Approximately 70 percent of major depressive disorder (MDD) patients have a genetic abnormality that results in an imbalance of L-methylfolate2, the only form of folate that crosses the blood-brain barrier to help regulate neurotransmitters associated with depression.3
“Administering adjunctive agents such as L-methylfolate early in therapy as opposed to sequential drug use, or delaying a second agent, may represent a paradigm shift in the therapy of major depressive disorder,” said study author Lawrence D. Ginsberg, MD, of Red Oak Psychiatry in Houston. “Too often patients fail to respond to initial treatment and months go by before we are able to layer in additional medications. What we have found is that there are clear synergies between antidepressant drugs and L-methylfolate that result in better patient outcomes earlier in therapy.”
Major depressive disorder (MDD) is a chronic and recurrent disease affecting more than 18 million people in the United States, ranking it along with heart disease, cancer and diabetes among the nation’s most common ailments.4 Up to 50 percent of patients being treated for depression fail to reach remission.5
About the Study
Researchers performed a retrospective two-arm chart review of 242 adults, ages 18-70, with a primary diagnosis of MDD, a Clinical Global Impression - Severity (CGI-S) score of four (moderately ill) or five (markedly ill) and who were experiencing some degree of functional impairment. Charts of eligible patients were divided into a combination therapy arm of 95 patients administered selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) in combination with dietary management using 7.5-15 mg of L-methylfolate at initiation of therapy and a control arm of 147 patients using SSRI or SNRI monotherapy at therapy onset.
Data were recorded on patient characteristics before and after antidepressant therapy using the CGI-S Scale.
The primary outcome measure used in the study was a two-point decline in the CGI-S score, a seven-point scale developed by the National Institute of Mental Health. The CGI-S score is a clinician-determined measure that takes into account all available information, including knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function.
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). Among patients with greater functional impairment (CGI-S = 5), 40 percent of patients in the combination arm improved significantly within 60 days compared to 16.3 percent of patients in the control group (p= 0.02). The patients who received dietary management with L-methylfolate + SSRI/SNRI experienced a more rapid improvement than the monotherapy patients. 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).
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.1
|1. Ginsberg LD, Oubre A, Daoud Y. Innov Clin Neurosci. 2011;8(1):19-28.|
|2. Kelly C, McDonnell A, Johnston T, et al. J Psychopharmacol. 2004;18(4):567-71.|
|3. Stahl SM. CNS Spectrums. 2007;12(10):739-44.|
|4. The National Institute of Mental Health (NIMH). (n.d.).|
|5. Zajecka, John. J Clin Psychiatry. 2003;64[suppl 15]:7-12.|