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The article you requested is

Effect of Adjunctive l-Methylfolate 15 mg Among Inadequate Responders to SSRIs in Depressed Patients Who Were Stratified by Biomarker Levels and Genotype: Results From a Randomized Clinical Trial

J Clin Psychiatry
Copyright 2014 Physicians Postgraduate Press, Inc.

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Objective: Specific genetic or biological markers may predict inadequate response to therapy for major depressive disorder (MDD). The objective of the current post hoc analysis was to evaluate the effect of specific biological and genetic markers on the antidepressant efficacy of adjunctive l-methylfolate 15 mg versus placebo from a trial of inadequate responders to selective serotonin reuptake inhibitors (SSRIs).

Method: The double-blind, randomized, placebo-controlled trial used the sequential parallel comparison design. Outpatients with SSRI-resistant MDD (DSM-IV criteria) received l-methylfolate 15 mg/d for 60 days, placebo for 30 days followed by l-methylfolate 15 mg/d for 30 days, or placebo for 60 days. The effects of baseline levels of select biological and genetic markers individually and combined on treatment response to l-methylfolate versus placebo were evaluated; the primary response measure was the 28-Item Hamilton Depression Rating Scale (HDRS-28). The first patient was enrolled July 14, 2009, and the last patient completed April 28, 2011.

Results: Seventy-five patients were enrolled. Patients with specific biological (body mass index ≥ 30 kg/m2, elevated plasma levels of high-sensitivity C-reactive protein or 4-hydroxy-2-nonenal, low S-adenosylmethionine/
S-adenosylhomocysteine ratio) and genetic markers at baseline had significantly (P .05) greater pooled mean change from baseline on the HDRS-28 with l-methylfolate versus placebo. Pooled mean change from baseline on the Clinical Global Impressions-Severity of Illness scale was significantly (P < .05) greater with l-methylfolate versus placebo for most genetic markers. Most combinations of baseline biological and genetic markers predicted significantly (P .05) greater reductions in pooled mean change from baseline in HDRS-28 scores with l-methylfolate versus placebo.

Conclusions: Biomarkers associated with inflammation or metabolism and genomic markers associated with l-methylfolate synthesis and metabolism may identify patients with SSRI-resistant depression who are responsive to adjunctive therapy with l-methylfolate 15 mg. Confirmatory studies are needed.

Trial Registration: ClinicalTrials.gov identifier: NCT00955955

J Clin Psychiatry 2014;75(00):000–000

Submitted: December 17, 2013; accepted March 6, 2014.

Online ahead of print: April 15, 2014 (doi:10.4088/JCP.13m08947).

Corresponding author: George I. Papakostas, MD, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, One Bowdoin Sq, 6th Fl, Boston, MA 02114 (gpapakostas@partners.org).