Role of magnesium supplementation in the treatment of depression: A randomized clinical trial

PLoS ONE

Jun 2017

DOI: 10.1371/journal.pone.0180067

Citations:113

Influential Citations:5

Interventional (Human) Studies

Enhanced Details

Methods

Open-label, randomized crossover trial in outpatient primary care clinics; 126 adults (mean age 52; 38% male) with mild-to-moderate depression (PHQ-9 5–19); randomized to immediate vs delayed magnesium treatment for 6 weeks, then cross-over to the other condition.

Intervention

Magnesium chloride taken orally as four 500 mg tablets daily for a total of 248 mg elemental magnesium per day, for 6 weeks.

Results

Magnesium chloride supplementation produced a clinically and statistically meaningful improvement in depressive symptoms (PHQ-9 −6.0 points; 95% CI −7.9 to −4.2; P<0.001) and anxiety symptoms (GAD-7 −4.5 points; 95% CI −6.6 to −2.4; P<0.001) over 6 weeks versus no treatment. Effects appeared within two weeks and persisted during treatment. Adherence averaged about 83%; 61% would use magnesium in the future. Benefits were observed across subgroups (age, gender, baseline severity, baseline magnesium, antidepressant use). Magnesium was generally well tolerated; diarrhea occurred in 8 participants; no major safety concerns. Implication: 248 mg elemental magnesium daily can be a fast, safe, and inexpensive adjunct or alternative to antidepressants for adults with mild-to-moderate depression.

Limitations

No placebo arm and no blinding; potential selection bias from recruitment via primary care; single-center, relatively small sample with limited racial diversity; short duration; lack of serum magnesium measurement; some subgroups small; long-term efficacy unknown.

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. show less