Antipsychotic drug dosing and study discontinuation in schizophrenia: A systematic review and dose-response meta-analysis

作者：Jing Tian, Spyridon Siafis, Xiao Lin, Hui Wu, Johannes Schneider‐Thoma, Stefan Leucht · 发表于：European Neuropsychopharmacology · 年份：2025 · DOI：10.1016/j.euroneuro.2025.02.012 · 被引用次数：13 · 研究领域：Schizophrenia research and treatment、Healthcare Decision-Making and Restraints、Bipolar Disorder and Treatment

• Antipsychotics differ in their tendency to be associated with treatment discontinuation. • Most dose-response curves of studies discontinuation follow hyperbolic, U-shaped, or monotonic patterns. • Discontinuation due to inefficacy usually mirrors all-cause discontinuation. • The parallel between inefficacy-related and all-cause discontinuation likely reflects that most dropouts in antipsychotic trials result from treatment inefficacy rather than side effects. • Limited data were available for dose-response curves on discontinuation due to side effects, but when assessable, these curves showed a sharp increase with higher doses. High discontinuation rates compromise the effectiveness of treatment regimens for schizophrenia, because consistent medication adherence is essential for the efficacy of antipsychotics. Understanding the relationship between antipsychotic doses and discontinuation rates is important. This study explores this relationship to identify doses that maximize treatment adherence and minimize discontinuation. We systematically searched multiple electronic databases for fixed-dose RCTs assessing 20 antipsychotics in patients with acute exacerbation of schizophrenia and related disorders. We analyzed dose-response relationships using a one-stage dose-response meta-analysis within a frequentist framework, employing restricted cubic splines to model the relationships. The primary outcome was discontinuation for any reason, and secondary outcomes were discontinu...