Standard versus reduced dose of antipsychotics for relapse prevention in multi-episode schizophrenia: a systematic review and meta-analysis of randomised controlled trials

Background Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is unclear. We aimed compare risks and benefits reduced versus standard doses antipsychotics. Methods searched Embase, Medline, PsycINFO, the Cochrane Library from database inception until June 17, 2020, randomised trials adults or schizoaffective disorder lasting at least 24 weeks, including clinically stable baseline, comparing two same antipsychotic, excluding first-episode psychosis treatment-resistant schizophrenia. compared low-dose (within 50–99% lower limit dose) very-low dose (less than 50% limit) dose, defined as higher recommended by International Consensus Study. Data published reports on number participants, treatment, sex, age, events, changes psychopathology scores were extracted independently authors. Investigators sponsors contacted email obtain missing information regarding outcomes. Co-primary outcomes relapse all-cause discontinuation. Study-level data meta-analysed using random-effects models, calculating risk ratios (RRs) dichotomous data, Hedges' g continuous data. The protocol was registered OSF registries. Findings 7853 references identified search one additional reference a manual review relevant studies. 5744 abstracts assessed eligibility, 101 full-text review. Of these, 79 excluded variety reasons, resulting 22 studies being included meta-analysis, reporting 3282 individuals. Study participants had median age 38 years (IQR 36–40) 2166 (65·9%) males 1116 (34·0%) females. Compared low increased 44% (16 trials, 1920 participants; RR 1·44, 95% CI 1·10–1·87; p=0·0076; I2=46%) discontinuation 12% 1932 1·12, 1·03–1·22; p=0·0085; I2=0%). Very 72% (13 2058 1·72, 1·29–2·29; p=0·0002; I2=70%) 31% (11 1866 1·31, 1·11–1·54; p=0·0011; I2=63%). very did not significantly increase (five 686 0·96–1·79; p=0·092; I2=51%) 1·11, 0·95–1·30; p=0·18; I2=43%). Subgroup analyses double-blind open-label studies, first-generation second-generation antipsychotics, oral long-acting injectable antipsychotics consistent overall results. Most classified having some concerns bias assessment, which mainly caused absence publicly available study registrations. Interpretation During multi-episode schizophrenia, should probably below range acute stabilisation, because reducing further associated an both Funding None