Psychiatry · Medical Literature
Effects of magnesium supplementation on serum brain-derived neurotrophic factor levels and cognitive function in patients undergoing fluoxetine therapy for depression.
Abstract
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. 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). 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). 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.
Clinical relevance
Does adjunctive oral magnesium supplementation (350 mg/day for 6 weeks) enhance serum BDNF levels and cognitive function in outpatients with depression who are receiving fluoxetine monotherapy? __SNAPSHOT__ {"studyDesign":"Randomized controlled trial (two-arm, parallel-group)","setting":"Outpatient psychiatry clinics at various hospitals in Makassar, Indonesia; July–August 2025","sampleSize":"n = 40 (intervention: n = 20; control: n = 20)","population":"Outpatients aged 18–50 years with a diagnosis of depression who were already receiving fluoxetine therapy; recruited over a two-month window","intervention":"Fluoxetine therapy plus oral magnesium supplementation 350 mg once daily for 6 weeks","comparator":"Fluoxetine therapy alone for 6 weeks","primaryOutcome":"Serum BDNF concentration (pg/mL, measured by ELISA from peripheral venous blood) and cognitive function assessed by the validated Indonesian-language Montreal Cognitive Assessment (MoCA-Ina); both measured at baseline and week 6","followUp":"6 weeks","fundingSource":"Not reported"}
Key findings
Both the magnesium-plus-fluoxetine group and the fluoxetine-alone group demonstrated statistically significant within-group improvements in MoCA-Ina scores from baseline to week 6 (both p < 0.001). The abstract was truncated before reporting the between-group comparison for MoCA-Ina scores, serum BDNF results, between-group BDNF comparisons, absolute effect sizes, confidence intervals, or NNT/NNH values. Accordingly, no between-group differences, absolute or relative effect sizes, confidence intervals, or adverse event data can be reported for this summary. All such values are not reported in the available abstract.
Practice implications
The study establishes that both treatment groups experienced statistically significant within-group improvements in MoCA-Ina scores over 6 weeks, but whether adjunctive magnesium produced superior cognitive outcomes compared to fluoxetine alone cannot be determined from the available abstract, as the between-group comparison was not included in the truncated text. Similarly, the critical question of whether magnesium augmentation meaningfully elevated serum BDNF levels above that achieved by fluoxetine monotherapy remains unanswered from the abstract alone. The findings apply narrowly to Indonesian outpatients aged 18–50 years with depression on fluoxetine; patients with treatment-resistant depression, comorbid medical illness, or those outside this age range were not represented. The within-group MoCA-Ina improvements observed in both arms are consistent with the known cognitive benefits of effective antidepressant therapy itself, precluding attribution of any improvement to magnesium without the between-group data. Clinical practice should not be modified on the basis of the truncated abstract alone. Review of the full published article is essential before drawing conclusions about adjunctive magnesium. Note: This summary is based solely on the truncated abstract provided; the full article was not accessible for review, representing a significant limitation. __LIMITATIONS__ Very small sample size (n = 40 total; n = 20 per arm) substantially limits statistical power and the ability to detect clinically meaningful between-group differences, increasing risk of both Type I and Type II errors.,Abstract was truncated; between-group comparisons for both primary outcomes (serum BDNF and MoCA-Ina) are not reported, making it impossible to determine whether adjunctive magnesium was superior to fluoxetine alone.,Extremely short recruitment window (July–August 2025, two months) and restricted geographic setting (Makassar, Indonesia) raise concerns about selection bias and limited generalizability to other populations or health systems.,Six-week follow-up is insufficient to assess durable cognitive or neurobiological effects of magnesium supplementation in a condition that often requires months of treatment.,The study appears to lack placebo control for the magnesium arm; absence of double-blinding is not stated in the abstract but, given no mention of blinding, the risk of performance and detection bias is high.,Baseline magnesium status of participants was not mentioned; without knowing whether patients were magnesium-deficient, the relevance of supplementation is uncertain.,Serum BDNF is a surrogate biomarker; its validity as a proxy for central BDNF signaling and its relationship to meaningful clinical outcomes (e.g., depression remission, functional recovery) remains debated.,Concomitant fluoxetine dosing, adherence, prior antidepressant exposure, and depression severity at baseline were not described in the abstract, representing important potential confounders.,Magnesium formulation (salt form, bioavailability) not specified.,Funding source is not reported; potential conflicts of interest cannot be assessed. __BOTTOM_LINE_CATEGORY__ low_certainty __BOTTOM_LINE__ This small randomized trial (n = 40) reported significant within-group improvements in MoCA-Ina cognitive scores in both the magnesium-augmented and fluoxetine-alone groups at 6 weeks, but the abstract was truncated before disclosing between-group comparisons for either cognitive function or serum BDNF — the two primary outcomes. No practice change is warranted; clinicians should access the full publication before drawing conclusions about adjunctive magnesium supplementation in depressed patients on fluoxetine.