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

Randomized clinical trial in adults with mild-to-moderate depression treated in outpatient primary care clinics at a single academic medical center in the United States. Participants were assigned to immediate versus delayed magnesium chloride treatment; baseline depressive and anxiety symptoms were in the mild-to-moderate range.

Oral magnesium chloride was given as four 500 mg tablets daily, providing 248 mg elemental magnesium per day for 6 weeks. The trial compared an immediate magnesium chloride treatment period with a delayed magnesium chloride period in a crossover-style design.

Magnesium chloride improved depressive and anxiety symptoms versus control and was well tolerated. The primary PHQ-9 outcome showed a net improvement of -6.0 points (95% CI -7.9, -4.2; P<0.001), and the GAD-7 showed a net improvement of -4.5 points (95% CI -6.6, -2.4; P<0.001). During magnesium treatment, PHQ-9 scores fell by -4.3 points versus -0.1 during control, and GAD-7 scores fell by -3.9 points versus +0.8 during control. Adherence by pill count was 83% in the immediate group and 82% in the delayed group; most adverse effects were not increased, although headache was slightly less frequent with magnesium (adjusted difference -0.14; 95% CI -0.25, -0.03; P=0.01).

The study was modest in size, with 62 and 64 participants in the active treatment sequences, and used relatively short 6-week treatment periods. It was conducted in a single U.S. academic primary care setting with a predominantly White sample, which limits generalizability. Outcomes were symptom scales and the design may be sensitive to period/carryover and expectancy effects.