Measuring Outcome in the Treatment of Cocaine Dependence

Paul Crits-Christoph, Ph.D.Mary Beth Connolly Gibbons, Ph.D.

Robert Gallop, Ph.D.Jaclyn S. Sadicario, B.A.

George Woody, M.D.

Department of PsychiatryUniversity of Pennsylvania

Primary Goal of NIDA Cocaine Collaborative Study

In the treatment of cocaine dependence,

to compare the efficacy of:

Group Drug Counseling Along (GDC) Cognitive Therapy (CT) plus GDC Supportive-Expressive (SE) Therapy plus GDC Individual Drug Counseling (IDC) Plus GDC

Background

New research (McCann & Li, 2012) has demonstrated that number of weeks abstinent during and after treatment can reveal significant differences in outcome between treatments, even when previous analyses found no differences.

Goal of Current Study To evaluate the merits of different methods for

measuring outcomes including: – End-of-study abstinence measures during the active

treatment of cocaine dependence. Thus, we explored the associations between

active treatment phase cocaine use outcomes and (1) measures of cocaine use across follow-up, and (2) broader measures of functioning during active treatment and follow- up.

Design of Study 6 months of treatment Maximum of 24 group sessions;

36 individual sessions Experienced and trained counselors/therapists N=487 patients randomized Assessments of drug use and functioning obtained

at baseline and monthly for 6 months Addiction Severity Index (ASI) used to measure

functioning in addiction-related domains. Urines and self-report of cocaine use obtained

weekly

Patient Sample

Average age = 34 years, range 19-59 77% males, 23% females 58% Caucasian 42% minority (primarily African American) 60% employed 70% live alone 81% crack users, 19% intra-nasal users 33% current alcohol dependence 29% cocaine-induced mood disorder

Attrition

15 of 36 individual sessions completed

10 of 24 group sessions attended

Despite this attrition from treatment: - 94% completed at least one post-randomization assessment - 83% completed a 9 or 12 month follow-up

Mean ASI Drug Use Composite

0.08

0.10

0.12

0.14

0.16

0.18

0.20

0.22

0.24

Intake 1 2 3 4 5 6

IDCCTSEGDC

Month

IDC significantly better than CT, SE, and GDC, P’s < 0.01

Percent of Patients Achieving Three Months Abstinence

36

22

17

25

0

5

10

15

20

25

30

35

40

IDC CT SE GDC

Question: How best to measure outcomein the treatment of cocaine dependence?

1. What measures of during-treatment cocaine use best predict end-of-treatment functional outcomes?

2. What measures of during-treatment cocaine use best predict drug use outcomes at follow-up?

3. What measures of during-treatment cocaine use best predict functional outcomes at follow-up?

  ASI Scales at 12 Months

Within-Treatment Outcome Psych Family/Social Medical Legal Employment

Average times used cocaine past week .13* .09 -.05 .15** .14*

Max. consecutive days abstinent from cocaine from self-report

-.00 -.11 .04 -.10 -.05

Completely abstinent (urine + self-report) -.02 -.10 .07 -.08 -.03

4+ weeks of abstinence (urine + self-report) .02 -.05 -.05 -.14* .09

3+ weeks of abstinence (urine + self-report) -.03 -.03 -.09 -.16** -.10

2+ weeks of abstinence (urine + self-report) .02 -.06 .10 -.17** -.03

1+ weeks of abstinence (urine + self-report) -.02 -.07 -.04 -.15** -.05

Percent reduction in cocaine use from baseline to month 6 (self-report)

-.13* -.07 -.01 -.14* -.14*

50% reduction from baseline (yes/no) -.16** -.10 .00 -.17** -.06

% (of available) Negative Urines for cocaine -.04 -.06 -.01 -.12* .07

% (scheduled) Negative Urines for cocaine -.02 -.09 .04 -.15* -.03

Note. Partial correlations shown with treatment group, site, and baseline ASI scores as covariate. N’s vary from 337 to 363.

