Limitations of controlled augmentation trials in schizophrenia.

To assess the empirical basis for add-on augmentation treatments in schizophrenia, this study examined the experimental design components of pharmacologic augmentation trials in schizophrenia and compared them to conventional requirements. A search covering a 5-year period (1988-1992) identified 13 double-blind, placebo-controlled, parallel, add-on neuroleptic augmentation drug trials. The mean number of subjects per trial was 34.5, and the mean number of outcome measures examined was 25.0. The probability for a significant finding by chance was 63%. Mean effect size required to achieve conventional statistical power was 1.6. Mean statistical power (for effect sizes of .5-1.0) was .1-.4. The mean number of subjects actually required for power of .80 was 58-216. The majority of the 13 trials included too few patients and employed too many outcome measures to conclusively prove or disprove therapeutic efficacy. Conclusions drawn from such trials with less than 40-100 subjects or more than one hypothesis must remain tentative at best.