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Subjective wellbeing under quetiapine treatment: Effect of diagnosis, moodstate, and anxiety
Martin Lambert a, Dieter Naber a, Anne Karowa, Christian G. Huber a, Jürgen Köhler b,Joachim Heymann b, Benno G. Schimmelmann c,⁎a Psychosis Early Detection and Intervention Centre (PEDIC), Centre for Psychosocial Medicine, Department of Psychiatry and Psychotherapy,University Medical Center Hamburg-Eppendorf, Germanyb AstraZeneca GmbH, Medical Neuroscience Department, Wedel, Germanyc Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Virchowstr. 174, 45147 Essen, Germany
Article history:Received 31 March 2008Received in revised form 22 February 2009Accepted 3 March 2009Available online 24 March 2009
Objective: To examine the effect of diagnosis, mood state, and anxiety on subjective wellbeingin patients with affective and non-affective psychotic disorders treated with quetiapine IR.Methods: 2175 patients with schizophrenia-spectrum (SZ, n=1681), schizoaffective (SA,n=249), and bipolar disorder (BPD, n=245) were treated with quetiapine over 6 months andassessed with the Clinical Global Impression-Severity of illness Scale (CGI-S) and the SubjectiveWellbeing under Neuroleptic Treatment Scale (SWN-K). Diagnostic group differences andeffects of mood state and anxiety on subjective wellbeing were analyzed using multi-factoriallinear regression analysis and mixed models repeated measures.Results: At baseline, despite similar CGI-S scores, significant SWN-K score differences betweenSZ (57.7 points), SA (64.1 points), and BPD (79.5 points) were detected. At baseline, depression(pb0.001) and anxiety (pb0.001) were independently associated with a worse and mania(pb0.001) with a better subjectivewellbeing. Subjectivewellbeing improved significantly in allgroups (pb0.001; 27.6 points), and endpoint subjective wellbeing was not predicted bybaseline depression or anxiety, but by endpoint depression and anxiety.Conclusion: Interventions to improve subjective wellbeing should take into account the courseof mood state and anxiety. Assessment of subjective wellbeing and subjective quality of life inacute mania may need adapted tools.
Keywords:SchizophreniaBipolar disorderSubjective wellbeingQuality of lifeQuetiapine
1. Introduction
During the last decade, research on subjectivewellbeing inpatients with schizophrenia has demonstrated its clinicalimportance (Lambert et al., 2006a, 2007, 2008, 2009; Karowet al., 2007, Schimmelmann et al., 2007). Subjective wellbeingis highly positively correlated with quality of life (Lambertet al., 2009; Wehmeier et al., 2007a,b), it is a valuablepredictor of mid-term adherence with antipsychotic medica-tion in first- and multiple episode patients (Karow et al.,
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2007; Perkins et al., 2006), and early improvement insubjective wellbeing is a good predictor of short- and long-term symptomatic remission and overall recovery (de Haanet al., 2008; Lambert et al., 2007, 2008, 2009).
In schizophrenia, there is evidence for overlap betweenthe concepts of quality of life and subjective wellbeing.Studies have found congruence between subjective wellbeingand quality of life scales cross-sectionally as well as long-itudinally (e.g., with the Visual Analog Scale of the EuroQol-5D or with Heinrich's Quality of life scale, Karow et al., 2005;Lambert et al., 2009; Wehmeier et al., 2007b). Despite thegrowing body of literature on subjective wellbeing andquality of life, several questions remain unanswered to date:is it possible to use the concept of subjective wellbeing in
73M. Lambert et al. / Schizophrenia Research 110 (2009) 72–79
other psychotic disorders than schizophrenia includingschizoaffective and bipolar disorder, even in acute mania?How do different mood states and anxiety influence sub-jective wellbeing in the respective diagnostic groups?
The aims of this 6-month observational study were (i) tocompare different diagnostic groups, i.e. schizophrenia,schizoaffective disorder, and bipolar disorder with psychoticfeatures, with respect to baseline and course of subjectivewellbeing in a large sample of psychotic patients all treatedwith the second-generation antipsychotic quetiapine, and (ii)to investigate the specific impact of mood states and anxietyon baseline and course of subjective wellbeing in thesepsychotic disorders.
