Folate

Folate supplementation may enhance the antidepressant effect of medication. The article recommends starting L-methylfolate at 400–800 mcg and titrating cautiously. Folic acid is synthetic and must be converted to L-methylfolate before it can act in the brain. L-methylfolate is described as the only folate form directly active in the central nervous system. Low folate status is associated with higher depression rates and poorer antidepressant response. High-dose L-methylfolate has evidence for antidepressant augmentation but may cause anxiety and agitation.