Statin Disappoints for Treatment-Resistant Depression

Adding simvastatin to standard therapy offers no benefit over placebo for patients with treatment-resistant depression (TRD), new research shows.

The randomized clinical trial findings contradict earlier, smaller studies in patients with major depressive disorder (MDD) that suggested statins may reduce symptoms.

“Given the promising results from preliminary trials of statins in MDD, I was surprised that simvastatin did not separate from placebo in our trial,” lead author M. Ishrat Husain, MBBS, MD, associate professor of psychiatry and scientific head of the Centre for Addiction and Mental Health Clinical Trials Unit at the University of Toronto, Canada, told Medscape Medical News.

“I believe that our findings suggest that statins are not effective augmentation strategies in treatment resistant depression,” Husain said.

The findings were published online February 20 in JAMA Network Open.

Disappointing Results

The double-blind, placebo-controlled randomized clinical trial was conducted in five centers in Pakistan and included 150 patients with major depressive episode whose symptoms did not improve after treatment with at least two antidepressants.

In addition to their prescribed antidepressants, participants received 20 mg/day of simvastatin (n = 77) or placebo (n = 73).

At 12 weeks, both groups reported improvements in Montgomery-Åsberg Depression Rating Scale total scores, but there was no significant difference between groups. The estimated mean difference for simvastatin vs placebo was −0.61 (P = .7).

Researchers found similar results when they compared scores from the Generalized Anxiety Disorder Scale and Morisky Medication Adherence Scale.

“Much like several other studies in mood disorders, our study results were impacted by a large placebo response,” Husain said.

The lack of inclusion of any participants under the age of 18 and the single-country cohort were limitations of the trial. Although it is possible that could have affected the outcome, Husain said it isn’t likely.

It is also unlikely that a different statin would yield different results, he added.

“Simvastatin was selected as it is believed to be most brain penetrant of the statins given its lipophilicity,” Husain said. “Clinical trials of other statins in major depressive disorder in other settings and populations have also been congruent with our results.”

The study was funded by NIHR Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. Husain reports having received grants from Compass Pathways, holds stock options in Mindset, and previously served on the Board of Trustees of the Pakistan Institute of Living and Learning. Disclosures for the other investigators are fully listed in the original article.

JAMA Netw Open. Published online February 20, 2023. Full text

Kelli Whitlock Burton is a reporter for Medscape Medical News covering psychiatry and neurology.

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