2. Methods
2.1. Context and sample
Data were collected in a 6-month, open label, prospectivepost authorisation survey (PAS), i.e. observational study. Thistype of non-interventional study is regulated by the GermanDrug Law (AMG), and the PAS protocol stipulated nointerventions different from daily routine treatment.
2175 outpatients with schizophrenia, schizoaffective dis-order, or bipolar disorder with psychotic features (henceforthbipolar disorder) diagnosed according to criteria of theInternational Classification of Diseases, 10th Revision (ICD-10; Dittmann and Dilling, 1990) were included in the study.Beside the diagnosis, inclusion criteria required that partici-pants be at least 18 years of age, with an IQN70 points, andeither switched to or started on quetiapine at study entry.These patients were in need for antipsychotic treatment and(i) antipsychotic-naïve at baseline or (ii) received otherantipsychotics being not adequately effective and/or notadequately tolerated. Private psychiatrists or psychiatrists inoutpatient centres treated all participating patients duringthe study period. These psychiatrists received at least 5 yearsof hospital-based training in psychiatry and are thereforewelltrained. Dosing was not regulated and solely determined bythe treating psychiatrist according to clinical effectivenessand tolerability. All patients were treated according to theGerman clinical practice guidelines for the treatment ofschizophrenia spectrum and bipolar disorder (Gaebel andFalkai, 2000, 2006). Due to the non-interventional nature ofthe study, quetiapine immediate release was prescribed asapproved on the German market (25 to 750 mg per day), andall other concomitant medications (i.e. mood-stabilizer,antidepressants, and/or benzodiazepines) were allowed.
2.2. Assessments and measures
Patients were assessed at baseline and at weeks 4, 12, and26 (endpoint) with standardized scales for severity of illnessand subjective wellbeing. Demographic and illness character-istics included age, gender, and diagnosis (according to ICD-10 criteria).
Severity of illness was assessed with the Clinical GlobalImpression Scale Severity-of-illness score (CGI-S; Guy, 1976).The CGI-S is a single item rated on a 7-point Likert scaleranging from 1 (not ill at all) to 7 (among the most extremelyill patients). The CGI-S scale is a valid, reliable instrument to
evaluate severity and treatment response in schizophrenia.Given its simplicity, brevity, clinical face validity, andconcurrent validity with the PANSS total score (Pearson-correlation: 0.76, Haro et al., 2003), the scale is appropriatefor use in observational studies. Improvement in the CGI wasdefined as “much” or “very much improved” in the CGI-Isubscale.
Mood state and anxietywere assessed at baseline bymeansof categorical variables, i.e. mood (depression, euthymia, ormania) and anxiety (yes, no). According to the protocol,clinicians had to rate depression, mania, and anxiety aspresent exclusively, if “the patients' mental state is clearlyimpaired” by the respective symptom/syndrome.
Subjective wellbeing was assessed with the SubjectiveWellbeing under Neuroleptic Treatment Scale (SWN-K,Naber et al., 2001; Lambert et al., 2007). The SWN-K, a self-rating Likert-scalewith six response categories (absent to verymuch), covers 20 statements (10 positive and 10 negative)with a minimum total score of 20 and a maximum total scoreof 120 points; higher scores indicate better wellbeing. TheSWN-K scale is highly concordant with various Quality of lifescales (e.g., EQ-VAS from the EuroQoL-5D [Prieto et al., 2003],Short-form 36 [SF-36; De Haan et al., 2002], or Heinrichs'Quality of Life Scale [QLS; r=0.71;Wehmeier et al., 2007a,b]).
2.3. Data analysis
All analyses were carried out using SPSS (version 14.0;Chicago, IL). Descriptive statistics were calculated for baselinevariables by chi-squared tests or ANOVAs. ANOVAs, whichyielded a significant F statistic were followed by a series ofpost hoc comparisons using the Games–Howell test whichtakes into consideration unequal sample sizes.
