Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia

作者：Stefan Leucht, Sofía Bauer, Spyridon Siafis, Tasnim Hamza, Hui Wu, Johannes Schneider‐Thoma, Georgia Salanti, John M. Davis · 发表于：JAMA Psychiatry · 年份：2021 · DOI：10.1001/jamapsychiatry.2021.2130 · 被引用次数：97 · 研究领域：Schizophrenia research and treatment、Healthcare Decision-Making and Restraints、Tryptophan and brain disorders

Importance: The doses of antipsychotic drugs needed for relapse prevention in schizophrenia is a debated issue. Objective: To examine dose-response findings in a meta-analysis of randomized clinical trials. Data Sources: Studies were identified through the Cochrane Schizophrenia Group's Study-Based Register of Trials (March 9, 2020), PubMed (January 1, 2021), and previous reviews. First authors and/or pharmaceutical companies were contacted for additional information. Study Selection: Two reviewers independently selected randomized clinical trials that compared fixed doses of a second-generation antipsychotic, haloperidol, or fluphenazine for relapse prevention in patients with stable schizophrenia. Data Extraction and Synthesis: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline, all parameters in duplicate were extracted and frequentist dose-response random-effects meta-analyses were conducted. Main Outcomes and Measures: Study-defined relapse (primary outcome), rehospitalization, Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale total score reduction from baseline, all-cause discontinuation, and dropouts due to adverse events. Results: Evidence from 72 dose arms from 26 studies with 4776 participants was analyzed. The efficacy-related dose-response curves had a hyperbolic shape meaning that the probability to relapse decreased rapidly with doses of up to 5-mg/d risperidone equivalent (relative relapse risk, 0.43; 95%...