What is the clinical evidence from this study?

Study design: Systematic Review. Population: Miscellaneous conditions, dementia, or psychiatric conditions. Intervention: Antipsychotics vs. No antipsychotic exposure. Primary outcome: Pneumonia (OR 1.84, 95% CI 1.62-2.09).

What does this research mean for the field?

Antipsychotic exposure is most strongly associated with an increased risk of pneumonia, followed by hip fracture and venous thromboembolism, whereas associations with stroke, sudden cardiac death, and myocardial infarction are weaker. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

July 2, 2019Open Access

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

Key Result

Antipsychotic exposure was most strongly associated with an increased risk of pneumonia (OR 1.84), followed by hip fracture (OR 1.57) and venous thromboembolism (OR 1.55).

Study Design

Type

Systematic Review

Structured PICO

Does antipsychotic exposure increase the risk of life-threatening medical events (hip fracture, thromboembolism, stroke, myocardial infarction, pneumonia, sudden cardiac death) in patients with psychiatric or medical conditions?

Population

Participants in 68 observational studies from 6 systematic reviews. Populations included miscellaneous conditions (69.1%), dementia (14.7%), or psychiatric conditions (16.2%). Mean age 55.7 ± 6 years, 58.2% female.

Intervention

Antipsychotic exposure (current use of any antipsychotic drug, ATC/DDD Index N05A, no restriction on dosage or route)

Comparator

Non-exposed subjects

Outcome

Risk of hip fracture, venous thromboembolism, stroke, myocardial infarction, pneumonia, and sudden cardiac deathsafety

Antipsychotic use is associated with an increased risk of several life-threatening medical events, most robustly pneumonia, hip fracture, and venous thromboembolism, highlighting the need for careful risk-benefit assessment.

Main Result

Effect estimate: OR 1.84 (95% CI 1.62-2.09)

Limitations

Considering the observational nature of the primary studies, confounding by indication may have inflated the risk estimates
Significant heterogeneity in terms of populations included in the primary studies
Unable to re-analyse the data by antipsychotic class or by individual drug, as this information was seldom reported

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 and PsycINFO from inception until 30/07/2018 for systematic reviews of observational studies. AMSTAR-2 was used for the 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 ± 12.3 years, 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 ± 12.5 years), 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 ± 3.2 years). 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 ± 13.8 years), 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 ± 6.2 years) 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 ± 9.3 years). 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.

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