For statistical analysis of diagnostic group differencesregarding course of SWN-K total score over time, MixedModels Repeated Measures (MMRM) analyses were specified(Mallinckrodt et al., 2001, 2004). This likelihood-basedrepeated measures approach, which is similar to a repeatedmeasures ANOVA, has proven to be superior to e.g. lastobservation carried forward ANOVA in simulation scenariospatterned after acute phase neuropsychiatric clinical trials(Mallinckrodt et al., 2001, 2004) and is actively employed inschizophrenia research (Lambert et al., 2009). Linear modelslike MMRM report two main results, a ‘main effect’ and an‘interaction with time’ effect of a given independent variable(e.g. diagnostic subgroup) on the dependent variable (e.g.,SWN-K total score over time). In the latter example, the maineffect describes the average difference between diagnosticsubgroups across all post-baseline time points regarding theSWN-K total score. The ‘interaction with time’ effect detectswhether or not the difference in SWN-K total score betweendiagnostic subgroups varies with time.
3. Results
3.1. Subject characteristics
Demographic and clinical characteristics of the 2175patients are displayed in Table 1. The mean age was42.2 years, and 46.9% were male. 77.3% (n=1681) werediagnosed with schizophrenia or schizophreniform psychotic
Table 1Sample characteristics and baseline differences between diagnostic categories.
Socio-demographic andclinical characteristics
Totalsample(N=2175)
Diagnostic categories Statistics
Schizophrenia-spectrum(n=1681; 77.3% )
Schizoaffective disorder(n=249; 11.4%)
Bipolar disorder(n=245; 11.3%)
p-value
Baseline variablesGender, N (%), male 1020 (46.9) 818 (48.7) 100 (40.2) 102 (41.6) .009Age, Mean (SD) 42.2 (14.3) 41.4 (14.2) 44.1 (12.9) 45.5 (15.2) b .001CGI-Severity score, Mean (SD) 5.0 (0.9) 5.0 (0.9) 5.0 (1.0) 5.0 (0.9) .889Mood status, N (%)a b .001
Euthymic mood 1448 (66.6) 1375 (81.8) 61 (24.5) – a
Anxiety, N (%) 451 (20.7) 376 (22.4) 48 (19.3) 27 (11.0) b .001Substance Use Disorder (SUD), N (%) 444 (22.4) 331 (21.4) 50 (23.4) 63 (28.1) .072
Alcohol-related SUD 295 (13.6) 204 (12.1) 39 (15.7) 52 (21.2) b .001Other-related SUD 163 (7.5) 131 (7.8) 16 (6.4) 16 (6.5) .620
Reason for switch to quetiapine, N (%) b
Lack of efficacy 1162 (53.4) 895 (53.2) 153 (61.4) 114 (46.5) .004EPMS 437 (20.1) 360 (21.4) 51 (20.5) 26 (10.6) b .001Weight gain 553 (25.4) 433 (25.8) 82 (32.9) 38 (15.5) b .001
Subjective wellbeing at baselineSWN-K total score, Mean (SD) 60.9 (19.8) 57.7 (17.2) 64.2 (21.6) 79.5 (23.8) b .001
Abbreviations: CGI-S=Clinical Global Impressions-Severity of Illness scale, SWN-K=Subjective Wellbeing under Neuroleptic Treatment scale, short-version.EPMS=Extrapyramidal motor symptoms.aMissing values on mood-status in 12 patients (4.3%) with bipolar disorder.bMultiple answers possible.
74 M. Lambert et al. / Schizophrenia Research 110 (2009) 72–79
disorder (henceforth schizophrenia-spectrum),11.4% (n=249)with schizoaffective (41.4% depressed, 34.1% manic, 24.5%euthymic), and 11.3% with bipolar disorder (81.5% manic,18.5% depressed). Further, 22.4% fulfilled diagnostic criteriafor a co-morbid substance use disorder (henceforth SUD). Asoutlined in Table 1, patients with schizophrenia-spectrumwere more likely to be male (p=0.009) and younger(pb0.001) at baseline compared to patients with schizoaf-fective and bipolar disorder. Alcohol-related SUD (pb0.001)was more prevalent and anxiety (pb0.001) less prevalent atbaseline in patients with bipolar disorder compared topatients with schizophrenia-spectrum or schizoaffectivedisorder.
