Magnesium supplementation as an adjunct to fluoxetine therapy for depression

To evaluate the effectiveness of magnesium supplementation as an adjunct to fluoxetine therapy for improving depressive symptoms and serum serotonin levels in patients with depression.

Consecutive patients aged 18 to 45 years who had been prescribed fluoxetine therapy for new-onset or chronic depression were recruited between November 2024 and February 2025 at the outpatient psychiatry clinic of Wahidin Sudirohusodo General Hospital and three affiliated hospitals in Makassar, Indonesia. Participants were randomised in an alternating sequence to receive either fluoxetine 20 mg/day alone or in combination with oral magnesium supplementation 250 mg/day. Outcomes were assessed at baseline and week 6. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Blood samples were collected to measure serum serotonin levels.

In total, 32 women and 8 men who received either fluoxetine alone (n = 20) or in combination with magnesium (n = 20) were included in the analysis. Both groups showed significant reductions in HDRS total score from baseline to week 6 (p < 0.001), but changes in serum serotonin level were not significant in either group. The reduction in HDRS total score was greater in the intervention group than in the control group (-6.35 vs -2.80, p < 0.001), particularly in the domains of mood and insomnia. The median reduction in HDRS total score was greater in the intervention group than in the control group (-6 vs -2, p < 0.001). The group effect remained significant (F(1,30) = 33.51, partial η² = 0.528, p < 0.001) after adjustment for baseline HDRS score and demographic covariates, indicating a large effect size.

Magnesium supplementation as an adjunct to fluoxetine therapy improves HDRS total score in patients with depression.