Within-treatment cocaine outcomes (months 1 to 6) predicting 12 month (after baseline) follow-up functioning

  Drug Use Outcomes at 12 Months Within-Treatment Outcome

Mean (SD)or percent

Days Using Cocaine

Past Month

Abstinent past month

Abstinent past 3 months

ASI Drug Use

Average times used cocaine past week 0.75 (1.10) .27 -.27 -.25 .24

Max. consecutive days abstinent from cocaine from self-report

60.7 (63.7) -.22 .32 .40 -.27

Completely abstinent (urine + self-report) 11.8% -.18 .31 .38 -.21

4+ weeks of abstinence (urine + self-report) 51.3% -.15** .12* .15** -.14*

3+ weeks of abstinence (urine + self-report)58.8% -.17** .12* .15** -.14*

2+ weeks of abstinence (urine + self-report) 70.6% -.20 .16** .15** -.16**

1+ weeks of abstinence (urine + self-report) 81.9% -.14* .13* .13* -.15**

Percent reduction in cocaine use from baseline to month 6 (self-report)

67.7 (56.6) -.23 .26 .31 -.27

50% reduction from baseline (yes/no) 78.1% -.23 .25 .29 -.29***

% (of available) Negative Urines for cocaine0.67 (0.41) -.18** .25 .28*** -.23***

% (scheduled) Negative Urines for cocaine0.49 (0.32) -.20 .26 .28*** -.22***

Within-treatment cocaine outcomes (months 1 to 6) predicting 12 month (after baseline) drug use outcomes.

Note. Partial correlations shown with treatment group and site used as covariates. Baseline scores for ASI Drug Use Composite and Days Used Past Month also used as covariates for those outcomes. Sample sizes vary from 337 to 363 due to missing data.* p< .05. ** p< .01. p<.001.

McCann, DJ., & Li SH (2012). A Novel, Nonbinary Evaluation of Success and Failure Reveals Bupropion Efficacy Versus Methamphetamine Dependence: Reanalysis of a Multisite Trial. CNS Neuroscience & Therapeutics, 18, 414–418.

EOSA = end of study abstinence. e.g., 2+ weeks abstinent immediately prior to end of treatment

NOBWOS = number of beyond-threshold weeks of success. e.g., if threshold is 2 weeks abstinent prior to treatment end, patient has to achieve 3 or more weeks abstinent

We added:

Number of consecutive weeks of abstinence from the end of the study

Does Looking at Abstinence at the End of Treatment Help?

Drug Use Measures at 12 Months (after baseline)

 McCann and LiWithin-Treatment Outcomes

 Mean Mean(SD) or percent

 Days Using Cocaine in Past Month

 Abstinent during Past month

 Abstinent during Past 3 months

 ASI Drug UseComposite at 9

months

EOSA – 1+ wks 45.1% (n=152) -.04 .18** .17** .20***EOSA -2+ wks

24.3% (n=82) -.15** .22*** .25*** -.26***

EOSA -3+ wks 15.7% (n=53) -.12* .22*** .24*** -.18**EOSA – 4+ wks 12.2% (n=41) -.16** .22*** .26*** -.20***NOBWOS – 1+ wks 1.25 (3.81) -.15** .22*** .26*** -.20***NOBWOS – 2+ wks 1.00 (3.58) -.14* .21*** .24*** -.18***NOBWOS – 3+ wks 0.85 (3.35) .13* .20*** .23*** -.18**NOBWOS – 4+ wks

0.72 (3.14) -.13* .19*** .22*** -.17**

Number of consec. wks abstinent from endpoint

 1.70 (4.01)

 -.14**

 .23***

 .26***

 -.22***

McCann and Li Within-treatment cocaine outcomes (months 1 to 6) predicting 12 month (after baseline) drug use measures

Note. EOSA = end of study abstinence. NOBWOS=number of beyond-threshold weeks of success.Partial correlations shown with treatment group and site used as covariates. Baseline scores for ASI Drug Use Composite and Days Used Past Month also used as covariates for those outcomes. N=337.p< .05. ** p< .01. p <.001.

EOSA=end of study abstinence.NOBWOS=number of beyond-threshold weeks of success. Lower ASI scores=fewer problems. * p < .05. ** p< .01

ASI Scales at 12 Months

Within-Treatment Outcome Psych Family/Social Medical Legal Employment

EOSA – 1+ wks -.00 -.04 .09 .02 .07

EOSA -2+ wks -.03 -.12 .08 -.05 -.01

EOSA -3+ wks -.07 -.08 .02 -.04 -.12*

EOSA – 4+ wks -.13* -.06 .01 -.01 -.09

NOBWOS – 1+ wks -.06 -.07 .03 -.02 -.08

NOBWOS – 2+ wks -.06 -.06 .02 -.01 -.08

NOBWOS – 3+ wks -.05 -.05 .02 -.01 -.07

NOBWOS – 4+ wks -.04 -.05 .03 -.01 -.07

Number of consec. wks abstinent from endpoint

-.05 -.07 .04 -.01 -.06

Within-treatment cocaine outcomes (months 1 to 6) predicting 12 month (after baseline) follow-up functioning.

