Randomized Study Combining L-Methylfolate With Antidepressant Shows Significant Boost in Patient Response

HONOLULU--(BUSINESS WIRE)--May 18, 2011 - Results were reported today in a multi-center, randomized, placebo-controlled clinical study of adding Deplin® (15 mg L-methylfolate) compared to adding placebo in patients with major depressive disorder with an inadequate response to common antidepressants known as selective serotonin reuptake inhibitors (SSRIs). Adjunctive clinical dietary management with Deplin® 15 mg significantly improved the benefits of the antidepressant therapy compared to continued antidepressant monotherapy.

According to the landmark Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, nearly 70 percent of patients treated with initial monotherapy will fail to achieve remission of their major depression.1 Depression, a chronic, recurrent disease, is one of the nation's most common ailments, affecting more than 18 million people in the United States.2

The 223 patient study was presented today at an oral scientific report at the American Psychiatric Association Annual Meeting. This study validates the body of evidence supporting metabolic management with L-methylfolate, a medical food, administered in combination with antidepressants.3,4

Outcomes

Two primary outcome measures were used in the study: Rates of response (50 percent reduction) in the 17-question Hamilton Depression Rating Scale (HDRS-17) and degree of improvement (mean change) in HDRS-17.

The data showed significantly higher response rates (50% reduction in HDRS-17) after 30 days in patients who received adjunctive Deplin® 15 mg with an SSRI compared to patients who received SSRI and adjunctive placebo. There was also a significantly greater reduction in depressive symptoms as measured by mean change in HDRS-17 in the adjuvant Deplin® 15 mg arm compared to the adjuvant placebo arm.

Before beginning the study, all patients had to demonstrate inadequate response to one or two SSRIs. Antidepressants included in the randomized trial were therapeutic doses of fluoxetine, citalopram, paroxetine, escitalopram, and sertraline. Once the patients entered into the study, the SSRI doses remained constant. There was no significant difference in side effects reported with adjunctive Deplin® 15 mg. Rates of discontinuation due to adverse events were no different in the Deplin® 15 mg and SSRI group compared to the placebo and SSRI group.

Additional Findings

Secondary outcomes measures included changes in scores on the self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR) and the Clinical Global Impression Severity Scale (CGI-S). Both of these measures showed significantly greater efficacy in favor of the Deplin® with SSRI group.

About the Study

The two trials in this study used a novel sequential parallel comparison design (or SPCD). Results from the first of two trials (n = 148) was used to inform the dosing of the second trial (n = 75). The first trial found 7.5 mg dosing of L-methylfolate and an SSRI was not significantly different in efficacy compared to placebo and SSRI. The second trial found 15 mg dosing L-methylfolate and an SSRI was significantly superior on response rates and degree of improvement in depressive symptoms compared to placebo and SSRI.

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.3,4,5,6,7 Up to 70 percent of people who suffer from depression may have a specific genetic factor that compromises their ability to convert folate from food or synthetic folic acid into the bioactive form, L-methylfolate.

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.8 In this first randomized, placebo controlled study, L-methylfolate was chosen because of its ability to cross the blood brain barrier, its bioavailability and safety benefits compared to folic acid and other synthetic folates.

About Deplin®

Deplin® is a prescription medical food for the clinical dietary management of the metabolic imbalances associated with depression. Use under medical supervision.9

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

1 Trivedi M, Rush A, Wisniewski S, et al. Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice. Am J Psychiatry. 2006;163:28-40.

2 The National Institute of Mental Health (NIMH). (n.d.). The Numbers Count: Mental Disorders in America. Retrieved from: http://www.nimh.nih.gove/health/publications/the-numbers-count-mental-disorders-in-america/index.shtml.

3 Ginsberg LD, Oubre A, Daoud Y. L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode. Innov Clin Neurosci. 2011;8(1):19-28.

4 Godfrey P, Crellin R, Toone BK, et al. Enhancement of recovery from psychiatric illness by methylfolate. Br J Psychiatry. 1992;161:126-7.

5 DiPalma C et al. Is Methylfolate Effective in Relieving Major Depression in Chronic Alcoholics? A Hypothesis of Treatment. Curr Ther Res. 1994;55(5):559-68.

6 Guaraldi et al. A Open Trial of Methyltetrahydrofolate in Elderly Depressed Patients. Annals Clin Psych. 1993;5(2):101-5.

7 Passeri M et al. 'Oral 5'-Methyltetrahydrofolic Acid in Senile Organic Mental Disorders With Depression: Results of a Double-blind Multicenter Study. Aging Clin Exp Res. 1993;5(1):63-71.

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

9 Deplin® Package Insert. Pamlab, L.L.C. 04/2011.

Contact: For Pamlab, L.L.C.
Michael Durand, 917-856-5373
deplinpr@pamlab.com

 

 

Posted: May 2011

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