Advisor(s): Benjamin Littenberg
Role of Magnesium in the Treatment of Depression: A Randomized Clinical Trial
Background 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.
Methods This was an open-label, blocked, randomized, cross-over trial in outpatient primary care clinics (clinicaltrials.gov Identifier: 02466087). 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 during both the treatment and control periods. 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.
Findings 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 and 61% of participants reported they would use magnesium in the future. Effects were observed within two weeks.
Interpretation 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.