Metabolic Adverse Effects of Low-Dose Quetiapine: A Systematic Review and Meta-Analysis

The use of off-label, low doses of second-generation antipsychotics (SGAs), in particular quetiapine, has risen significantly. SGAs are known to cause metabolic adverse effects, including weight gain. The aim of this systematic review and meta-analysis was to assess the impact of low-dose quetiapine on metabolic outcomes, such as weight, glycemic, and lipid metabolism.

Following the PRISMA statement, PubMed, Web of Science Core Collection, Cochrane Library, ClinicalTrials.gov, Google Scholar, and PsycINFO were systematically searched for randomized controlled trials > 4 weeks, reporting metabolic outcomes of quetiapine < 200 mg. RoB2 was used to assess bias. SPSS was used for quantitative data management and aggregation.

Eight unique studies (n = 3085) were included, six of which were included in the meta-analysis. Low doses of quetiapine led to significant weight gain (mean difference [MD] = 0.58 kg, 95% CI: 0.32-0.83) and HDL cholesterol reduction (MD = -1.25 mg/dL, 95% CI: -1.86 to -0.65). Patients gaining ≥ 7% of baseline weight was 2.12 times more likely to have taken quetiapine.

Despite limited generalizability, these findings suggest that, even at low doses, quetiapine has an impact on metabolism. Further research is needed to clarify its role in metabolic dysregulation. This study was registered in the international database of prospectively registered systematic reviews (PROSPERO CRD420250588527).