Adjunctive simvastatin has no significant benefit for treatment‐resistant depression
The Brown University Psychopharmacology Update · 2023
Evidence of the presence of metabolic dysfunction in some individuals with depression has led to interest in the potential use of statins as repurposed treatments for depression. Some randomized controlled trials have investigated statins as an adjunctive treatment, but they have been limited by small sample sizes. A new 12-week trial evaluated the efficacy and tolerability of simvastatin as an adjunctive treatment to standard care in patients with treatment-resistant depression. The study, conducted at outpatient psychiatric clinics in Pakistan between March 1, 2019, and Feb. 28, 2021, recruited adults aged 18 to 75 with major depressive disorder and at least two failed trials of an antidepressant lasting at least 6 weeks. Individuals with a primary psychotic or bipolar disorder and those currently taking a statin were among those excluded. Participants were randomized to simvastatin 20 mg/day or placebo, with all participants continuing to take a stable dose of their current antidepressant during the trial. The primary outcome was change in depression score from baseline to week 12 on the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included response and remission rates and changes in measures of anxiety. A number of metabolic measures also were assessed. A total of 150 participants were randomized to treatment; the median duration of their current depressive episode was 5 months. There was no significant between-group difference in change in MADRS score at 12 weeks. Results were similar for secondary outcomes, with response and remission rates of 38% and 23%, respectively, in the simvastatin group and 38% and 22%, respectively, in the placebo group. No serious adverse events were reported. “Further research is needed to identify immune-metabolic phenotypes of depression that may be more responsive to, or preventable with, targeted statins or other immunomodulatory treatments,” the study's authors wrote. [Husain, M., et al. (2023). JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2023.0147]