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Comment & Response
November 24, 2021

Limitations in Research on Maintenance Treatment for Individuals With Schizophrenia—Reply

Author Affiliations
  • 1Department of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, Germany
  • 2Institute of Psychiatry, Psychology and Neuroscience, Department of Psychiatry, Department of Psychosis Studies, King’s College London, London, United Kingdom
  • 3Psychiatric Institute, University of Illinois at Chicago
  • 4Johns Hopkins University, Baltimore, Maryland
JAMA Psychiatry. Published online November 24, 2021. doi:10.1001/jamapsychiatry.2021.3403

In Reply Replication is the essence of science. It is therefore important that Højlund and colleagues,1 who used a different meta-analytic method and slightly different inclusion criteria from ours, had similar findings in that standard doses (in our analysis, 5 mg risperidone equivalent) were more effective than lower ones (also see our Supplement where we applied the same type of analysis2). Our results can be interpreted in the way Højlund et al suggest in their Letter. What dose-response meta-analysis adds is the shape of the dose response curve. As for acute schizophrenia,3 we found a hyperbolic pattern, meaning that doses higher than 5 mg/d risperidone equivalent were not associated with greater efficacy.2 Moreover, increasingly lower doses are associated with increasingly higher risk of relapse, with the risk of relapse becoming disproportionately higher the lower the dose becomes. This means that doses should be reduced in a hyperbolic pattern (ie, reductions by smaller and smaller amounts) if any changes are made, because the safest course is typically to maintain a standard dose.4 Moreover, the hyperbolic shape of the dose-response curve speaks against an average minimum effective antipsychotic dose, unless one defines the amount of efficacy by an arbitrary threshold. Efficacy does not stop abruptly; even small doses such as 2.5 mg risperidone equivalent per day are somewhat more effective than placebo. And there is so much interindividual variability that each patient has an individual minimum effective dose rather than conforming to a general threshold.

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