The response of subgroups of patients with schizophrenia to different antipsychotic drugs: a systematic review and meta-analysis

Background As comparatively few trials in subgroups of patients with schizophrenia have been done, clinicians need to know whether they can rely on the results of randomised controlled trials (RCTs) in the general population of patients with schizophrenia. We aimed to compare the efficacy and side-effects of antipsychotic drugs in different subgroups. Methods In this systematic review and meta-analysis, we searched reference lists of previous systematic reviews and meta-analyses, the Cochrane Schizophrenia Group's Study-Based Register (from database inception to April 27, 2020), and PubMed (from April 1, 2020 to June 14, 2021). We excluded studies in patients with stable schizophrenia (ie, relapse prevention studies), studies with a high risk of bias, and studies from mainland China due to quality concerns concerning allocation and masking methods. We included single-blind RCTs or better that assessed one or more of 16 second-generation and 18 first-generation antipsychotics in the general population of patients with schizophrenia or in one or more of the subgroups: children and adolescents (age range as defined in the original studies), patients with a first episode, patients with predominant or prominent negative symptoms, patients with comorbid substance use, patients with treatment-resistant schizophrenia, or older patients (age range as defined in the original studies). Two authors independently screened the results of the search, retrieved full-text articles, and checked the inclusion criteria. Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline, all parameters were extracted in duplicate. The primary outcome was change in overall symptoms. We compared drug efficacy between subgroups, by sex, schizoaffective disorder versus schizophrenia, and study origin using random-effects, inverse variance meta-analyses and random-effects subgroup tests, and meta-regression. Findings We included 537 RCTs with 76 382 participants, 26 627 (34·9%) women, 49 755 (65·1%) men, mean age 37·3 years (range of means 7·9–80·2; ethnicity data not available). 412 RCTs included patients in the general population of patients with schizophrenia, 42 included patients with treatment-resistant schizophrenia, 25 included children and adolescents, 20 included patients with their first episode, 20 included patients with predominant or prominent negative symptoms, 13 included patients with comorbid substance use, and 11 included older patients. Of 507 random-effects subgroup tests done, 46 (9%) showed a significant difference (p<0·05) between subgroups, but there was no clear indication as to which drug should be used in which subgroup. Interpretation The effects of antipsychotics in various patient subgroups were usually similar to those in the general population of patients with schizophrenia, but comparably few studies contributed to the subgroups, in particular in terms of side-effects. If the evidence for treatment in a given subgroup is small, guideline makers and clinicians should consider using the results in the much better studied group of the general population of patients with schizophrenia. Funding German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung; FKZ 01KG1508)