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Original Investigation
June 3, 2019

Evaluation of Differences in Individual Treatment Response in Schizophrenia Spectrum Disorders: A Meta-analysis

Author Affiliations
  • 1Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York
  • 2Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, New York
  • 3Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, New York
  • 4University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
  • 5Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany
JAMA Psychiatry. 2019;76(10):1063-1073. doi:10.1001/jamapsychiatry.2019.1530
Key Points

Question  Is there evidence from randomized clinical trials that patients respond differently to antipsychotic drugs?

Findings  In this meta-analysis of 52 randomized clinical trials involving 15 360 patients with a schizophrenia or schizoaffective diagnosis, the outcome variability in the antipsychotic drug treatment group was not higher but slightly lower than that in the placebo control group.

Meaning  This study cannot rule out that individual differences in drug response might still exist, but it does question the assumption of a personal element of response to antipsychotic treatment.


Importance  An assumption among clinicians and researchers is that patients with schizophrenia vary considerably in their response to antipsychotic drugs in randomized clinical trials (RCTs).

Objective  To evaluate the overall variation in individual treatment response from random variation by comparing the variability between treatment and control groups.

Data Sources  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.

Study Selection  Double-blind, placebo-controlled, RCTs of adults with a diagnosis of schizophrenia spectrum disorders and prescription for licensed antipsychotic drugs.

Data Extraction and Synthesis  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.

Main Outcomes and Measures  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.

Results  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).

Conclusions and Relevance  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.