1510 patients (69.4%) were switched from anotherantipsychotic to quetiapine and 665 patients (30.6%), whowerewithout antipsychotic treatment within the last 4 weeksbefore baseline, were newly initiated on quetiapine. Atbaseline, the mean CGI-S total score was 5.0 points and themean SWN-K total scorewas 60.9 points indicating significantclinical and subjective impairment at baseline. During the 6-month study period, patients were treated with an averageadjusted quetiapine dose of 474.5mg per day (SD 230.2mg/d).Visit-wise mean dosages were as follows: week 4: 458.7 mg/d(SD 227.2 mg/d), week 12: 486.8 mg/d (SD 237.8 mg/d), andweek26: 475.7mg/d(SD236.5mg/d).No significant between-group differences were found.
3.2. Differences in course of subjective wellbeing acrossdiagnostic groups
While no significant differences regarding severity ofillness (CGI-S score) across diagnostic groups were detected
at baseline, patients’ subjective wellbeing at baseline asmeasured with the SWN-K total score was significantly worsein schizophrenia-spectrum (mean 57.7 points) compared tobipolar disorder (mean 79.5 points), with schizoaffectivedisorder taking the middle position (mean 64.1 points;ANOVA, all Games–Howell post-hoc tests significant at p-values between pb0.001 and p=.018).
Complete SWN-K data at baseline were available. Missingvalues in SWN-K scores at any time in the course of the studywere observed in 367 (16.9%) of the 2175 included patients.These 367 patients did not differ from those with completeSWN-K data regarding gender, diagnosis, co-morbid SUD,severity of illness as well as mood and anxiety status atbaseline. The SWN-K total score at baseline was significantly,yet minimally better in those with missing SWN-K follow-updata (63.7 versus 60.3 points; p=0.003). Since MMRMmakes use of all available data, the full data set was used foranalyses regarding the course of SNW-K. In the total sample, asignificant improvement in SWN-K total score from baselineto endpoint was detected (MMRM, significant time effect atpb0.001; mean change in observed cases [OC; n=1808]:27.6 points, SD 22.9 points). This significant improvement inSWN-K total score was first noted at the first post-baselinevisit (week 4; pb0.001), remaining significant throughoutthe complete follow-up period. Improvement of SWN-K totalscores was significantly different across diagnostic groupsafter controlling for SWN-K total scores at baseline (MMRM;main effect: pb0.001; interaction with time: pb0.001; seeFig. 1). SWN-K total score improvement was largest inpatients with schizophrenia-spectrum (adjusted meanchange: 29.5 points, confidence interval (CI)=28.4–30.6),followed by patients with schizoaffective disorder (24.4
Fig. 1. Course of the Subjective Wellbeing under Neuroleptic Treatment Scale total score across diagnostic groups of schizophrenia-spectrum, schizoaffective andbipolar disorder.
75M. Lambert et al. / Schizophrenia Research 110 (2009) 72–79
points, CI=21.5–27.3 points) and by bipolar disorder (14.3points, CI=11.3–17.2 points).
3.3. Effect of mood state and anxiety on baseline and course ofsubjective wellbeing
First, it was determined whether mood state and anxietywere associated with the baseline SWN-K total score bymeans of sequential linear regression analyses. Second,MMRM's were performed to assess the impact of moodstate and anxiety on the course of SWN-K total scores. Foraffective psychosis (i.e. bipolar and schizoaffective disorder),the impact of mood (i.e. depressed, euthymic, or manic) wasassessed, while for schizophrenia-spectrum, only the impactof depression was investigated (there were only 5 cases withmanic mood in schizophrenia-spectrum group). The impactof anxiety was assessed in both schizophrenia-spectrum andaffective psychosis (see Fig. 2).
