Abstract
Current treatment options for depression are limited by efficacy, cost, availability, side effects, and acceptability to patients. Several studies have looked at the association between magnesium and depression, yet its role in symptom management is unclear. The objective of this trial was to test whether supplementation with over-the-counter magnesium chloride improves symptoms of depression. An open-label, blocked, randomized, cross-over trial was carried out in outpatient primary care clinics on 126 adults (mean age 52; 38% male) diagnosed with and currently experiencing mild-to-moderate symptoms with Patient Health Questionnaire-9 (PHQ-9) scores of 5–19. The intervention was 6 weeks of active treatment (248 mg of elemental magnesium per day) compared to 6 weeks of control (no treatment). Assessments of depression symptoms were completed at bi-weekly phone calls. The primary outcome was the net difference in the change in depression symptoms from baseline to the end of each treatment period. Secondary outcomes included changes in anxiety symptoms as well as adherence to the supplement regimen, appearance of adverse effects, and intention to use magnesium supplements in the future. Between June 2015 and May 2016, 112 participants provided analyzable data. Consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in PHQ-9 scores of -6.0 points (CI -7.9, -4.2; P<0.001) and net improvement in Generalized Anxiety Disorders-7 scores of -4.5 points (CI -6.6, -2.4; P<0.001). Average adherence was 83% by pill count. The supplements were well tolerated and 61% of participants reported they would use magnesium in the future. Similar effects were observed regardless of age, gender, baseline severity of depression, baseline magnesium level, or use of antidepressant treatments. Effects were observed within two weeks. Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity.
Highlights
Depression affects 350 million people worldwide and is predicted to be the leading cause of disease burden by 2030, based on disability-adjusted-life-year [1]
One trial found magnesium chloride to be effective for depression in seniors with type 2 diabetes [10] while another trial found magnesium citrate decreased depression in patients with fibromyalgia [11]
Participants were recruited through primary care providers (PCPs) within a single academic medical center and randomized to begin MgCl2 supplementation immediately or at week 7
Summary
Depression affects 350 million people worldwide and is predicted to be the leading cause of disease burden by 2030, based on disability-adjusted-life-year [1]. Initial antidepressant trials of adequate dose and duration result in only about 50% of patients achieving remission [2]. Even after the addition of other treatments, 20% still suffer from symptoms after 2 years. Nonpharmacologic approaches such as Cognitive Behavioral Therapy and lifestyle interventions require highly trained therapists and several weeks to months to achieve effectiveness [3]. The association between magnesium intake and depression is well documented [4,5,6,7]. Improvement in depression with magnesium supplementation has been reported inconsistently [8, 9], few clinical trials exist. One negative trial used magnesium oxide [12], known to be poorly absorbed
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