Simvastatin fails to provide Added Antidepressant Effect in MDD with Obesity: JAMA

A new study published in the Journal of American Medical Association showed that simvastatin did not provide additional antidepressant benefits when combined with escitalopram in patients with major depressive disorder (MDD) and obesity, although it did improve cardiovascular risk factors.

Obesity and major depressive disorder are prevalent noncommunicable diseases with significant disease burdens that commonly co-occur. Interestingly, a biological connection between obesity, metabolic syndrome, and depression has been proposed by convergent lines of evidence from genetic and observational research as well as animal models.

The antidepressant potential of statins has been suggested by a number of modest randomized clinical studies (RCTs). Thus, to determine if simvastatin added to escitalopram is more effective than a placebo at reducing depressive symptoms, this trial was carried out.

This investigation included adults with MDD and concomitant obesity from nine German tertiary care settings. Analysis of the data took place between July and October of 2024. In addition to escitalopram (10 mg during the first two weeks, then raised to 20 mg until the completion of the research), simvastatin (40 mg daily) or a placebo was administered in a double-blind manner for 12 weeks. The Montgomery-Åsberg Depression Rating Scale (MADRS) score change from baseline (week 0) to week 12 was the main result.

The intention-to-treat analysis comprised 160 of the 161 patients who were recruited at 9 locations in Germany between August 21, 2020, and June 06, 2024 (mean [SD] age, 39.0 [11.0] years; 126 female [79%]; placebo: n = 79, simvastatin: n = 81). Blinding was successfully maintained throughout the experiment, and retention was outstanding (95.6%).

Four severe adverse events occurred, and there was no difference between the groups. Simvastatin addition did not significantly affect MADRS scores in the intention-to-treat population, according to primary endpoint analysis (mixed models for repeated measures least squares mean difference, 0.47 points; 95% CI, -2.08 to 3.02; P =.71).

Simvastatin substantially decreased LDL cholesterol (-40.37 mg/dL), total cholesterol (-39.07 mg/dL), and C-reactive protein (-1.04 mg/L) when compared to a placebo (all P <.01), but it had no effect on secondary outcomes relating to mental health. Overall, the study showed that even while simvastatin improved the cardiovascular risk profile, it had no extra antidepressant benefits when used with escitalopram in individuals who had both obesity and concomitant MDD.

Source:

Otte, C., Chae, W. R., Dogan, D. Y., Piber, D., Roepke, S., Cho, A. B., Trumm, S., Kaczmarczyk, M., Brasanac, J., Wingenfeld, K., Koglin, S., Wieditz, J., Junghanns, K., Lucht, M., Prvulovic, D., Krüger, T. H. C., Terock, J., Haaf, M., Hofmann, T., … Gold, S. M. (2025). Simvastatin as add-on treatment to escitalopram in patients with major depression and obesity: A randomized clinical trial. JAMA Psychiatry (Chicago, Ill.). https://doi.org/10.1001/jamapsychiatry.2025.0801