Effect of L Methyl Folate as an Add on Antidepressant Therapy in Patients with Major Depressive Disorder in Indian Population: A Randomized, Double Blind, Placebo Controlled Study

This study will use a prospective, randomized, double-blind, placebo-controlled design to investigate the effects of add-on L-methyl folate therapy over 60 days on patients with major depressive disorder (MDD). The primary aim is to assess changes in depressive symptoms using the Hamilton Depression Rating Scale (HAMD). Secondary objectives include evaluating changes in serum BDNF levels, changes in serum SAM levels, changes in serum folate and Vitamin B12 levels and the Montgomery–Asberg Depression Rating Scale (MADRS). Participants clinically diagnosed with major depressive disorder and on stable antidepressant therapy for at least 4 weeks will be screened in the psychiatry outpatient department at AIIMS, New Delhi. Eligible participants meeting the inclusion criteria will be randomly assigned to the treatment group, receiving L-methyl folate 15 mg, or the placebo group, receiving a matching placebo. Both groups will continue their ongoing antidepressant regimen for 60 days. At enrollment, demographic data, depression scores, and antidepressant treatment-related data will be collected. Blood samples will be taken to measure depression-related markers (BDNF, SAM, folate and vitamin B12). After 60 days of supplementation, all baseline parameters will be reassessed. Changes in depression scores from baseline to post-supplementation will be calculated and presented as mean (SD). Any adverse events during the intervention will be monitored and reported to the corresponding authorities.