Combining L-methylfolate with an SSRI or an SNRI proved more effective than monotherapy at treatment initiation in a study of 242 patients with major depressive disorder published in Innovations in Clinical Neuroscience.
When they added 7.5 mg or 15 mg of L-methylfolate to another antidepressant, Dr. Lawrence D. Ginsberg and his associates reported improvement in patients’ symptoms and a reduction in Clinical Global Impression-Severity (CGI-S) scores, in which 1 is "normal" and 7 is "extremely ill."
In the group of 95 patients on combination treatment, 18.5% saw at least a two-point reduction in CGI-S scores during a 60-day period. In contrast, only 7% saw the same reduction in the group of 147 patients on monotherapy of either a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI), reported Dr. Ginsberg, a Houston psychiatrist who is in private practice.
Patients on the L-methylfolate combo also improved more rapidly. Their median time to achieve at least a two-point reduction on the CGI-S scale was 177 days, compared with 231 days for those on the monotherapy group. The team did not find any side effects from the addition of L-methylfolate (Innov. Clin. Neurosci. 2011;8:19-28).
The patients were aged 18-70 years, and each one began with a CGI-S score of 4-5. Although the results built upon those of previous investigations on the effective use of folate when treating major depressive episodes, this single-site study limited itself to retrospective chart analysis. The team did not measure patients’ baseline folate levels.
In an interview, Dr. Ginsberg explained his reasoning in deciding who got the monotherapy and who received the L-methylfolate-antidepressant combination. "If I felt it was in the best interests of an individual patient, then I prescribed L-methylfolate," he said.
The use of L-methylfolate is part of a "paradigm shift" over the last 5 years toward initial combination therapy, said Dr. Stephen M. Stahl, adjunct psychiatry professor at the University of California, San Diego. He added, however, that psychiatrists have tried multiple therapies at treatment initiation for almost a decade now.
Dr. Stahl, whose work is cited in Dr. Ginsberg’s study, said that whereas the classical approach is to try adjunctive therapy after monotherapy fails, the norm in cancer and HIV/AIDS treatment is to begin with three or four drugs. "Depression is moving in that direction," he said in an interview. Dr. Stahl, who is also chairman of the Neuroscience Education Institute, expressed doubts about the Ginsberg study design. "This is more of an interesting hypothesis-generating study than a hypothesis-confirming study," he said. Because the study was neither randomized nor controlled, he said it was "not a completely objective comparison" of the test group and the control group.
Dr. Ginsberg’s study is by no means isolated. Dr. Maurizio Fava, psychiatry professor at Harvard Medical School, Boston, presented a similar study in a poster at the American College of Neuropsychopharmacology’s annual meeting in December, but these results have not yet been published in a peer-reviewed journal.
Dr. Stahl considers Dr. Fava’s results to be more convincing because of that study’s randomized controlled design. "Taken in the context of the Fava study, the Ginsberg study is more interesting," he said.
However, Dr. Stahl acknowledged that such a comparison is difficult because, although Dr. Fava tested the effectiveness of adding L-methylfolate to treatment with SSRIs, his study does not focus on treatment initiation.
The Ginsberg study received funding from Pamlab, which manufactures the medical food L-methylfolate under the brand name Deplin. Dr. Ginsberg also reported his work as a speaker for Pamlab and as a consultant for various other pharmaceutical companies. Dr. Stahl disclosed that he has done consulting for Pamlab. Dr. Fava also has consulted for and received funding from Pamlab.