Add-On Simvastatin Shows No Benefit in Depression

Medscape

13-06-2025

In a trial of patients with major depressive disorder (MDD) and obesity, adding simvastatin to escitalopram treatment led to no significant reduction in depressive symptoms compared with placebo; however, the combination effectively reduced levels of low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP).
METHODOLOGY:
This confirmatory, double-blind, placebo-controlled trial included 160 adults (mean age, 39 years; 79% women) with MDD and comorbid obesity from nine tertiary care centres in Germany.
Participants were randomly assigned to receive either simvastatin (40 mg/d; n = 81) or placebo (n = 79) as add-on to escitalopram (10 mg for the first 2 weeks, then increased to 20 mg until the end of the study) for 12 weeks.
The primary outcome was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to week 12.
The key secondary outcome was the change in self-reported Beck Depression Inventory II (BDI-II) scores.
TAKEAWAY:
Compared with the use of add-on placebo, the use of add-on simvastatin led to no significant change in MADRS scores ( P = .71) and BDI-II scores ( P = .70).
= .71) and BDI-II scores ( = .70). Moreover, compared with the use of add-on placebo, the use of add-on simvastatin led to a significant reduction in levels of LDL cholesterol ( P < .001), total cholesterol ( P < .001), and CRP ( P = .003).
< .001), total cholesterol ( < .001), and CRP ( = .003). Add-on simvastatin did not affect any mental health-related secondary endpoint, despite improving the cardiovascular risk profile.
Four severe adverse events were reported, with no significant differences observed between the groups.
IN PRACTICE:
"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. Given that both MDD and obesity are associated with increased cardiovascular risk and higher mortality, statins should be prescribed in this comorbid group of patients following the guidelines for statin use in primary prevention," the authors wrote.
SOURCE:
This study was led by Christian Otte, MD, Charité — Universitätsmedizin Berlin, Berlin, Germany. It was published online on June 04 in JAMA Psychiatry .
LIMITATIONS:
This study was conducted in tertiary care centres in a high-income country, with patients showing moderate symptom severity and a high response rate, which limited its generalisability. Additionally, participants with an established indication for statin treatment and those with a history of suicide attempt were not included.
DISCLOSURES:
This study was supported by a grant from the German Ministry of Education and Research and sponsored by Charité — Universitätsmedizin Berlin. Several authors reported receiving grants and personal fees from various sources, outside the submitted work. Details are provided in the original article.