Breakthrough Study Shows Benefits Of Adjunctive L-Methylfolate In The Treatment Of SSRI-Resistant Major Depressive Disorder
"Deplin® can be part of a novel approach to depression therapy that is effective in patients that do not respond to traditional SSRI's, as well as relatively safe and well-tolerated compared to almost all alternative options" said Dr. George Papakostas, lead author of the study. "The efficacy to the molecule has been proven in a randomized controlled trial examining at 15mg daily dose, and we are eager to see how it can benefit certain subsets of the depressive population with SSRI-resistant depression."
"The results of this clinical trial are very encouraging," said Dr. Maurizio Fava, the study's lead investigator. "It will be exciting to see additional research involving L-methylfolate as an adjunct therapy for MDD. If continued to be proven to help patients achieve a superior response in the treatment of depression, this could be a true game-changer in the field."
Two double-blind studies involved 223 patients with SSRI-resistant MDD and found that 15mg per day of adjunctive L-methylfolate can be a useful treatment strategy for SSRI partial and non-responders with MDD, while 7.5mg daily did not appear to be sufficient to treat MDD.
In the first trial, 148 outpatients with SSRI-resistant MDD were enrolled in a 60-day multi-center study divided into two, 30-day periods (phases I and II). Patients were randomized in a 2:3:3 fashion to receive either adjunctive L-methylfolate for 60 days (7.5mg/day, phase I; 15mg/day, phase II), adjunctive placebo for 30 days followed by adjunctive L-methylfolate for 30 days (7.5 mg/day), or adjunctive placebo for 60 days. SSRI doses were kept constant during the double-blind phase of the study. The second trial, which involved a total of 75 patients, was identical in design to the first, except for a target dose of 15mg/day of adjunctive L-methylfolate throughout both phases.
While the first trial showed no difference in outcome between the adjunctive L-methylfolate 7.5mg/day and adjunctive placebo, the results of the second trial indicated significantly greater outcomes with adjunctive L-methylfolate 15mg/day versus adjunctive placebo on both co-primary outcome measures and a number of secondary outcome measures. Twice as many patients taking adjunctive L-methylfolate 15mg/day achieved response in 30 days (response: ≥50% reduction in depressive symptoms) and experienced 84% greater reduction in depressive symptoms compared to patients given adjunctive placebo (p=0.04, p=0.05 respectively). The number needed to treat for response was between 5 and 6 in favor of adjunctive L-methylfolate 15mg/day.
There were no statistically significant differences in discontinuation due to adverse events between L-methylfolate and placebo-treated patients.