Dropout rates in placebo-controlled and active-control clinical trials of antipsychotic drugs: a meta-analysis.
BACKGROUND
Dropout rates in randomized clinical trials of antipsychotic drugs have consistently been reported to be high, and the use of a placebo-controlled design is hypothesized to be one of the reasons for this.


OBJECTIVE
To investigate this hypothesis in a meta-analysis of available data from pertinent clinical trials.


METHODS
Comprehensive search of PubMed- and MEDLINE-listed journals.


METHODS
Double-blind randomized controlled clinical trials of the second-generation antipsychotics risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, and aripiprazole meeting the following criteria: unselected patient population with a diagnosis of schizophrenia or schizoaffective disorder, change in psychopathologic symptoms as the primary end point, and trial duration of 12 weeks or less.


METHODS
Sample size, mean age, baseline disease severity, dropout rate, trial design, trial duration, and publication year.


RESULTS
Thirty-one trials meeting the inclusion criteria were found, comprising 10 058 subjects. Weighted mean dropout rates in the active treatment arms were significantly higher in placebo-controlled trials (PCTs) than in active-control trials: 48.1% (PCTs) vs 28.3% (active-control trials) for second-generation antipsychotics (odds ratio, 2.34; 95% confidence interval, 1.58-3.47) and 55.4% (PCTs) vs 37.2% (active-control trials) for classical antipsychotics (odds ratio, 2.10; 95% confidence interval, 1.29-3.40). Within PCTs, attrition rates were significantly higher in the placebo arms than with second-generation antipsychotics (60.2% vs 48.1%; odds ratio, 1.63; 95% confidence interval, 1.37-1.94). Within the subset of trials in which both second-generation and classical antipsychotics were used, dropout rates were significantly higher with classical antipsychotics.


CONCLUSIONS
Use of a placebo-controlled design had a major effect on the dropout rates observed. Because high dropout rates affect the generalizability of such studies, it is suggested that, in addition to the PCTs, studies with alternative designs need to be considered when evaluating an antipsychotic's clinical profile.
Kemmler
Georg
G
Department of General Psychiatry, Innsbruck University Clinics, Anichstrasse 35, A-6020 Innsbruck, Austria. georg.kemmler@uibk.ac.at
Hummer
Martina
M
Widschwendter
Christian
C
Fleischhacker
W Wolfgang
WW
D014150:Antipsychotic Agents / Q000145:classification / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D016017:Odds Ratio; D010352:Patient Dropouts / Q000706:statistics & numerical data*; D010919:Placebos; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000523:psychology; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design; D018401:Sample Size; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010919:Placebos