Efficacy and tolerability of antipsychotic polypharmacy for schizophrenia spectrum disorders. A systematic review and meta-analysis of individual patient data
- PMID: 39142215
- DOI: 10.1016/j.schres.2024.07.035
Efficacy and tolerability of antipsychotic polypharmacy for schizophrenia spectrum disorders. A systematic review and meta-analysis of individual patient data
Abstract
Background: Antipsychotic polypharmacy (APP) is frequently prescribed for schizophrenia-spectrum disorders. Despite the inconsistent findings on efficacy, APP may be beneficial for subgroups of psychotic patients. This meta-analysis of individual patient data investigated moderators of efficacy and tolerability of APP in adult patients with schizophrenia-spectrum disorders.
Design: We searched PubMed, EMBASE, and the Cochrane Central Register of Randomized Trials until September 1, 2022, for randomized controlled trials comparing APP with antipsychotic monotherapy. We estimated the effects with a one-stage approach for patient-level moderators and a two-stage approach for study-level moderators, using (generalized) linear mixed-effects models. Primary outcome was treatment response, defined as a reduction of 25 % or more in the Positive and Negative Syndrome Scale (PANSS) score. Secondary outcomes were study discontinuation, and changes from baseline on the PANSS total score, its positive and negative symptom subscale scores, the Clinical Global Impressions Scale (CGI), and adverse effects.
Results: We obtained individual patient data from 10 studies (602 patients; 31 % of all possible patients) and included 599 patients in our analysis. A higher baseline PANSS total score increased the chance of a response to APP (OR = 1.41, 95 % CI 1.02; 1.94, p = 0.037 per 10-point increase in baseline PANSS total), mainly driven by baseline positive symptoms. The same applied to changes on the PANSS positive symptom subscale and the CGI severity scale. Extrapyramidal side effects increased significantly where first and second-generation antipsychotics were co-prescribed. Study discontinuation was comparable between both treatment arms.
Conclusions: APP was effective in severely psychotic patients with high baseline PANSS total scores and predominantly positive symptoms. This effect must be weighed against potential adverse effects.
Keywords: Antipsychotic polypharmacy; Effect moderators; Efficacy; Tolerability.
Copyright © 2024 Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest Dr. Anıl Yağcıoğlu has served as a speaker/advisory board member for Janssen, Abdi İbrahim Otsuka, Boehringer Ingelheim, Santa Farma, Nobel and has been an investigator for Janssen, Boehringer Ingelheim. Dr. Kasper served in the past 3 years as a consultant or on advisory boards for Angelini, Biogen, Boehringer, Esai, Janssen, IQVIA, Mylan, Recordati, Rovi, Sage and Schwabe; and he has served on speakers bureaus for Angelini, Aspen Farmaceutica S.A., Biogen, Janssen, Recordati, Schwabe, Servier, Sothema, and Sun Pharma. Dr. R.E. Nielsen has received funding for research or has been an investigator for H. Lundbeck, Otsuka Pharmaceuticals, Compass, Boehringer Ingelheim and Janssen-Cilag. Furthermore, REN has received speakers fee from Bristol-Meyers Squibb, Astra Zeneca, Janssen-Cilag, Lundbeck, Servier, Otsuka Pharmaceuticals, Teva and Eli Lilly. Dr. Remington has received research support from the Canadian Institutes of Health Research (CIHR), University of Toronto, and HLS Therapeutics Inc. Dr. Schmidt-Kaepelin is patent holder of patent No.: 102020106962, and has received speakers honoraria by Boehringer Ingelheim. Dr. Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Tolmar, Vertex, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Mindpax, and Quantic. Lochmann van Bennekom, IntHout, Gijsman, Akdede, Barnes, Galling, Gueorguieva, Kreinin, J. Nielsen, Repo-Tiihonen, Shafti, Xiao and Verkes reported no conflicts of interest.
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