Reappraising the variability of effects of antipsychotic medication in schizophrenia: a meta-analysis

It is common experience for practising psychiatrists that individuals with schizophrenia vary markedly in their symptomatic response to antipsychotic medication. What is not clear, however, is whether this variation reflects variability of medication-specific effects (also called “treatment effect heterogeneity”), as opposed to variability of non-specific effects such as natural symptom fluctuation or placebo response. Previous meta-analyses found no evidence of treatment effect heterogeneity, suggesting that a “one size fits all” approach may be appropriate and that efforts at developing personalized treatment strategies for schizophrenia are unlikely to succeed. Recent advances indicate, however, that earlier approaches may have been unable to accurately quantify treatment effect heterogeneity due to their neglect of a key parameter, the correlation between placebo response and medication-specific effects. In the present paper, we address this shortcoming by using individual patient data and study- level data to estimate that correlation and quantitatively characterize antipsychotic treatment effect heterogeneity in schizophrenia. Individual patient data (on 88 individuals who received placebo and 384 who were administered antipsychotic treatment) were obtained from the Yale University Open Data Access (YODA) database. Study-level data were obtained from a meta- analysis of 66 clinical trials including 17,202 patients. Both individual patient and study-level analyses yielded a negative correlation between placebo response and treatment effect for the total score on the Positive and Negative Syndrome Scale (PANSS) (=–0.32, p=0.002 and =–0.39, p