New findings from Deplin clinical trial on major depressive disorder presented at NCDEU

Jun 14 2011

New findings from a multi-center, randomized, placebo-controlled clinical study of Deplin^® 15mg (L-methylfolate) added to commonly prescribed antidepressants known as selective serotonin reuptake inhibitors (SSRIs) showed that all patients who achieved remission at 30 days using Deplin^® 15mg adjuvant therapy, and who chose to enter a 12 month maintenance phase, maintained their remission after a year of treatment.

The 223 patient study was presented today at NCDEU, a scientific congress sponsored by the American Society of Psychopharmacology, meeting in Boca Raton this week. This study supports the growing the body of evidence for the metabolic management of major depressive disorder with Deplin^® (L-methylfolate), a medical food, administered in combination with antidepressants.

Outcomes

As previously reported at the American Psychiatric Association 2011 Annual Meeting, 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. Both primary outcome measures used in the study achieved statistical significance.

The data showed that 32.3 percent of patients who received adjunctive therapy with 15 mg of Deplin^® combined with an SSRI responded after 30 days of treatment compared to 14.6 percent of patients who received SSRI with placebo.

A greater reduction in depressive symptoms using the mean change in HDRS-17 was found in the adjuvant Deplin^® arm compared to the adjuvant placebo arm--5.58 points versus 3.04 points.

"Adjunctive Deplin^® 15mg helped patients with major depressive disorder experiencing an inadequate response to an SSRI achieve the benefits of their antidepressant therapy during the double-blind trial and maintain the benefits of antidepressant therapy after continuation in a 12 month open label phase," said Dr. John Zajecka, Associate Professor of Psychiatry and Clinical Director of the Depression Treatment and Research Center at Rush University Medical Center in Chicago.

A secondary outcomes measure was remission status using the HDRS-17 (a final score of 7 or less).

On remission, there was a numerically important difference in favor of Deplin^® + SSRI compared to placebo + SSRI in the double-blind phase. Although not statistically significant after the 30-day evaluation period, of patients who achieved remission during the double-blind phase and entered into the 12 month, open label maintenance phase, none relapsed.

Personalized Medicine: Genetic Findings

Four genetic inborn errors of folate metabolism, including methyltetrahydrofolate reductase (MTHFR) enzyme were evaluated. A significant treatment effect with adjuvant Deplin^® compared to adjuvant placebo was found after adjusting for genotypes in the double blind 30-day trial (p<.05).

These polymorphisms create poor folate metabolizers who are at greater risk of depression and lack of response to antidepressants. These errors limit their ability to convert folate from food or synthetic folic acid, found in vitamin supplements, to L-methylfolate, the only form of folate the brain can use immediately to regulate neurotransmitters.

"In patients with inadequate response to SSRI monotherapy for depression, the addition of L-methylfolate 15mg (Deplin^®) may offer a personalized approach to improve responses to antidepressant therapy in genetic errors of folate metabolism such as the MTHFR polymorphism," said Dr Zajecka. "Although this study is speculative, it represents promise in a genotypically defined subgroup of patients and an option for personalized medicine in major depression."