Two sequential linear regression analyses were specifiedwith baseline SWN-K total score as the dependent and age,gender in step 1, the mood state in step 2, and anxiety in step3 as the independent (predictor) variables: (i) In schizo-phrenia-spectrum, depression (pb0.001) and anxiety(pb0.001) were independently associated with a worseSWN-K total score at baseline. Depression explained 2.3%and anxiety an additional 1.9% of baseline SWN-K variance(R2-change controlling for age and gender). (ii) In affectivepsychoses, depression versus mania (pb0.001), euthymiaversus mania (pb0.001), and anxiety (pb0.001) wereindependently associated with a worse SWN-K total score atbaseline. The mood status explained 24.0% and anxiety anadditional 4.1% of baseline SWN-K total score variance.Schizoaffective compared to bipolar disorder was significantlyassociated with a worse SWN-K total score at baseline(pb0.001) after controlling for age, gender, and mood/anxiety, explaining 2% of additional variance. The latter resultwas further explored: SWN-K total scores at baseline indepressed schizoaffective and depressed bipolar patientswere similar (mean 55.9, SD 16.9 vs. 56.1, SD 18.9), whilemanic schizoaffective patients were worse off at baselinecompared to manic bipolar patients (mean 75.0, SD 23.2 vs.85.1, SD 21.9).
Two MMRM's on the course of subjective wellbeingcontrolling for SWN-K total score at baseline, gender, andage revealed the following (Fig. 2 illustrates the findings ofthe MMRMs): (i) In schizophrenia-spectrum, patients withdepression or anxiety at baseline had a significantly worsecourse of SWN-K (depression: MMRM, main effect: pb0.001,interaction with time: pb0.005; anxiety: main effect:pb0.013, interaction with time: pb0.014). At endpoint,however, no significant differences between patients withor without depression or anxiety at baseline were detected.(ii) In affective psychosis, patients with depression comparedtomania and thosewith anxiety at baseline had a significantlyworse course of SWN-K (mood: main effect: pb0.001,interaction with time: pb0.001; anxiety: main effect:pb0.001, interaction with time: p=0.005). At 6-monthendpoint, however, no differences were found betweenpatients with depression or euthymia at baseline, andbetween patients with or without anxiety at baseline. Onlypatients with baseline mania compared to depression stillshowed a significantly better SWN-K total score at endpoint.
3.4. Effect of mood state and anxiety on subjective wellbeing atendpoint
Data on endpoint severity of depressed mood, manicmood or anxiety (assessed analogous to CGI-S) was availablein those subgroups of patients who were anxious, depressed,or manic at baseline, respectively. Since distribution ofseverity scores for manic mood was severely skewed, i.e.only very few patients (n=5) had severity scores of 4(moderately manic) or above, calculations for mania wereomitted from the following analyses. Two linear exploratoryregression analyses were specified to predict endpoint SWN-K total score by endpoint severity of depression and anxiety,each controlling for age, gender and diagnostic category.Endpoint severity of depressed mood was associated with theendpoint SWN-K total score, explaining additional 44.3% ofSWN-K total score variance (R2-change=0.443; F=189.9;β=−8.3, CI=−9.5 to −7.1; pb0.001). Also endpointseverity of anxiety was associated with the endpoint SWN-K total score, explaining additional 33.8% of the variance (R2-change=0.338; F=176.3; β=−7.9, CI=−9.1 to −6.7;
Fig. 2. (a) Baseline and course of SubjectiveWellbeing under Neuroleptic Treatment Scale (SWN-K) total score in patients with schizophrenia-spectrum disorderswith or without depression at baseline and with or without anxiety at baseline. (b) Baseline and course of SWN-K total score in patients with affective psychoses(i.e. schizoaffective and bipolar disorder) according tomood at baseline (depressed, euthymic, or manic) andwith or without anxiety at baseline. Due to the impactof mood on course of SWN-K, the anxiety values were adjusted for mood state.
76 M. Lambert et al. / Schizophrenia Research 110 (2009) 72–79
pb0.001). In other words, endpoint severity of depressionand anxiety was associated with low subjective wellbeing atendpoint.
4. Discussion
To the authors' knowledge, the present study is the first toinvestigate and compare subjective wellbeing across differentdiagnostic groups of psychotic disorders and the first to assessthe effects of mood state and anxiety on baseline and courseof subjective wellbeing. As subjective wellbeing is highlycorrelated with quality of life and adherence with medication(Karow et al., 2007; Wehmeier et al., 2007a,b), these findingshave important clinical implications.
