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Antipsychotic use and risk of life-threatening medical events: umbrella review of observational studies

Research output: Contribution to journalReview article

Davide Papola, Giovanni Ostuzzi, Chiara Gastaldon, Gian Paolo Morgano, Elena Dragioti, Andre F. Carvalho, Paolo Fusar-Poli, Christoph U. Correll, Marco Solmi, Corrado Barbui

Original languageEnglish
Pages (from-to)227-243
Number of pages17
JournalActa Psychiatrica Scandinavica
Issue number3
Early online date2 Jul 2019
Accepted/In press1 Jul 2019
E-pub ahead of print2 Jul 2019

Bibliographical note

doi: 10.1111/acps.13066


King's Authors


Abstract Objective To quantify the risk of hip fracture, thromboembolism, stroke, myocardial infarction,pneumonia, and sudden cardiac death associated with exposure to antipsychotics. Methods Systematic searches were conducted in Medline, Embase, PsychINFO from inception until 30/07/2018 for systematic reviews of observational studies. AMSTAR-2 was used for quality assessment of systematic reviews, while the strength of associations was measured using GRADE and quantitative umbrella review criteria(URC). Results Sixty-eight observational studies from six systematic reviews were included. The association between antipsychotic exposure and pneumonia was the strongest (URC=class I; GRADE=low quality; odds ratio [OR]=1.84, 95% confidence interval [CI]=1.62-2.09; participants=28,726; age=76.2±12.3years), followed by the association with hip fracture (URC=class II; GRADE=low quality; OR=1.57,95%CI=1.42-1.74; participants=5,288,118; age=55.4±12.5years), and thromboembolism (URC=class II; GRADE=very low quality; OR=1.55,95%CI=1.31-1.83; participants=31,417,175; age=55.5±3.2years). The association was weak for stroke (URC=class III; GRADE=very low quality; OR=1.45,95%CI=1.24-1.70; participants=65,700; age=68.7±13.8years), sudden cardiac death (URC=class III; GRADE=very low quality; OR=2.24,95%CI=1.45-3.46; participants=77,488; age=52.2±6.2years), and myocardial infarction (URC=class III; GRADE=very low quality; OR=2.21,95%CI=1.41-3.46; participants=399,868; age=74.1±9.3years). Conclusion The most robust results were found for the risk of pneumonia, followed by the risk of hip fracture and thromboembolism. For stroke, sudden cardiac death, and myocardial infarction the strength of association was weak. The observational nature of the primary studies may represent a source of bias. This article is protected by copyright. All rights reserved.

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