Academic Journal
Reclassifying dropouts from antipsychotic trials due to study-reported adverse events: a systematic review and individual-participant-data meta-analyses.
| Τίτλος: | Reclassifying dropouts from antipsychotic trials due to study-reported adverse events: a systematic review and individual-participant-data meta-analyses. |
|---|---|
| Συγγραφείς: | Furukawa Y; Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany; German Center for Mental Health (DZPG), partner site Munich-Augsburg, Germany; Department of Neuropsychiatry, University of Tokyo, Tokyo, Japan. Electronic address: yuki.furukawa@tum.de., Siafis S; Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany; German Center for Mental Health (DZPG), partner site Munich-Augsburg, Germany., Schneider-Thoma J; Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany; German Center for Mental Health (DZPG), partner site Munich-Augsburg, Germany., Nomura N; Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany; German Center for Mental Health (DZPG), partner site Munich-Augsburg, Germany; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan., Fares-Otero NE; Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany; Department of Psychiatry and Psychology, Bipolar and Depressive Disorders Unit, Hospital Clínic, Institute of Neurosciences (UBNeuro), University of Barcelona, Fundació Clínic per a la Recerca Biomèdica, Institut investigations Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Barcelona, Catalonia, Spain., Storosum BWC; Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, Location Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands., Zantvoord JB; Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, Location Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands., Schwarz C; BASTA-Bündnis für psychisch erkrankte Menschen, Munich, Germany., Schulz J; BASTA-Bündnis für psychisch erkrankte Menschen, Munich, Germany., Naiser H; BASTA-Bündnis für psychisch erkrankte Menschen, Munich, Germany., Möhrmann KH; Landesverband Bayern der Angehörigen psychisch erkrankter Menschen e.V., Munich, Germany., Priller J; Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany; German Center for Mental Health (DZPG), partner site Munich-Augsburg, Germany; Neuropsychiatry, Charité-Universitätsmedizin Berlin and Deutsches Zentrum Für Neurodegenerative Störungen, 10117, Berlin, Germany; University of Edinburgh and UK DRI, Edinburgh, UK., Davis JM; Psychiatric Institute, University of Illinois at Chicago, Chicago, IL, USA; Johns Hopkins University, Baltimore, MD, USA., Efthimiou O; Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland., Salanti G; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland., Leucht S; Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany; German Center for Mental Health (DZPG), partner site Munich-Augsburg, Germany. |
| Πηγή: | European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology [Eur Neuropsychopharmacol] 2026 Oct; Vol. 111, pp. 112874. Date of Electronic Publication: 2026 May 15. |
| Τύπος έκδοσης: | Journal Article; Systematic Review; Meta-Analysis |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9111390 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7862 (Electronic) Linking ISSN: 0924977X NLM ISO Abbreviation: Eur Neuropsychopharmacol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier, c1990- |
| Ιατρικοί όροι (MeSH): | Antipsychotic Agents*/adverse effects , Antipsychotic Agents*/therapeutic use , Schizophrenia*/drug therapy , Patient Dropouts*/statistics & numerical data , Randomized Controlled Trials as Topic*, Humans ; Male |
| Περίληψη: | In antipsychotic trials for acute schizophrenia, dropout reasons are typically classified into inefficacy, adverse events (AEs), and other reasons. AEs can include not only somatic, but also psychiatric AEs, which may reflect inefficacy. However, studies seldom report them separately. We examined detailed reasons for dropouts attributed to AEs and assessed the impact of reclassification. We searched Vivli for randomized controlled trials with individual-participant-data on adults with acute schizophrenia (up to April 9, 2025). When dropout was attributed to an AE, we cross-checked reports and recategorized the corresponding dropouts into somatic, psychiatric, and other AEs using MedDRA(v28.1). We performed random-effects meta-analyses to compare antipsychotics and placebo for i) the study-reported dropouts due to AEs, and for ii) dropouts reclassified as due to somatic AEs. Seventeen trials (6823 participants; 70% male; mean age 40.9 years; mean Positive and Negative Syndrome Score 93.1) were included. Studies reported that 1369 dropouts due to inefficacy, 445 dropouts due to AEs, and 1173 dropouts due to other reasons. We reclassified the study-reported dropouts due to AEs as due to psychiatric (n = 223), somatic (n = 207), and other AEs (n = 15). We did not find evidence of difference between antipsychotics and placebo with respect to study-defined dropouts due to AEs (OR, 0.93 [95% CI; 0.72, 1.12]). However, we found evidence that dropouts reclassified as somatic AEs were more frequent with antipsychotics (OR, 1.54 [95% CI; 1.04, 2.27]). We conclude that combining somatic with psychiatric AEs may mask the true impact of antipsychotics on tolerability. Future trials should report these categories separately. (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stefan Leucht reports financial support was provided by The German Federal Ministry of Research, Technology and Space. Yuki Furukawa reports a relationship with Panasonic Corporation that includes: consulting or advisory. Yuki Furukawa reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: speaking and lecture fees. Nobuyuki Nomura reports a relationship with Sumitomo Pharma Co Ltd that includes: funding grants. Nobuyuki Nomura reports a relationship with The Federal Ministry of Education and Research that includes: employment. Stefan Leucht reports a relationship with Alkermes that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Apsen that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Eisai that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship withGedeon Richter that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Janssen that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Karuna that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Kynexis that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Lundbeck that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Medichem that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Medscape that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Merck Shar and Dohme that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Mitsubishi that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Neurotorium that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with NovoNordisk that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Orionpharma that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Otsuka that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Recordati that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Roche that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Rovi that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with Sanofi Aventis that includes: consulting or advisory and speaking and lecture fees. Stefan Leucht reports a relationship with TEVA that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Adverse events; Antipsychotics; Schizophrenia; Side effects; Tolerability |
| Substance Nomenclature: | 0 (Antipsychotic Agents) |
| Entry Date(s): | Date Created: 20260515 Date Completed: 20260812 Latest Revision: 20260829 |
| Update Code: | 20260830 |
| DOI: | 10.1016/j.euroneuro.2026.112874 |
| PMID: | 42139983 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-7862 |
|---|---|
| DOI: | 10.1016/j.euroneuro.2026.112874 |