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Magnesium supplementation as an adjunct to fluoxetine therapy for depression.

  • 2026-03-31
  • East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan 36(1)
    • A S Walyddaini
    • S T Lisal
    • Ilhamuddin
    • A A Zainuddin
    • A J Tanra
    • Y Widianingsih
    • S Syamsuddin

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 32
Population
40 patients with depression (32 women and 8 men) aged 18 to 45 years
Methods
Randomised in an alternating sequence to receive either fluoxetine 20 mg/day alone or in combination with oral magnesium supplementation 250 mg/day
Blinding
Open-label
Duration
6 weeks

Objectives

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.

Methods

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.

Results

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.

Conclusion

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

Research Insights

  • Magnesium→Improved Depressive Symptoms

    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)

    Effect
    Beneficial
    Effect size
    Large
    Dose
    250 mg/day
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