Consistency of atypical antipsychotic superiority to placebo in recent clinical trials.
BACKGROUND
The use of control placebos in clinical trials of new antipsychotic medications is increasingly under examination. The active controlled equivalence study could offer a potential alternative design. First, however, it must be clear that any proposed standard control agent has been consistently superior to placebo in previous studies.


METHODS
Through a Freedom of Information Act request, we identified nine placebo-controlled trials of risperidone, olanzapine, or quetiapine.


RESULTS
Meta-analysis indicated that the pooled estimate of the true population effect size +/- SE was 0.46 +/- 0.06 for categorical response rates and >0.53 +/- 0.07 for the continuous Brief Psychiatric Rating Scale change score outcome measure. If the desired detectable effect size is set very conservatively at a 95% confidence lower bound for the estimate of true effect size, statistical power for random samples of 80 per group drawn from a population of subjects similar to that of the nine meta-analyzed studies is.67 for categorical response rates and >.82 for the continuous measure, based on one-sided alpha =.05.


CONCLUSIONS
These data suggest substantial confidence that a therapeutic dose of an atypical antipsychotic will be statistically superior to placebo in an adequately sized randomized trial, when reporting a continuous measure as the principal outcome.
Woods
S W
SW
Treatment Research Program, Connecticut Mental Health Center, New Haven, CT 06519, USA.
Stolar
M
M
Sernyak
M J
MJ
Charney
D S
DS
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines; D002986:Clinical Trials as Topic; D003987:Dibenzothiazepines / Q000627:therapeutic use; D006801:Humans; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy*; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000627:therapeutic use
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D010890:Pirenzepine; D018967:Risperidone; D000077152:Olanzapine