Obesity and major depressive disorder (MDD) are two prevalent worldwide health conditions associated with high morbidity and mortality. The evidence shows the bidirectional relationship between them, likely due to overlapping biological mechanisms. Statins, commonly prescribed as lipid-lowering agents, have also been studied for their potential antidepressant properties in both animal models and small-scale human studies due to their anti-inflammatory and neuroprotective effects.
This study aimed to investigate the efficacy of simvastatin combined with escitalopram in reducing depressive symptoms compared to a placebo in adults with MDD and obesity. This study was conducted on adults with MDD and obesity from nine German tertiary care centres from August 2020 to June 2024.
In a double-blind, randomized controlled trial, a total of 161 adult patients with MDD aged 18 to 65 years, along with a body mass index (BMI) of at least 30, were included. Participants received 10 mg of escitalopram for the first two weeks, followed by 20 mg for the remaining duration of the 12-week trial. This was combined with either 40 mg of simvastatin or a placebo daily.
The primary outcome was the change in depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) ratings in the intention-to-treat (ITT) population. Results showed no significant difference in MADRS scores between the simvastatin and placebo groups with a 95% confidence interval CI, −2.08 to 3.02, and P = 0.71. A total of 123 participants reported adverse events (AEs), and the rates were comparable between both groups. Three serious adverse events (SAEs) occurred in one participant who became unintentionally pregnant and underwent an abortion shortly afterward.
The federal regulatory body and the ethical commission of the federal state of Berlin examined and authorized the trial and protocol. This study did not collect participants’ race or ethnicity data because it is strictly restricted by German data protection regulations. An independent central pharmacy used a computer-generated randomized process to assure concealed allocation.
With the help of the permuted block approach, participants were divided by study site and randomly assigned to either simvastatin or a placebo in a 1:1 ratio. Escitalopram dosage could be adjusted based on tolerability: increased after two weeks or reduced if adverse effects occurred at 20 mg. All randomized patients with at least one post-baseline MADRS score were included in the ITT analysis. P-values and 95% confidence intervals were reported to test the null hypothesis of no treatment effect.
In patients with MDD and obesity, the result of this randomized controlled trial shows that simvastatin did not have any extra antidepressant effects when combined with escitalopram. While statins should continue to be used according to current guidelines for primary and secondary cardiovascular disease prevention, their use as adjunctive treatment for depression in this population is not supported by this trial. Nonetheless, the study confirmed that simvastatin favourably impacts lipid and inflammatory profiles. Consistent with broader meta-analysis findings, this trial also highlights that smaller studies often report greater effect sizes than larger trials.
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. Published online June 4, 2025. doi:10.1001/jamapsychiatry.2025.0801
