Despite Risks, Antipsychotic Polypharmacy on the Rise

TOPLINE:
Global antipsychotic polypharmacy use increased significantly from 1970 to 2023, with 25% of antipsychotic users receiving multiple prescriptions, new research shows. Antipsychotic polypharmacy was associated with higher relapse rates, worse functioning, and greater all-cause mortality risk than monotherapy.
METHODOLOGY:
Researchers analyzed 517 studies published between 1970 and 2023, including 599 individual timepoints.
More than 4 million participants (mean age, 40 years) were included.
The analysis included studies reporting the prevalence of antipsychotic polypharmacy in populations with mental disorders or antipsychotic use, regardless of age or diagnosis; 52% of the studies included patients with schizophrenia spectrum disorders (SSDs).
A random-effects meta-analysis was used to estimate the pooled prevalence of antipsychotic polypharmacy.
TAKEAWAY:
Antipsychotic polypharmacy was observed in 25% of the participants, with rates ranging from 5% in those with dementia to 33% in those with SSDs.
Antipsychotic polypharmacy increased significantly during the study period (P = .0002), with prevalence varying significantly by region, ranging from 15% in North America to 39% in Africa.
The prevalence was also significantly higher in adults than in children and adolescents (27% vs 7%; P < .0001) and among inpatients vs outpatients (31% vs 20%; P < .0001).
Antipsychotic polypharmacy was associated with a higher risk for relapse (relative risk [RR], 1.42; P = .028), psychiatric hospitalization (RR, 1.24; P < .0001), and all-cause mortality (RR, 1.19; P = .047); worse global functioning (standardized mean difference [SMD], −0.31; P <.0001); higher side-effect scores (SMD, 0.33; P < .0001); and a longer corrected QT interval (RR, 0.24; P < .0001) than monotherapy.
IN PRACTICE:
“On the basis of the current evidence regarding the harms and benefits of antipsychotic polypharmacy, this treatment strategy should remain reserved for patients with treatment-resistant schizophrenia who have had insufficient response to monotherapy with clozapine or who are intolerant of or ineligible for treatment with clozapine,” the investigators wrote.
SOURCE:
The study was led by Mikkel Højlund, MD, PhD, Department of Psychiatry Aabenraa, Mental Health Services in the Region of Southern Denmark, Aabenraa, Denmark. It was published online on November 12 in The Lancet Psychiatry.
LIMITATIONS:
High heterogeneity was observed in antipsychotic polypharmacy estimates due to differences in patient characteristics and clinical settings. In addition, limited data from nationwide registers, underrepresentation of individuals with non-SSDs, and insufficient reporting of key variables restricted subgroup analyses and precise estimates for certain regions and decades. Small sample sizes, the lack of severity adjustments, and the absence of input from individuals with lived experience further constrained the findings.
DISCLOSURES:
The study did not receive any external funding. Several authors reported receiving honoraria, consultancy fees, or research support from or holding stock options of various pharmaceutical and healthcare companies, which are fully listed in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 
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