During the 6-month study period, there was a significantimprovement in SWN-K total score from baseline to endpointin all diagnostic categories (SWN-K mean change: 27.6points). The extent of mean change in SWN-K total score in
the schizophrenia-spectrum group (29.5 points) was compar-able to the results of two previous 3-month studies (Lambertet al., 2006b: mean change of 22.1 points; Lambert et al.,2007: mean change of 28.5 points).
4.1. Key findings
At study entry, despite similar illness severity, patientswith schizophrenia-spectrum (SWN-K: 57.7 points) displayeda significantly lower subjective wellbeing score than patientswith schizoaffective (64.1 points) or bipolar disorder (79.5points). These baseline subjective wellbeing differencesbetween diagnostic groups were further explored and maybe related to the following findings: (i) The mood status washighly associated with subjective wellbeing at baseline inaffective psychoses, i.e. bipolar and schizoaffective disorder,with high SWN-K scores in manic (82 points) compared todepressed (56.1 points) and euthymic (64.8 points) patients.
77M. Lambert et al. / Schizophrenia Research 110 (2009) 72–79
Mood status explained 24% of the SWN-K total score varianceat baseline in affective psychoses. Previous studies focusingon the impact of different mood states on quality of life inbipolar disorder have only assessed patients with euthymic ordepressed mood or patients with only mild (hypo)manicsymptoms, or only focused on the influence of different moodstates on objectively assessed functioning level (Gazalle et al.,2007; Simon et al., 2007; Zhang et al., 2006). Interestingly,subjective wellbeing at baseline in manic patients withschizoaffective disorder (SWN-K: 75.0 points) was worsethan in manic patients with bipolar disorder (85.1 points).Amongst others, this is possibly related to a comparablyhigher severity of psychotic symptoms (Benabarre et al.,2001), a more severe cognitive impairment (Torrent et al.,2007), and a lower functioning level (Gupta et al., 2007) inschizoaffective disorder compared to bipolar disorder. (ii) Adifferential influence of concurrent anxiety on subjectivewellbeing at baseline was detected in schizophrenia-spec-trum compared to affective psychoses with 1.9% explainedvariance in schizophrenia-spectrum and 4.1% in bipolar andschizoaffective disorder. Contrary to schizophrenia-spectrum(SWN-K: 53 versus 59 points), concurrent anxiety in affectivepsychosis resulted in a significantly worse subjective well-being score (SWN-K: 59.9 versus 73.9 points), even aftercontrolling for mood state at baseline. These findings areconsistent with previous studies, which have repeatedlyfound that anxiety in bipolar disorder is related to a poorquality of life (Albert et al., 2008; Kauer-Sant'Anna et al.,2007). This association is also known for patients withschizophrenia (Braga et al., 2005; Huppert et al., 2001),which was not detected in this study, potentially due to thegenerally lower subjective wellbeing scores in schizophrenia-spectrum.
In line with previous studies, patients with schizophrenia-spectrum displayed a poor subjective wellbeing at baseline(SWN-K: 57.7 points) corresponding to impaired quality of life(Lambert et al., 2006a, 2007). However, bipolar or schizoaf-fective depression (SWN-K: 56.1 points) was also associatedwith severely impaired subjective wellbeing at baseline, andeven patients with euthymic mood displayed a relatively lowsubjectivewellbeing score (SWN-K: 64.8 points; Gazalle et al.,2007; Zhang et al., 2006). These results are important asprevious studies have shown that even modest changes inseverity of depression in patients with bipolar disorder areassociated with clinically significant changes in functionalimpairment and disability (Gazalle et al., 2006; Simon et al.,2007). Previous assumptions that clinically stabilized patientswith schizophrenia generally have a lower quality of life thanpatients with stabilized bipolar disorder (Chand et al., 2004)are not supported by this study.
