Effects of magnesium supplementation on serum brain-derived neurotrophic factor levels and cognitive function in patients undergoing fluoxetine therapy for depression.
- 2026-06-30
- 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(2)
- N J Noor
- S Syamsuddin
- K Liaury
- S Tawali
- I Idris
- I Azis
- S T Lisal
- PubMed: 42374947
- DOI: 10.12809/eaap2617
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 40
- Population
- Outpatients aged 18 to 50 years diagnosed with depression who were receiving fluoxetine treatment at various hospitals in Makassar, Indonesia
- Methods
- Randomized allocation to control group (fluoxetine alone for 6 weeks) or treatment group (fluoxetine plus 350 mg oral magnesium once daily for 6 weeks); BDNF measured by ELISA; cognitive function by MoCA-Ina
- Blinding
- Open-label
- Duration
- 6 weeks
- Funding
- Unclear
Objectives
To evaluate the effects of magnesium supplementation as an adjunct to fluoxetine on serum brain-derived neurotrophic factor (BDNF) levels and cognitive function in patients with depression.Methods
Outpatients aged 18 to 50 years diagnosed with depression who were receiving fluoxetine treatment at various hospitals in Makassar, Indonesia, between July and August 2025 were invited to participate. Participants were randomly allocated to either the control group, which received fluoxetine therapy alone for 6 weeks, or the treatment group, which received fluoxetine therapy plus 350 mg of oral magnesium supplementation once daily for 6 weeks. Patients were assessed at baseline and 6 weeks. BDNF levels were measured using peripheral venous blood samples. Serum BDNF concentrations (in pg/mL) were quantified using an enzyme-linked immunosorbent assay kit. Cognitive function was assessed using the validated Indonesian version of the Montreal Cognitive Assessment (MoCA-Ina).Results
In total, 40 participants were randomly allocated to either the control group (n = 20) or the treatment group (n = 20). Both groups had significant improvements in MoCA-Ina scores from baseline to week 6 (both p < 0.001), but the improvement was greater in the treatment group (4.8 vs 1.35, p < 0.001), particularly in the domains of attention (from 2.90 to 4.05, p < 0.001) and memory (from 2.25 to 3.85, p < 0.001). At week 6, scores were significantly higher in the treatment group in the domains of attention (4.05 vs 3.10, p = 0.002), memory (3.85 vs 2.70, p < 0.001), and orientation (5.75 vs 5.05, p < 0.001). Although improvement in MoCA-Ina scores was greater in the treatment group, change in serum BDNF levels between groups was not significant (60.59 vs -29.01 pg/mL, p = 0.584). Changes in serum BDNF levels were more strongly correlated with changes in MoCA-Ina scores in the treatment group (ρ = 0.667, p = 0.001) than in the control group (ρ = 0.483, p = 0.031).Conclusion
Magnesium supplementation as an adjunct to fluoxetine was associated with greater improvement in cognitive function than fluoxetine alone in patients with depression. Changes in serum BDNF levels were positively associated with cognitive improvement, particularly in the treatment group. These findings suggest a role for magnesium in enhancing cognitive recovery, possibly through modulation of neuroplasticity-related pathways.Research Insights
particularly in the domains of attention (from 2.90 to 4.05, p < 0.001) ... At week 6, scores were significantly higher in the treatment group in the domains of attention (4.05 vs 3.10, p = 0.002)
- Effect
- Beneficial
- Effect size
- Small
- Dose
- 350 mg/day
Both groups had significant improvements in MoCA-Ina scores from baseline to week 6 (both p < 0.001), but the improvement was greater in the treatment group (4.8 vs 1.35, p < 0.001)
- Effect
- Beneficial
- Effect size
- Moderate
- Dose
- 350 mg/day
particularly in the domains of ... memory (from 2.25 to 3.85, p < 0.001) ... At week 6, scores were significantly higher in the treatment group in the domains of ... memory (3.85 vs 2.70, p < 0.001)
- Effect
- Beneficial
- Effect size
- Small
- Dose
- 350 mg/day
At week 6, scores were significantly higher in the treatment group in the domains of ... orientation (5.75 vs 5.05, p < 0.001)
- Effect
- Beneficial
- Effect size
- Small
- Dose
- 350 mg/day
change in serum BDNF levels between groups was not significant (60.59 vs -29.01 pg/mL, p = 0.584)
- Effect
- Neutral
- Effect size
- Small
- Dose
- 350 mg/day