Data Affirms Long Term Benefit of Adding L-methylfolate to An Antidepressant — Genetic Markers Identified, BMI Possible Predictor of Efficacy

LAS VEGAS--(BUSINESS WIRE)--

Data presented today at the 24^th annual U.S. Psychiatric and Mental Health Congress add to the body of evidence suggesting that Deplin^® (L-methylfolate 15 mg) is an effective and safe agent for the nutritional management of metabolic imbalances in major depressive disorder (MDD) when used in addition to an antidepressant.

Two poster presentations on L-methylfolate authored by Dr. John Zajecka, Associate Professor of Psychiatry and Director of the Depression Treatment and Research Center at Rush University Medical Center in Chicago, and Dr. George Papakostas, Associate Professor of Psychiatry at Harvard Medical School and Director of Treatment-Resistant Depression Studies in the Department of Psychiatry of Massachusetts General Hospital in Boston, were presented at the Congress. Both posters were based on follow-up analysis of data initially presented at the American Psychiatric Association annual meeting in May.¹

Biomarker Findings

The first study, authored by Dr. Papakostas, evaluated the impact of Deplin^® (L-methylfolate 15mg) in addition to a selective serotonin reuptake inhibitor (SSRI) with specific biomarkers in a double-blind trial. 75 outpatients with SSRI-resistant MDD were enrolled in a 60-day study, divided into two, 30-day evaluation periods. Patients were randomized to receive Deplin^® (L-methylfolate 15mg) in addition to an antidepressant for 60 days; placebo in addition to an antidepressant for 30 days followed by Deplin^® (L-methylfolate 15mg) in addition to an antidepressant for 30 days; or placebo in addition to an antidepressant for 60 days. The SSRI doses remained constant during the double-blind phase of the study. The results of the trial indicated significantly greater benefits with Deplin^® (L-methylfolate 15mg) with an antidepressant versus placebo plus antidepressant in 30 days. Secondary genomic and biomarker endpoints were evaluated to determine if there was a difference in the impact of Deplin^® on results.

Genomic Findings

There was a numerically greater benefit in patients receiving Deplin^® (L-methylfolate 15mg and an antidepressant in patients who had an allelic variant in MTHFR (methylentetrahydrofolate reductase) C677T genotype (reductions in Hamilton Depression Rating Scale-17 [HDRS-17] scores of 3.44 for ‘T' allele vs. 1.41 for ‘CC' allele [considered a “normal” allele]).

BMI as an Indicator

Obese patients, defined as having a Body Mass Index (BMI) greater than or equal to 30, receiving Deplin^® (L-methylfolate 15mg) and an antidepressant experienced a significantly greater reduction in depression scores (reduction in HDRS-17 scores of 4.60 points; p = 0.001) compared to those with a BMI <30 receiving placebo in addition to an antidepressant (increase of +1.83, p = 0.298).

These findings suggest that Deplin^® in addition to an SSRI may represent an effective, safe, and well tolerated therapeutic strategy for MDD patients who are SSRI partial- and non-responders, particularly in patients with an MTHFR genetic variant or a BMI ≥ 30.

No difference in side effects was reported between the groups administered Deplin^® in addition to an antidepressant compared to placebo in addition to an antidepressant.

Long Term Maintenance

In a separate presentation authored by Dr. Zajecka, subjects who completed one of two double blind, placebo-controlled studies of Deplin^® in addition to an SSRI were offered the option of enrolling in a 12-month open-label, maintenance phase with Deplin^® (L-methylfolate 15mg) in addition to an SSRI. Thirteen subjects who achieved remission during the initial double-blind study phase entered this open-label phase and received L-methylfolate 15mg with their antidepressant. Follow-up visits occurred every 12 weeks for safety, tolerability, relapse/recurrence (defined as Hamilton Depression Rating Scale-17 scores >15), and sustaining remission (defined as Hamilton Depression Rating Scale-17 scores ≤ 7) at study conclusion.

No subject experienced relapse or recurrence at any time point, and 54% of subjects sustained full remission at 12 months. There were no serious adverse events and no discontinuations due to adverse events reported during the 12-month open-label treatment.

These data suggest that the use of Deplin^® (L-methylfolate 15mg) in addition to an SSRI in inadequate responders is safe and well tolerated. Further, therapy with Deplin^® may assist in maintaining long term benefits in the majority of patients with MDD treated for 12 months following acute remission.

Folate Deficiency & L-methylfolate

Scientists have long suspected an association between a deficiency in the bioactive form of folate and depression, and studies have been conducted to determine if the active form of folate can improve depression symptoms.²

L-methylfolate has been categorized as a Trimonoamine Modulator (TMM) because it is the only form of folate that can cross the blood-brain barrier to help regulate serotonin, norepinephrine and dopamine, the neurotransmitters associated with mood.³ In these studies Deplin^® (L-methylfolate) was chosen because of its ability to cross the blood brain barrier, its bioavailability and safety profile.

About Deplin^®

Deplin^® is a medical food available by prescription for the clinical dietary management of the metabolic imbalances associated with depression. It should be used only under medical supervision.⁴

For more information visit http://www.deplin.com or see full prescribing information.

¹ Papakostas, George. American Psychiatric Association 2011 Annual Meeting. Honolulu, HI. 18 May 2011. Scientific and Clinical Report Presentation. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

² Stahl SM. Novel Therapeutics for Depression: L-methylfolate as a Trimonoamine Modulator and Antidepressant Augmenting Agent. CNS Spectrums. 2007;12(10):739-44.

³ Stalh SM. op cit.

⁴ Deplin® Package Insert, Pamlab LLS 04/2011