While depression and anxiety was related to baselinesubjective wellbeing, endpoint subjective wellbeing level wasneither predicted by baseline depression nor by anxiety inaffective or in non-affective psychoses. This is most likelyexplained by the assumption that simultaneous rather thanprevious mood and anxiety influences subjective wellbeing inpsychotic patients. The latter is supported by the finding thatendpoint severity of depression in those depressed at baselineas well as endpoint severity of anxiety in those anxious atbaseline was highly associated with endpoint subjectivewellbeing. However, the fact that severity data was available
only in these subgroups of patients renders a cautiousinterpretation of this finding mandatory.
4.2. Limitations
As this was a large observational study in daily clinicalpractice conducted at many sites, several methodologicallimitations such as the lack of assessment of inter-raterreliability were unavoidable. Another limitation is the lack ofassessment of mood and anxiety as continuous variables inthe total sample. Additionally, it would have been ofparticular interest to assess the impact of course of moodstate on course of subjective wellbeing across all diagnosticsubgroups, but these variables were not available in thisstudy. Further, as mania is additionally categorized aseuphoric and dysphoric mania (e.g., Dilsaver et al., 1999)and dysphoric mania is possibly more likely in patients withschizoaffective compared to bipolar disorder (Benabarreet al., 2001), these variables should be taken into account infuture studies. The fact that the present trial was not blindedshould not influence results as the main outcome was asubjective measure. Furthermore, generalizability of theresults to epidemiological or first-episode samples is limitedby the selection of an outpatient population with initiation ofnew or switch to quetiapine treatment. Strengths of thepresent investigation were the large sample size and, incontrast to most previous studies on subjective wellbeing, thehomogeneity of antipsychotic treatment.
4.3. Conclusions
Our results suggest that it may be questionable to use thissubjective wellbeing scale, and potentially many othersubjective quality of life scales in acute mania. Our resultsshow that “good” subjective wellbeing in manic patients maysubstantially mirror the pathological euphoric mood state,which is unlikely to represent true good quality of life andwellbeing under antipsychotics. Future studies should there-fore focus on longitudinal analyses of the course of mood statein acute mania and its relation to the course of subjective andobjective quality of life. Notably, baseline depression as wellas anxiety had only a small predictive value on the course ofsubjective wellbeing, while rather endpointmood and anxietyexplained endpoint subjective wellbeing. Whether this is dueto the antidepressive and anxiolytic effects of quetiapine isbeyond the scope of the study's non-RTC design, particularlyas information on the influence of concomitant medicationsuch as mood stabilizer and antidepressants was not availablein this study. In light of the high lifetime risk of anxiety anddepression in psychotic disorders (Braga et al., 2005; Keller,2006), it may be advisable to treat these patients withantipsychotics being also effective against other psychopatho-logical dimensions aside from psychotic symptoms, i.e.antidepressive, mood-stabilizing, and anxiolytic effects (e.g.,Dorée et al., 2007; Hirschfeld et al., 2006; Keating andRobinson, 2007). Yet, our findings need to be extended bylongitudinal studies on the interaction between course ofdepression/anxiety and subjective wellbeing/quality of life.The role, specific antipsychotics may play in this interaction,needs to be further elucidated by randomized controlledtrials.
78 M. Lambert et al. / Schizophrenia Research 110 (2009) 72–79
Role of funding sourceThis observational study was funded and conducted by AstraZeneca,
Germany. AstraZeneca had no role in developing the research question anddata analysis strategy, analyzing the raw data, interpreting the data, orwriting the manuscript. AstraZeneca had the right to comment on the finaldraft of this manuscript before submission to the Journal. AstraZenecaapproved the manuscript unchanged.
ContributorsThe first and senior author (ML and BGS) developed the research
question and data analysis strategy, had access to the raw-data, analyzed thedata, interpreted the data, and wrote the manuscript. Authors JK and JH areemployees of the Medical Neuroscience Department of AstraZenecaGermany and contributed to the original design and conduct of the study.All authors have read and contributed to the final version of the manuscript.
Conflict of InterestAuthors ML, BGS, DN, AK, and CGH have received educational grants and
are on the speakers' board of AstraZeneca. Authors JK and JH are employeesof the Medical Neuroscience Department of AstraZeneca Germany. None ofthe authors have more substantial associations with AstraZeneca, Germany.
AcknowledgementsThe authors wish to express their gratitude to all participating patients
and physicians.
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