Simvastatin as an Adjuvant Therapy to Fluoxetine in Patients with Moderate to Severe Major Depression

Statins may not just be for dyslipidemia– this study provides evidence that they can be used as an adjuvant therapy with antidepressants. Statins and major depressive disorder (MDD) are not as unrelated as they may seem. Many processes mitigated by statins, like inflammation, oxidative stress, and vascular abnormalities, are involved in major depressive disorder. Statins have also been found to have effects on other neurological disorders, such as Alzheimer’s Disease and Multiple Sclerosis. Animal studies have shown that statins inhibit NMDA, which could potentially be therapeutic for those with depression.

This study examined the effects of simvastatin therapy (20 mg daily and later 40 mg daily) along with fluoxetine for those with MDD. Adherence, Hamilton Depression Rating Scale, and adverse events were assessed. Those in the simvastatin/fluoxetine group had significantly improved depressive symptoms than the placebo group receiving fluoxetine alone, and they even showed significant improvement early in the trial. It should be noted, however, that this study was short (6 weeks) and small in sample size.

Previous studies showed mixed/ inconclusive evidence for the efficacy of statins in improving depressive symptoms, but this study added to the evidence supporting adjuvant therapy with statins for MDD. Any step in the direction of improving symptoms for those with depressive is a positive step as current antidepressants are not effective in about 30% of patients. The mechanism of how statins can affect depression is not completely understood, but it likely involves NMDA receptors, glutamate uptake, and protecting neurons from glutamate-induced cell death. Some of these statin effects may be independent of the HMG-CoA enzyme inhibition action of the medication.

Does this seem like a promising approach to treating depression? How would patients react to taking an extra medication and possibly enduring some adverse effects, such as muscle pain, for a small improvement in depressive symptoms?

Gougol A, Zareh-Mohammadi N, Raheb S, et al. Simvastatin as an adjuvant therapy to fluoxetine in patients with moderate to severe major depression: A double-blind placebo-controlled trial. Psychopharmacol. 2015; 29:575-81.