Review Examines Metabolic, Cardiovascular Side Effects of Second-Generation Antipsychotics

Prescription bottles and pills on a counter.
A systematic review examined the metabolic and cardiovascular adverse effects in commonly prescribed second-generation antipsychotics.

A recent meta-analysis provided insight on variations in metabolic and cardiovascular side effect profiles of oral second-generation antipsychotics.

Patients with schizophrenia have almost twice the risk of diabetes and metabolic syndrome as compared to the general population, are at increased risk for cardiovascular disease, and are predisposed to developing comorbidities (diabetes, hypertension, obesity, and metabolic syndrome). First-line antipsychotic therapy used to treat schizophrenia may contribute to the development of metabolic abnormalities and weight gain. A systematic review examined the metabolic and cardiovascular adverse effects of commonly prescribed second-generation antipsychotics.

The meta-analysis included a total of 79 published articles (N=37,467); 61% of the papers were randomized controlled trials (RCTs) and 39% were observational studies. Studies were included if they were published in English and conducted in participants 18 years of age and older in the last 10 years. The literature review included 19 studies on lurasidone, 20 studies on aripiprazole, 49 studies on olanzapine, 6 studies on paliperidone extended release (XR), 13 studies on quetiapine XR, and 27 studies on risperidone

Results showed that patients who took olanzapine and risperidone reported the greatest weight gain (4.52kg and 4.19kg, respectively). Olanzapine was also associated with the largest body mass index (BMI) increase (1.59kg/m2) and significantly increased triglycerides by 33.10mg/dL and fasting glucose by 6.24mg/dL.

Paliperidone treatment was reported to increase total cholesterol (14.69mg/dL), but also led to an increase in HDL cholesterol (0.57mg/dL). Aripiprazole also showed a large increase in triglyceride level (18.63mg/dL).

The highest increase in systolic and diastolic blood pressure was reported with quetiapine XR (2.60 and 2.77 mmHg, respectively). Treatment with this agent also led to the greatest decrease in fasting glucose (-0.59mg/dL).

Conversely, lurasidone was associated with the lowest increase in body weight (0.43kg), a reduction in BMI (-0.10kg/m2), and a decrease in total cholesterol (-8.01mg/dL) and triglycerides (-5.33mg/dL). However, it resulted in the highest decrease in HDL cholesterol (-2.05mg/dL).

The literature review included studies from various countries, which increased generalizability. The study presented some limitations due to variations in doses and follow-up time, and lack of double-blinding in some RCTs. The authors were unable to evaluate the impact of the metabolic adverse effects on quality of life.

Despite the limitations, the results of the meta-analysis were consistent with previous studies and showed variations in metabolic and cardiovascular side effects across second-generation antipsychotics. The authors concluded that in addition to clinical applications, this literature review could be used to perform cost-effectiveness and budget impact analyses for future health economic studies.


Rognoni C, Bertolani A, Jommi C. Second-generation antipsychotic drugs for patients with achizophrenia: Systematic literature review and meta-analysis of metabolic and cardiovascular side effects. Clinical Drug Investigation (2021).

This article originally appeared on MPR