/dependence and pathological gambling.


Yes


Yes


Yes


Not reported At the end of the placebo run-in phase, all placebo non-responders were randomised to receive either naltrexone or the identical-appearing placebo capsule.


Not reported


Yes

Double blind study


Yes

The research coordinator, nurse, physician, principal investigators and therapists were blind to group assignment.


Not reported


Yes


Yes

3,6 and 12 month follow up


Partial

Some measures used are valid and reliable however they used self report data without validation from third party


Partial

Some standardised tools were used. Not aware if outcome assessors were blinded


Not reported


Yes

- Repeated measures ANOVA was appropriate for the type of data - Normality was checked - Mean and standard deviations were provided - Missing data was handled appropriately with ITT and completers analyses - There were no confounding variables


Yes

A comparison of demographic variables revealed no group differences. Table 2 describes baseline patterns of alcohol use and gambling. No group differences were found.


All 25 participants completed treatment for placebo, 21/25 completed at 3 months, 18/25 at 6 months and 19/25 at 12 months. 26/27 completed naltrexone treatment, 17/27 at 3 months and 6 months and 19/27 at 12 months.


Yes

An intent-to-treat analysis approach was adopted using the LOCF approach. However, analysis of completers only was also conducted.


Yes


Yes


Yes

Other


Moderate



Results No Group effect was found for either gambling variable. Significant Time effects were found for gambling-related expenditures per day, F = 3.02, df = 2, 100, p < .04, and gambling-frequency, F = 8.71, df = 2, 100, p < .001; < .001. No Time X Group interactions were significant. The results of the repeated measures ANOVA are summarized in Table 4. Contrasts revealed that the frequency of gambling was significantly lower at the end-of-treatment compared to baseline, F = 13.44, df = 1, 50, p < .001 but not between end-of-treatment and the one-year follow-up, F = 0.09, df = 1, 50, ns. Similarly, contrasts revealed that gambling-related expenditures were significantly lower at the end-of-treatment compared to baseline, F = 14.15, df = 1, 50, p < .001 but not between end-of-treatment and the one-year follow-up, F = 1.68, df = 1, 50, ns. Inspection of the means in Table 3 shows that the gains achieved at the end-of-treatment were generally retained throughout the follow-up period. The sample reduced their gambling frequency by approximately six days per month (37% between baseline and 12-month follow-up for both groups). A 50% reduction in gambling expenditures was found between baseline and 12-month follow-up for both groups. The results of the completer analyses yielded identical findings to the intention-to-treat analysis and are also summarized in Table 4. The effect size for the analyses for both the frequency and expenditures related to gambling were in the moderate range when baseline and end-of-treatment were compared but small or negligible during the one-year post-treatment period. Author’s conclusions No significant group differences were found on any alcohol or gambling variable (ie, frequency, quantity, expenditures) at post-treatment or at the one year follow-up. However, a strong time effect was found suggesting that treatment, in general, was effective. The use of naltrexone to treat concurrent alcohol use and gambling problems was not supported.

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