Supplementation with
folate may help reduce depressive symptoms.
Folate, a naturally occurring
B vitamin, is needed in the brain for the synthesis of
norepinephrine,
serotonin, and
dopamine. Three forms of
folate are commonly used:
folic acid,
5-methyltetrahydrofolate (5-MTHF) (also known as methylfolate and
L-methylfolate), and
folinic acid. Some forms may be more bioavailable than others in patients with a genetic polymorphism and in those who take particular medications or use alcohol.
Folic acid augmentation in depressed patients may reduce residual symptoms. The 5-MTHF formulation indicated efficacy as adjunctive
therapy or monotherapy in reducing depressive symptoms in patients with normal and low
folate levels, improving cognitive function and reducing depressive symptoms in elderly patients with
dementia and
folate deficiency, and reducing depressive and
somatic symptoms in patients with depression and
alcoholism. Adjunctive
folinic acid reduced depressive symptoms in patients who were partially responsive or nonresponsive to a
selective serotonin reuptake inhibitor. Evidence for the efficacy of
folate in improving
cognitive symptoms is equivocal, but most studies used
folic acid. Although the studies reviewed have limitations and, historically, concerns have been raised about the role of
folate in increasing
cancer risk, masking B(12) deficiency, and worsening depressive symptoms,
folate is generally well tolerated, and 5-MTHF may be less likely to incur some of these risks. Several forms of
folate appear to be safe and efficacious in some individuals with
major depressive disorder, but more information is needed about dosage and populations most suited to
folate therapy.