L-methylfolate Plus Antidepressant Improves MDD
It is reported that approximately 70 percent of major depressive disorder (MDD) patients have a genetic abnormality that results in an imbalance of L-methylfolate. (2) Adjunctive L-methylfolate administered early in therapy has demonstrated that there are clear synergies between antidepressant drugs and L-methylfolate that result in better patient outcomes and earlier in the course of treatment.
The study was a retrospective two-arm chart review of 242 adults, ages 18-70, diagnosed with MDD and experiencing some degree of functional impairment (Clinical Global Impression – Severity (CGI-S) score of four (moderately ill) or five (markedly ill)) Charts were divided into those patients who were treated with SSRI/SNRI plus dietary management using L-methylfolate at the start of treatment and a control arm of 147 patients using SSRI/SNRI monotherapy.
More than two and a half times as many patients in the combination SSRI/SNRI drug + L-methylfolate medical food arm achieved major improvement than those in the control arm. 18.5 percent of the L-methylfolate and antidepressant treated patients showed a major improvement at 60 days in depression symptoms represented by a 2 points or greater reduction in CGI-S versus 7.04 percent of the control group (p = 0.01).
Forty percent of combination patients rated severe (CGI-S = 5) improved significantly within 60 days compared to 16.3 percent of patients in the control group (p= 0.02). Median time to a 2-point or greater CGI-S reduction in the combination group was 177 days compared to 231 days for the control group (p= 0.03) and discontinuation rates due to adverse events were significantly lower in the combination group (17.9 percent) versus the antidepressant monotherapy group (34 percent) (p=0.0078), although the overall rates of adverse events in both groups were not statistically different
L-methylfolate is the only form of folate that crosses the blood-brain barrier to help regulate neurotransmitters associated with depression. According to the authors the use of adjunctive L-methylfolate along with an antidepressant may represent a paradigm shift in the therapy of major depressive disorder.
References:
1. Ginsberg LD, Oubre A, Daoud Y. Innov Clin Neurosci. 2011;8(1):19-28.
2. Stahl SM. CNS Spectrums. 2007;12(10):739-44.