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.

High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery

Atorvastatin is a commonly prescribed medication for hyperlipidemia. It has also been recently found in a study that preoperative statin treatment could decrease the risk of acute kidney injury in patients recovering from cardiac surgery. Acute kidney injury (AKI) affects up to 30% of cardiac surgery patients, and patients who suffer from this complication increase their risk of death by as much as five-fold. This study looked at the efficacy of perioperative statin treatment in prevent AKI occurrences in cardiac surgery patients. The study included cardiac surgery patients who had never received statin treatment before and patients already on statin therapy. The statin-naïve patients were given 40 mg of atorvastatin that morning of and daily after surgery, and patients on statin therapy took regular dosage up to surgery and 80 mg after surgery, or they received a placebo. The study found that perioperative dosing of atorvastatin in patients already on statin did not reduce AKI risk and may even increase AKI risk in statin-naïve patients and in patients with CKD compared to the placebo treatment. These results did not support statin initiation to prevent AKI post-cardiac surgery.

I think it is really interesting to investigate new indications for already well-established medications. In terms of the drug development process, it is much easier and more cost-effective to find new indications for an already approved drug than it is to come up with an entirely new compound. It is also interesting that a previous study had found that statin treatment could possibly decrease the risk of AKI, while this study found that it did not or even could potentially increase the risk of AKI incidence in certain patients. This shows that many different studies’ results must be taken into account before using any of them to support any claims, find proper treatments techniques, or provide patient counseling.

Billings FT, Hendricks PA, Schildcrout JS et al. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery. JAMA. 2016; 315:877-888.

http://jama.jamanetwork.com/article.aspx?articleid=2492851