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.
The focus of this study was to reanalyze previous studies using Bayesian analysis to determine which SSRIs, if any, were associated with different types of birth defects.
The study took place across 10 centers in the U.S., with almost 18,000 mothers of infants who did not experience birth defects and almost 10,000 mothers of infants who did experience birth defects. The study then looked to see if these mothers had used citalopram, escitalopram, fluoxetine, paroxetine, or sertraline in the month before pregnancy through the third month of pregnancy. The study was adjusted to take into accound race/ethnicity, education level, smoking, and obesity of the mother.
The study concluded that the most commonly used SSRI was sertraline, but no birth defects could be correlated to the use of this drug. There were also no defects strongly correlated with citalopram or escitalopram. The researchers concluded that some birth defects did occur 2-3.5 times more frequently in the infants of women using paroxetine or fluoxetine early in pregnancy.
This study is interesting to me, as it gives us a better guideline of which SSRIs are safer to use in pregnant women. If the switch from one type of SSRI can dramatically reduce the risk of birth defect, I think most mothers would be happy to know this and would be very likely to switch medications.
Link to Article
Although pain is not listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM) as a symptom of major depressive disorder (MDD), previous studies have shown that a large proportion of patients with depressive report symptoms of pain. In addition, research has shown that pain and depression may share common pathways in the body. They may be connected through stress and the hypothalamic-pituitary-adrenal axis.
This study aimed to see how baseline levels of pain affect outcomes in patients treated for MDD with fluoxetine. Specifically, the study hypothesized that severity of baseline would be associated with poorer outcomes and a distinct clinical profile. For 6 weeks in an in-patient hospital, 119 MDD patients were given 20 mg fluoxetine daily doses and monitored for various outcomes. Outcomes included adherence, pain severity and pain interference (measured by the body pain index of the Medical Outcomes Study Short-Form), symptom severity (measured by the Hamilton Rating Scale for Depression), social functioning (measured by the Work and Social Adjustment Scale), and adverse event severity (Utvalg for Kliniske Undersogelser Side Effect Rating Scale).
Results from this study showed that pain and multiple aspects of MDD were associated and that patients with higher baseline levels of pain experienced more severe depressive symptoms. Specifically, subjects with higher levels of pain had greater risk of suicide and stressful life events. They also had less improvement in depressive symptoms despite receiving the same fluoxetine treatment as well as more functional impairment.
This study reminds me of the pain lecture from Dr. Pruskowski as she also explained the connection between depression and pain. Being cognizant of this connection can help us better understand our patients as pharmacists. Perhaps we can inquire about MDD patients’ pain levels during medication therapy management. I would be curious to see if there is evidence supporting the use of pain treatments to help improve depressive symptoms in those with both severe pain and depression. If so, many patients may have a drug therapy problem of needing additional therapy.
Lin H, Wang F, Lin C. Pain affects clinical patterns and treatment outcomes for patients with major depressive disorder taking fluoxetine. J Clin Psychopharmacol. 2015; 35(6):661-6