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The efficacy and heterogeneity of antipsychotic response in schizophrenia: A meta-analysis

Molecular Psychiatry volume 26, pages 1310–1320 (2021)Cite this article

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Abstract

The response to antipsychotic treatment in schizophrenia appears to vary, and as such it has been proposed that different subtypes of schizophrenia exist, defined by treatment-response. This has not been formally examined using meta-analysis. Randomised controlled trials comparing placebo and antipsychotics in acute treatment of schizophrenia listed in PubMed, EMBASE and PsycINFO from inception until 30 November 2018 were examined. Relative variability of symptomatic improvement in antipsychotic-treated individuals compared to placebo-treated individuals was quantified using coefficient of variation ratio (CVR). Mean difference in symptom change was quantified using Hedges’ g. In addition, individual patient data from two clinical trials was examined in terms of both the distribution of total symptom change, and the variability of individual symptoms and symptom factors. In total, 11,006 articles were identified. Sixty six met inclusion criteria, reporting on 17,202 patients. Compared with placebo, antipsychotic-treated patients demonstrated greater total symptom improvement (g = 0.47, p < 0.001) and reduced variability in symptomatic improvement for total (CVR = 0.86, p < 0.001), positive (CVR = 0.89, p < 0.001), and negative symptoms (CVR = 0.86, p = 0.001). Lower variability in antipsychotic-response relative to placebo was associated with studies published earlier (z = 3.98, p < 0.001), younger patients (z = 3.07, p = 0.002), higher dose treatments (z = −2.62, p = 0.009), and greater mean-difference in symptom-change (z = −5.70, p < 0.001). In the individual patient dataset (N = 522 patients), antipsychotic treated patients did not show significantly increased variability for any individual symptom, and there was no evidence of a bimodal distribution of response. Compared to placebo, antipsychotic treatment shows greater improvement and lower variability of change in total, positive and negative symptoms. This is contrary to the hypothesis that there is a subtype of antipsychotic non-responsive schizophrenia. Instead our findings, provide evidence for a relatively homogeneous effect of antipsychotic treatment in improving symptoms of schizophrenia.

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Acknowledgements

RM’s work is supported by a clinical research training fellowship grant from the Wellcome trust (no. 200102/Z/15/Z). OH’s work is supported by Medical Research Council-UK (no. MC-A656-5QD30), Maudsley Charity (no. 666), Brain and Behavior Research Foundation, and Wellcome Trust (no. 094849/Z/10/Z) grants, and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

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Author notes

  1. These authors contributed equally: Robert A. McCutcheon, Toby Pillinger

Authors and Affiliations

  1. Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, De Crespigny Park, London, SE5 8AF, UK

    Robert A. McCutcheon, Toby Pillinger, Yuya Mizuno, Tiago Reis Marques & Oliver D. Howes

  2. Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, London, W12 0NN, UK

    Robert A. McCutcheon, Toby Pillinger, Yuya Mizuno, Tiago Reis Marques & Oliver D. Howes

  3. Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, W12 0NN, UK

    Robert A. McCutcheon, Toby Pillinger, Yuya Mizuno, Tiago Reis Marques & Oliver D. Howes

  4. South London and Maudsley NHS Foundation Trust, London, UK

    Robert A. McCutcheon, Toby Pillinger, Yuya Mizuno, Adam Montgomery, Haridha Pandian, Luke Vano, Tiago Reis Marques & Oliver D. Howes

  5. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, 160-8582, Japan

    Yuya Mizuno

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Contributions

Study conception: RM, TP,YM, OH; Study design: RM, TP, YM, AM, HP, LV, OH; Data searching and extraction: RM, TP, YM, AM, HP, LV; Data analysis: RM Data interpretation: RM, TP, YM, OH; Writing of manuscript: RM, TP, YM, AM, HP, LV, OH.

Corresponding author

Correspondence to Oliver D. Howes.

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Conflict of interest

RM, TP, AM, HP and LV declare no financial conflicts of interest. YM has received manuscript fees or speaker’s honoraria from Sumitomo Dainippon Pharma and Yoshitomi Yakuhin, fellowship grants from Japan Society for the Promotion of Science, Astellas Foundation for Research on Metabolic Disorders, Japanese Society of Clinical Neuropsychopharmacology, and Mochida Memorial Foundation for Medical and Pharmaceutical Research, and consultant fees from Bracket within the past three years. ODH has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Astra-Zeneca, Autifony, BMS, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand and Roche. Neither ODH or his family have been employed by or have holdings/a financial stake in any biomedical company.

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McCutcheon, R.A., Pillinger, T., Mizuno, Y. et al. The efficacy and heterogeneity of antipsychotic response in schizophrenia: A meta-analysis. Mol Psychiatry 26, 1310–1320 (2021). https://doi.org/10.1038/s41380-019-0502-5

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