Evaluation of Differences in Individual Treatment Response in Schizophrenia Spectrum Disorders

Abstract

An assumption among clinicians and researchers is that patients with schizophrenia vary considerably in their response to antipsychotic drugs in randomized clinical trials (RCTs). To evaluate the overall variation in individual treatment response from random variation by comparing the variability between treatment and control groups. Cochrane Schizophrenia, MEDLINE/PubMed, Embase, PsycINFO, Cochrane CENTRAL, BIOSIS Previews, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform from January 1, 1955, to December 31, 2016. Double-blind, placebo-controlled, RCTs of adults with a diagnosis of schizophrenia spectrum disorders and prescription for licensed antipsychotic drugs. Means and SDs of the Positive and Negative Syndrome Scale pretreatment and posttreatment outcome difference scores were extracted. Data quality and validity were ensured by following the PRISMA guidelines. The outcome measure was the overall variability ratio of treatment to control in a meta-analysis across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. A personal element of response was hypothesized to be reflected by a substantial overall increase in variability in the treatment group compared with the control group. An RCT was simulated, comprising 30 patients with schizophrenia randomized to either the treatment or the control group. The different components of variation in RCTs were illustrated with simulated data. In addition, we assessed the variability ratio in 52 RCTs involving 15 360 patients with a schizophrenia or schizoaffective diagnosis. The variability was slightly lower in the treatment compared with the control group (variability ratio = 0.97; 95% CI, 0.95-0.99; P = .01). In this study, no evidence was found in RCTs that antipsychotic drugs increased the outcome variance, suggesting no personal element of response to treatment but instead indicating that the variance was slightly lower in the treatment group than in the control group; although the study cannot rule out that subsets of patients respond differently to treatment, it suggests that the average treatment effect is a reasonable assumption for the individual patient.