@article{9015b46995a14dce88d28cb469a34f71,
title = "Reappraising the variability of effects of antipsychotic medication in schizophrenia: a meta-analysis",
abstract = "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 384 individuals who were administered antipsychotic treatment and 88 who received placebo) 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) (ρ=-0.32, p=0.002 and ρ=-0.39, p<0.001, respectively). Using the most conservative of these estimates, a meta-analysis of treatment effect heterogeneity provided evidence of a marked variability in antipsychotic-specific effects between individuals with schizophrenia, with the top quartile of patients experiencing beneficial treatment effects of 17.7 points or more on the PANSS total score, while the bottom quartile presented a detrimental effect of treatment relative to placebo. This evidence of clinically meaningful treatment effect heterogeneity suggests that efforts to personalize antipsychotic treatment of schizophrenia have potential for success.",
author = "McCutcheon, {Robert A} and Toby Pillinger and Orestis Efthimiou and Marta Maslej and Mulsant, {Benoit H} and Young, {Allan H} and Andrea Cipriani and Howes, {Oliver D}",
note = "Funding Information: R.A. McCutcheon is supported by the UK National Institute for Health Research (NIHR); T. Pillinger by the NIHR and Maudsley Charity; M. Maslej by a post‐doctoral fellowship from the Canadian Institutes of Health Research (CIHR); O. Efthimiou by the Swiss National Science Foundation (Ambizione grant no. 180083); B.H. Mulsant by the Labatt Family Chair in Biology of Depression in Late‐Life Adults at the University of Toronto, the US National Institute of Mental Health and the US Patient‐Centered Outcomes Research Institute. A. Cipriani is supported by the NIHR Oxford Cognitive Health Clinical Research Facility, an NIHR Research Professorship (grant no. RP‐2017‐08‐ST2‐006), the NIHR Oxford and Thames Valley Applied Research Collaboration and the NIHR Oxford Health Biomedical Research Centre (grant no. BRC‐1215‐20005). O.D. Howes is supported by the UK Medical Research Council (grant no. MC_A656_5QD30_2135), the Maudsley Charity (grant no. 666), the Wellcome Trust (grant no. 094849/Z/10/Z) and the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. https://zenodo.org/record/5896334#.Ye5UQljP2rM . The views expressed are those of the authors and not necessarily those of the funding bodies. Supplementary information on the study is available at Funding Information: R.A. McCutcheon is supported by the UK National Institute for Health Research (NIHR); T. Pillinger by the NIHR and Maudsley Charity; M. Maslej by a post-doctoral fellowship from the Canadian Institutes of Health Research (CIHR); O. Efthimiou by the Swiss National Science Foundation (Ambizione grant no. 180083); B.H. Mulsant by the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto, the US National Institute of Mental Health and the US Patient-Centered Outcomes Research Institute. A. Cipriani is supported by the NIHR Oxford Cognitive Health Clinical Research Facility, an NIHR Research Professorship (grant no. RP-2017-08-ST2-006), the NIHR Oxford and Thames Valley Applied Research Collaboration and the NIHR Oxford Health Biomedical Research Centre (grant no. BRC-1215-20005). O.D. Howes is supported by the UK Medical Research Council (grant no. MC_A656_5QD30_2135), the Maudsley Charity (grant no. 666), the Wellcome Trust (grant no. 094849/Z/10/Z) and the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The views expressed are those of the authors and not necessarily those of the funding bodies. Supplementary information on the study is available at https://zenodo.org/record/5896334#.Ye5UQljP2rM. Publisher Copyright: {\textcopyright} 2022 World Psychiatric Association.",
year = "2022",
month = jun,
day = "2",
doi = "10.1002/wps.20977",
language = "English",
volume = "21",
pages = "287--294",
journal = "World Psychiatry",
issn = "1723-8617",
publisher = "Wiley-Blackwell",
number = "2",
}