l-Methylfolate as Adjunctive Therapy for SSRI-Resistant Major Depression: Results of Two Randomized, Double-Blind, Parallel-Sequential Trials

Abstract

Patients with major depression who have an insufficient response to selective serotonin reuptake inhibitors (SSRIs) may benefit from the addition of 15 mg/day of l-methylfolate, the only form of folate that crosses the blood-brain barrier. Adding 7.5 mg/day was no more effective than adding placebo, but 15.0 mg/day plus ongoing SSRI treatment produced a 32% response rate, compared to 15% for augmentation with placebo. Side effects in the two groups were comparable in type and frequency.