The goal of this clinical trial is to evaluate whether magnesium supplementation can improve cognitive function in patients with depression receiving fluoxetine therapy. It also aims to assess its effect on serum brain-derived neurotrophic factor (BDNF) levels in adult patients with depression.

The main questions it aims to answer are:

• Does magnesium supplementation improve cognitive function in patients with depression receiving fluoxetine?
• Does magnesium supplementation increase serum BDNF levels in these patients? Researchers will compare patients receiving fluoxetine with magnesium supplementation to those receiving fluoxetine alone to determine whether magnesium provides additional benefits.

Participants will:

• Receive fluoxetine therapy with or without magnesium supplementation for 6 weeks
• Undergo cognitive assessment using the Montreal Cognitive Assessment (MoCA) at baseline and after treatment
• Provide blood samples for measurement of serum BDNF levels at baseline and after 6 weeks

Depression is associated with persistent cognitive impairment, including deficits in attention, memory, and executive function, which may not fully improve with standard antidepressant treatment. These cognitive deficits contribute to functional disability and reduced quality of life. Fluoxetine, a selective serotonin reuptake inhibitor, is widely used as first-line therapy for depression. However, its effects on cognitive function are inconsistent, and additional strategies are needed to enhance cognitive recovery.

Magnesium plays an important role in neurobiological processes, including modulation of NMDA receptors and synaptic plasticity, and has been proposed as an adjunctive treatment in depression. It may influence neuroplasticity-related pathways, including brain-derived neurotrophic factor (BDNF).

This study is a randomized, single-blind, controlled clinical trial with a pretest-posttest design conducted in adult patients with depression receiving fluoxetine therapy. Participants are allocated into two parallel groups: an intervention group receiving oral magnesium supplementation (350 mg/day) in addition to fluoxetine, and a control group receiving fluoxetine alone.

Cognitive function is evaluated using a standardized cognitive assessment tool, and serum BDNF levels are measured using laboratory-based assays at baseline and after a 6-week intervention period.

This study aims to explore the potential role of magnesium as an adjunctive therapy to enhance neurocognitive outcomes and to provide insight into the relationship between neuroplasticity biomarkers and cognitive improvement in patients with depression.

Inclusion Criteria:

• Adult patients aged 18-60 years
• Diagnosed with major depressive disorder based on clinical assessment
• Receiving fluoxetine therapy
• Able to understand and provide informed consent

Exclusion Criteria:

• History of other major psychiatric disorders (e.g., schizophrenia, bipolar disorder)
• Severe medical or neurological illness
• Use of other psychotropic medications that may affect cognitive function
• Known hypersensitivity to magnesium
• Pregnancy or breastfeeding
• Inability to complete cognitive assessment

Individual participant data will not be shared because there is no plan for public data sharing for this study.

This is a single-blind study in which participants are unaware of their group allocation.