BACKGROUND: Although major depressive disorder (MDD) is a treatable disease, the 
remission rates associated with antidepressant monotherapy are still far from 
optimal. Folate is an inexpensive, easily tolerated natural augmenting agent, 
which has been reported to improve medication treatment outcomes in patients 
with MDD.
OBJECTIVE: The aim of this study was to review the literature on the clinical 
utility of folate augmentation for patients with MDD. FOLATE AND DEPRESSION: 
Patients with depression have consistently been found to have lower levels of 
serum and red blood cell folate than normal or nondepressed psychiatric 
patients. Decreased folate levels have been associated with lowered response 
rates to standard antidepressant pharmacotherapy. Recent studies have shown that 
augmentation with a folate supplement increases medication response in both 
treatment-naïve and treatment-resistant depressed patients irrespective of 
whether there is folate deficiency.
CONCLUSIONS: Depressed patients with both low and normal folate levels may 
benefit from augmenting a primary antidepressant medication either initially, at 
the onset of treatment, or later after some degree of treatment resistance has 
been recognized.