JAMA Psychiatry

Adding a statin to antidepressant therapy shows no benefit in patients in obesity

June 9, 2025

Simvastatin didn’t confer additional antidepressant benefit when added to escitalopram in patients with major depressive disorder (MDD) and obesity. Clinicians should be cautious in expecting mood-related benefits from statins in this population and continue to rely on established antidepressant strategies.

Study details: This randomized, double-blind, placebo-controlled trial evaluated the efficacy of adjunctive simvastatin (40 mg/day) added to escitalopram in adults with MDD and obesity. A total of 160 participants were randomized to receive either simvastatin or placebo alongside escitalopram therapy over 12 weeks. The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline (week 0) to week 12.

Results: Both groups showed improvement in depressive symptoms over time, but there wasn’t a statistically significant difference between the simvastatin and placebo groups at any time point (mixed models for repeated measures least squares mean difference, 0.47 points; 95% confidence interval, -2.08 to 3.02; P = .71). While depressive symptom reduction was similar between groups (MADRS: -13.97 simvastatin vs -13.50 placebo), simvastatin significantly improved metabolic markers, including LDL cholesterol (-40.37 vs -3.78 mg/dL), total cholesterol (-39.07 vs -4.89 mg/dL), and C-reactive protein (-1.04 vs +0.57 mg/L; all P < 0.01).

Source:

Otte C, et al. (2025, June 4). JAMA Psychiatry. Simvastatin as Add-On Treatment to Escitalopram in Patients With Major Depression and Obesity: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40465256/