Simvastatin confers no additional antidepressant benefit when added to escitalopram

12 Jun 2025
Simvastatin confers no additional antidepressant benefit when added to escitalopram

In patients with comorbid major depressive disorder (MDD) and obesity, adding simvastatin to escitalopram does not appear to produce additional antidepressive effects despite improving the cardiovascular risk profile, according to a study.

For the study, patients with MDD and comorbid obesity were randomly assigned to receive treatment with simvastatin 40 mg per day or placebo as add-on to escitalopram (10 mg for the first 2 weeks, then increased to 20 mg until the end of study) for 12 weeks. Researchers assessed the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12 as the primary endpoint.

A total of 160 patients were included in the intention-to-treat analysis, including 81 in the simvastatin group and 79 in the placebo group (mean age 39.0 years; 79 percent female). At week 12, the MADRS scores did not significantly differ between the simvastatin and placebo groups (mean difference, 0.47 points, 95 percent confidence interval [CI], −2.08 to 3.02; p=0.71). Likewise, simvastatin did not produce any improvements in any of the mental health–related secondary endpoints relative to placebo.

However, compared with placebo, simvastatin was associated with significantly greater reductions in low-density lipoprotein cholesterol (−40.37 vs −3.78 mg/dL; p<0.001), total cholesterol (−39.07 vs −4.89 mg/dL; p<0.001), and C-reactive protein (−1.04 vs 0.57 mg/L; p=0.003).

There were four cases of serious adverse events, with no difference between the two groups.

Overall, blinding was effectively maintained, and the retention rate was 95.6 percent.

JAMA Psychiatry 2025;doi:10.1001/jamapsychiatry.2025.0801