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L-methylfolate Effective in the Treatment of MDD

November 9, 2010

Pharmacotherapy for major depressive disorder (MDD) can include monotherapy with either a selective serotonin reuptake inhibitor (SSRI) or a selective norepinephrine reuptake inhibitor (SNRI). SSRI/SNRI combination therapy has also proven to be effective. Recent research has investigated the efficacy of L-methylfolate, a prescription medical food for the dietary management of suboptimal L-methylfolate levels in patients with depression, for a major depressive episode (MDE).

Lawrence D. Ginsberg, MD, and colleagues conducted a retrospective chart review and studied 242 patients with a primary diagnosis of MDD with a single or recurrent MDE and Clinical Global Impression-Severity (CGI-S) score of >4. Patients were broken into two groups. The combination group (n=96) received an SSRI or an SNRI combined with l-methylfolate 7.5–15 mg/day. The monotherapy group (n=147) received either an SSRI or SNRI. The CGI-S was used as the primary outcome measure.

“I conducted the study after I used this medical food in many patients and started to see significant improvement without any additional adverse events,” Dr. Ginsberg wrote in an e-mail message. “I initially started using L-methylfolate in geriatric patients because this was the safest adjunctive therapy in a patient population that can least tolerate side effects. I next started to use this adjunctively in at-risk patients (those with medical conditions that deplete L-methylfolate, those on medications which deplete L-methylfolate, and those with lifestyle habits that deplete L-methylfolate).”

Ginsberg and colleagues found that combination therapy was more effective than monotherapy. Eighteen percent of patients in the combination group had a >2-point reduction in CGI-S scores. Only 7.4% of the monotherapy group showed this same reduction. On average, it took patients in the combination group 177 days to show major improvement. It took patients in the monotherapy group an average of 231 days to show the same amount of improvement, thus indicating a more rapid response for patients receiving combination therapy. Regarding the side effects, there was no statistical difference between both groups. When combined with an antidepressant, L-methylfolate is more effective in reducing the symptoms of MDD. It can be used as long-term therapy due to its high tolerability and fewer discontinuations when compared to the monotherapy group.

“I was not surprised that the outcomes were positive because this is what I suspected from my daily patient interactions. I was surprised by the magnitude of the differences between the SSRI/SNRI monotherapy and methylfolate plus SSRI/SNRI groups. Additionally, the methylfolate plus SSRI/SNRI group had medical comorbidity; despite this there were significant improvements over the monotherapy group,” Dr. Ginsberg wrote.

The researchers believe that more randomized, controlled trials on this subject are needed.

Funding for this research was supported by Pamlab. (APA 2010, Poster NR3-46) –Christopher Naccari


From → Pharmacotherapy

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