Add-On Simvastatin Not Effective as Antidepressant in Patients With MDD and Obesity

Maria Mantas
09/02/2025

When added to escitalopram, simvastatin improved the cardiovascular risk profile but did not offer additional antidepressive effects in patients with comorbid major depressive disorder (MDD) and obesity, according to study results published in JAMA Psychiatry. 

“MDD and obesity frequently co-occur, and the presence of one condition increases the risk for developing the other by approximately 50% to 60%,” wrote Christian Otte, MD, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Department of Psychiatry and Psychotherapy, Humboldt-Universität zu Berlin, Berlin, Germany, and study coauthors. “Thus, evidence-based guidance for better treatment approaches to comorbid depression and obesity is urgently needed.”

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The randomized control trial (RCT) included 161 participants aged 18-65 with Montgomery-Åsberg Depression Rating Scale (MADRS) scores of 18 or greater and body mass index (BMI) of 30 or greater. Participants were assigned to receive either 40 mg of simvastatin daily (n=82) or placebo (n=79) as add-on to escitalopram (10 mg for 2 weeks, then 20 mg until the end of study) for 12 weeks. The researchers then assessed the change in MADRS score at the end of the 12-week period.

Researchers found no significant treatment effect on MADRS scores due to the add-on simvastatin (mixed models for repeated measures least squares mean difference, 0.47 points; 95% CI, −2.08 to 3.02; P = .71). Several secondary outcomes, including self-reported Beck Depression Inventory II (BDI-II) scores, response rates, and remission rates, were also not significantly impacted by the intervention. 

“Even though simvastatin did not exert additional antidepressive effects in our study, it had the expected and well-known effects on lipids and inflammatory activity,” the authors noted. “Clinicians should not be discouraged by the lack of additional antidepressive statins effects in our study but should continue prescribing lipid lowering medications to reduce cardiovascular risk in these patients.”

Reference
Otte C, Chae WR, Dogan DY, et al. Simvastatin as add-on treatment to escitalopram in patients with major depression and obesity: a randomized clinical trial. JAMA Psychiatry. 2025;82(8):759–767. doi:10.1001/jamapsychiatry.2025.0801