Conclusions

■ Within-study cocaine use measures moderately associated with cocaine/drug use at 12 months.

- Abstinence based measures look best, urine samples showed no correlation except for legal problems

■ Within-study cocaine use measures not associated with functioning at treatment endpoint or at 1-year follow-up.

■ End of study abstinence weeks, and weeks beyond threshold

associated with cocaine use/abstinence measures at 1-year follow-up, but not functioning

- Count of weeks abstinence at end of treatment works as well

Conclusions

■ Drug use is episodic. Very few “intermittent users”, mostly continuous users and abstainers.

■ Some people function relatively well despite drug use.■ Unable to summarize outcome in one success/fail index.

Limitations■ Distributions of outcome measures■ Use of correlations to compare (but odds ratio better)■ Complete abstainers result in restrictive range of predictors■ Sample: patients with psychiatric comorbidities requiring

any psychotropic medications (including antidepressants) were excluded

■ Other functioning measures (outside of ASI) not included

18

Amphetamine Addiction in Iceland and Extended Release Injectable Ntx

Valgerður Rúnarsdóttir, M.D.,

Vogur Hospital Iceland

SAA National Center of Addiction Medicine

Ingunn Hansdóttir, PhD,

Assistant Professor University of Iceland

Research Counsil Member SAA National Center of Addiction Medicine

Symposium on Emerging Data on Efficacy and Clinical Applications of Extended Release Naltrexone Formulations,

presented at 75th Annual Meeting - College on Problems of Drug Dependence - June 15-20, 2013, San Diego, CA

19

Swedish studies

Jayaram-Lindstrom et al Am.J. Psychiatry, 2008 Significant effect using oral naltrexone in

ramdomized, placebo-controlled 12 week trial of 80 amphetmine dependent outpatients.

20

21

Icelandic setting

Centralized addiction treatment Good access to treatment Vogur hospital lynchpin in addiction trmt Population endorses disease concept Well trained staff Evidence based practice

22

Icelandic setting - Treatment as usual: Detox Hospitalization 7-10 days

Residential: 4 weeks

Intensive outpatient 5x week for 1 mo (60 hrs) 1x week for 3 mo (12 hrs)

Outpatient follow-up 2x week for 3 mo (24 hrs) 1x week for 9 mo (36 hrs)

Detox

7-10 days

Residential4 weeks

Outpatient intensive

Outpatient follow-up

23

Study Design -I

100 amphetamine dependent treatment seeking patients at Vogur Hospital

Randomized, double blind trial og 6 month trmt with VIVITROL® or VIVITROL®placebo and Treatment as usual

Stratified by gender and IV status. All participants detoxed at Vogur Hospital and

consented. Randomized before going to outpatient status.

24

Baseline diagnoses

DSM-IV checklist physician diagnosis

N (%)

Amphetamine dependence 100Alcohol dependence 75Cannabis dependence 69Cocaine dependence 26Methylphenidate dependence 15Sedative dependence 30Opiate dependence 0

25

RetentionNumber of subjects receiving study treatment

injection 1 injection 2 injection 3 injection 4 injection 5 injection 60

10

20

30

40

50

60

70

80

90

100100

72

56

47 46

37

TotalTreatmentPlacebo

Negative urines;%1247 urines collected (1194-/53+) 2400 urines target

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Observed Treatment

Observed Placebo

Imputed Treatment

Imputed Placebo

27

% Drug Negative Urines(N=1257)

Amphetamine:: 4.25 Benzodiazepines: 8.26 Marijuana: 6.98 Cocaine: 1.44 Opioids: 0.96

28

Conclusions

Robust response to treatment as usual for those who stayed in trmt with no additional benefit from Naltrexone.

Different sample & more psychosocial rx than Swedish srudy

Trend towards worse outcome for those going directly to outpatient

Have not analyzed data as per McCann & Li