Long-term metabolic and cardiovascular effects of antipsychotic drugs. A meta-analysis of randomized controlled trials
Abstract
Most of the randomized controlled trials (RCTs) on antipsychotics (APs) have efficacy as their primary endpoint, leading to a lack of evidence on long-term metabolic effects of APs. The aim of the present meta-analysis is to compare different APs for the long-term modification of risk of major adverse cardiovascular events (MACE) and related mortality, in patients with schizophrenia and bipolar disorder. All RCTs found on Medline/Embase of at least 52 weeks up to 19 December 2017, enrolling patients with bipolar disorder or schizophrenia and comparing an AP with another AP or placebo were included. The primary outcome of this analysis was the association of APs with the incidence of cardiovascular death, myocardial infarction (MI), and stroke. 3013 studies were screened, 92 met the selection criteria. MI, stroke and cardiovascular death were reported in 11, 6 and 24 studies, respectively. No significant difference was observed with respect to MI and Stroke; a significantly higher cardiovascular mortality was observed for sertindole when compared to risperidone (Mantel-Haenszel Odds Ratio: 2.56, 95% CI: 1.33 - 5). Long-term cardiovascular effects of APs deserve to be studied more extensively. The request by regulatory authorities of cardiovascular safety data from specifically designed trials would be useful.
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Profound metabolic side effects, including weight gain, increased chance of diabetes, hyperlipidemia, and high blood pressure, are also common with risperidone and aripiprazole.
“Profound metabolic side effects, including weight gain, increased chance of diabetes, hyperlipidemia, and high blood pressure, are also common with risperidone and aripiprazole [139–141].”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [139]
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Cardiovascular disease in patients with severe mental illness
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“Profound metabolic side effects, including weight gain, increased chance of diabetes, hyperlipidemia, and high blood pressure, are also common with risperidone and aripiprazole [139–141].”
Rivas, J., Miranda, C., Restrepo, A., Hernández, M., Erazo, J. M., Martínez, M. J., Lasso, J., López, L., & Gómez-Mesa, J. E. (2025) · Actas Españolas de Psiquiatría · doi:10.62641/aep.v53i4.1904 · Cited by 2 · see citing works
- Authors
- Rotella, F., Cassioli, E., Calderani, E., Lazzeretti, L., Ragghianti, B., Ricca, V., & Mannucci, E.
- Affiliations
- Azienda Ospedaliero-Universitaria Careggi (IT)
- University of Florence (IT)
- Corresponding author
- Rotella, Francesco
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 32
- Pages
- 56-65
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W3000671034
- Cited by
- 48
- References
- 6
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 9 · 2023: 7 · 2022: 5 · 2021: 4 · 2020: 4
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- Otsuka Pharmaceutical
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- antipsychotic drugs, major adverse cardiovascular events, cardiovascular mortality, myocardial infarction, stroke, schizophrenia, bipolar disorder, sertindole, risperidone, metabolic effects, cardiovascular safety
- MeSH terms
- Bipolar Disorder, Cardiovascular Diseases, Humans, Metabolic Diseases, Schizophrenia, Time Factors, Antipsychotic Agents, Randomized Controlled Trials as Topic
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