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

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology Pub Date : 2025-03-08 DOI:10.1016/j.euroneuro.2025.02.012

Jing Tian , Spyridon Siafis , Xiao Lin , Hui Wu , Schneider-Thoma Johannes , Leucht Stefan

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引用次数: 0

Abstract

Background

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.

Methods

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 discontinuation due to inefficacy and side effects.

Results

Analysis of 136 trials involving 44,126 participants revealed various dose-response relationships for antipsychotics. For the primary outcome, all-cause discontinuation, amisulpride, cariprazine, olanzapine (Zyprexa), and quetiapine demonstrated U-shaped curves, indicating optimal dosing thresholds where further increases in dosage led to heightened discontinuation rates, possibly due to side effects. Aripiprazole, asenapine, brexpiprazole, clozapine, paliperidone, and risperidone (Risperdal) had plateaus, suggesting no additional benefit from increasing doses beyond specific points. For haloperidol, iloperidone, lumateperone, lurasidone, sertindole, and ziprasidone, the dose-response curves did not reach a plateau within the examined doses. Inefficacy discontinuation curves were similar to total discontinuation. Most discontinuation for side-effects curves showed sharp increases in side-effects associated with higher doses.

Conclusion

Dose discontinuation curves varied between the antipsychotics and included U-shaped, monotonic, and hyperbolic patterns. Future studies should consistently present disease-related and side-effect-related dropouts due to adverse events separately.

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来源期刊

European Neuropsychopharmacology 医学-精神病学

CiteScore

10.30

自引率

5.40%

发文量

730

审稿时长

41 days

期刊介绍： European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.