l-Methylfolate as Adjunctive Therapy for SSRI-Resistant Major Depression: Results of Two Randomized, Double-Blind, Parallel-Sequential Trials
Introduction
These two sequential randomized controlled trials investigated the efficacy of l-methylfolate augmentation in patients with major depressive disorder who had partial or no response to selective serotonin reuptake inhibitors (SSRIs). The studies used a novel sequential parallel comparison design to enhance statistical power and provide definitive evidence for this promising adjunctive treatment.
Background and Rationale
The Challenge of Treatment-Resistant Depression
More than half of all patients treated with antidepressant monotherapy fail to experience remission of their major depressive episode. This creates an urgent need for safe, well-tolerated, and effective treatments for antidepressant-resistant depression.