Sex selection bias in schizophrenia antipsychotic trials.

The sex prevalence of schizophrenia is approximately equal, and yet clinical trials of new therapeutic drugs have been conducted, for the most part, with male participants. The authors reviewed the percentage of women in schizophrenia clinical trials of the new "atypical" antipsychotic medications. MEDLINE and Cochrane databases were searched for English-language randomized controlled trials involving risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. Studies with a sample size of more than 50 and a subject diagnosis of schizophrenia, schizophrenia spectrum disorder, or broad psychosis were included for review. For each study, the following items were abstracted: source of support, pharmacotherapy, site location, treatment setting, patient phase, psychotic episode number, duration, number of men and women in the total sample, mean age of the sample, and the presence of women-specific inclusion/exclusion criteria. Sixty-seven published studies met criteria. The median percentage of women in the total sample was 33.3%, the minimum was 6.7%, and the maximum was 71.2%. A stepwise linear regression analysis showed that age (younger samples), center location (Unites States and Canada), treatment patient setting (inpatient), and ziprasidone trials were all associated with relatively lower percentages of women. Sex differences in antipsychotic pharmacokinetics and pharmacodynamics that may result in differential effectiveness and susceptibility to adverse effects cannot be ascertained when the percentage of women in clinical trials is as low as it is. The increasing shift toward outpatient rather than inpatient drug trials may help to increase the proportion of women.