Metabolic effects of long-term Aripiprazole use in patients with schizophrenia and first-episode psychosis: A systematic review

Braz J Psychiatry. 2026 Jul 13. doi: 10.47626/1516-4446-2026-4803. Online ahead of print.

ABSTRACT

OBJECTIVE: Schizophrenia and first-episode psychosis often require long-term antipsychotic treatment, making metabolic adverse effects an important clinical concern. This study evaluated the long-term metabolic effects of aripiprazole compared with other antipsychotics.

METHODS: This systematic review analyzed randomized controlled trials with at least one year of follow-up and was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. The protocol was prospectively registered in PROSPERO (CRD4202563245). Two authors independently conducted a systematic search in MEDLINE/PubMed, Embase, and Cochrane databases from inception to December 2024. Adult patients with schizophrenia spectrum disorders or first-episode psychosis were included. Primary outcomes were weight, body mass index, and cholesterol. Two authors independently assessed the risk of bias in the included randomized clinical trials using the Cochrane Risk of Bias 2 tool, with any discrepancies resolved by a third reviewer.

RESULTS: Long-term aripiprazole treatment was associated with comparable metabolic changes, including increases in body weight, BMI, and lipid parameters. However, head-to-head comparisons did not demonstrate a consistent pattern of greater metabolic worsening with aripiprazole relative to other antipsychotics. Some studies reported no statistically significant between-group differences in weight, BMI, or cholesterol, while others described numerically lower frequencies of selected metabolic adverse events with aripiprazole. Nevertheless, statistical testing and reporting of confidence intervals were inconsistent across studies, limiting firm comparative conclusions.

CONCLUSIONS: These findings suggest that aripiprazole may have a comparably favorable metabolic profile for selected outcomes during chronic treatment; however, increases in weight, BMI, and lipid parameters were observed in some studies. Further long-term studies with standardized metabolic outcome reporting are warranted to clarify its comparative effects across broader clinical populations.

PMID:42441918 | DOI:10.47626/1516-4446-2026-4803