Effect of combination therapy of methylfolate with antidepressants in patients with depressive disorder.

Objective: To determine the relative effectiveness of combination therapy of antidepressants with low-dose methylfolate versus antidepressant monotherapy in patients with depressive disorder.

Methods: In an open-label clinical trial, forty-four patients with depressive disorder (6A70, 6A71, and 6A72 according to ICD-11) received an evidence-based antidepressant therapy (either escitalopram 10-20 mg, sertraline 50-100 mg, fluoxetine 20-40 mg, duloxetine 30-60 mg, mirtazapine 15-30 mg, venlafaxine 75-150 mg, trazodone 50-100 mg, amitriptyline 25-75 mg, or clomipramine 25-75 mg orally daily for 4 weeks). The experimental group, Group B was additionally given a dose of methylfolate 800 µg daily for four weeks. The psychometric testing of depression was achieved through administration of Patient Health Questionnaire-9 (PHQ-9) on days 0, 14, and 28, to find the improvement in the depressive score on day 28, the remission rate on day 28, and decrease in the time lag on day 14. Adverse effects were analyzed by self-assessment questionnaire to observe the tolerability. The paired sample t-test and the independent sample t-test were applied for analysis by using SPSS v27.0. The p-value ≤ 0.05 was considered statistically significant.

Results: On day 28, patients on low dose methylfolate and antidepressant combination therapy showed a 40.33% improvement in depression symptoms, compared to 26.43% in patients on antidepressant monotherapy (p-value < 0.05). This treatment strategy had no effect on the time-lag of outcomes on day 14 and the remission rate on day 28 was not found statistically significant. Only one patient reported insomnia, while another mentioned irritability.

Conclusion: Combination therapy of antidepressants with low-dose methylfolate may provide a safe and effective treatment strategy for patients with depressive disorder.

Clinical Trial Identifier: NCT05931965.

Clinicaltrials: gov. https://classic.

Clinicaltrials: gov/ct2/show/NCT05931965.