From the FDA Drug Label
L-METHYLFOLATE CALCIUM Tablets is a medical food dispensed by prescription for the clinical dietary management of the metabolic imbalances associated with depression and schizophrenia. 5-MTHF has been shown to enhance antidepressant effects of known antidepressants.
The evidence for Deplin (L-methylfolate) from double-blind studies for treating depression is not directly mentioned in the provided drug labels. However, it is stated that L-methylfolate has been shown to enhance antidepressant effects of known antidepressants 1.
- The labels do not provide specific details on double-blind studies for Deplin in treating depression.
- Caution is recommended in patients with a history of bipolar illness, as L-methylfolate may enhance antidepressant effects and potentially precipitate a mixed/manic episode in patients at risk for bipolar disorder 1.
From the Research
L-methylfolate (Deplin) has modest evidence from double-blind studies for treating depression, primarily as an adjunctive therapy rather than as monotherapy, with the most recent and highest quality study suggesting its potential benefits in specific subgroups of patients with major depressive disorder (2).
Key Findings
- Several randomized controlled trials have shown that L-methylfolate at doses of 15mg daily can improve response rates when added to antidepressants in patients with major depressive disorder who have not adequately responded to antidepressant therapy alone (3,4).
- The benefits of L-methylfolate appear more pronounced in specific subgroups, particularly patients with genetic variations affecting folate metabolism (such as those with MTHFR polymorphisms) and those with markers of inflammation (2).
- The mechanism involves L-methylfolate's role as a critical cofactor in the synthesis of neurotransmitters including serotonin, norepinephrine, and dopamine (5).
Clinical Implications
- L-methylfolate is generally well-tolerated with minimal side effects, making it a reasonable augmentation strategy for patients with treatment-resistant depression, especially those with potential folate metabolism issues (3,2).
- However, the overall strength of evidence remains limited by relatively small sample sizes, varying study designs, and inconsistent results across different patient populations (6).
Recommendation
- Based on the most recent and highest quality study, L-methylfolate (Deplin) may be considered as an adjunctive therapy for patients with major depressive disorder who have not adequately responded to antidepressant therapy alone, particularly in those with genetic variations affecting folate metabolism or markers of inflammation (2).