According to a new study published in PLOS One, over-the-counter (OTC) magnesium may be an effective treatment for adults with mild-to-moderate depression.

While previous studies have alluded to an association between magnesium intake and depression, particularly in seniors with type 2 diabetes and patients with fibromyalgia, the results have been inconsistent and often varied on the salt used in the supplement (positive with magnesium chloride and magnesium citrate; negative with magnesium oxide). In this open-label, blocked, randomized, cross-over trial, the researchers aimed to find out whether the use of OTC magnesium chloride could improve symptoms of depression in 126 adults patients with Patient Health Questionnaire-9 (PHQ-9) scores of 5–19. Patients received either 248mg of elemental magnesium daily (four 500mg tablets of magnesium chloride) or a control (no treatment) for 6 weeks; bi-weekly phone calls were used to assess depression symptoms.

The primary outcome for the study was the “net difference in the change in depression symptoms from baseline to the end of each treatment period.” Changes in anxiety symptoms, adherence, adverse effects, and intention of future use of magnesium supplements were all secondary outcomes. Compared to no treatment, consumption of magnesium chloride for 6 weeks was associated with a significant net improvement in PHQ-9 scores and Generalized Anxiety Disorders-7 scores among the 112 patients with analyzable data (PHQ-9: –6.0 points [CI –7.9, –4.2; P<0.001]; GAD-7: –4.5 points [CI –6.6, –2.4; P<0.001]). 

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The supplements were found to be well-tolerated with an average adherence of 83% by pill count; 61% of patients reported they would use the supplements in the future. Similar effects were seen across all subgroups (age, gender, depression severity, magnesium level, concomitant antidepressants) with most patients seeing improvement in symptoms within two weeks of treatment. The effect was also found to diminish within two weeks of discontinuing supplementation. With regards to adverse effects, only one patient discontinued treatment due to nausea and lethargy.

Given these results, the authors noted that the use of magnesium supplementation could help break through some of the barriers individuals may face when considering antidepressant therapy. Magnesium supplementation is generally considered safe for patients with normal renal function, for those who are not taking interacting medications, and for those who consume doses below the upper tolerable limit set by the Institute of Medicine (350mg elemental magnesium/day). In addition, the supplement does not carry the stigma sometimes associated with antidepressant treatment and is easily accessible without a prescription.

“While the cross-over design of this trial is robust in controlling for internal biases, it would be reassuring to see the results replicated in larger clinical trials that test long term efficacy and provide additional data on subgroups. However, this efficacy trial showed magnesium supplements may be a fast, safe, and easily accessible alternative, or adjunct, to starting or increasing the dose of antidepressant medications,” wrote the authors.

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