Folic acid may have a role in managing depression for some people when taken along with prescription antidepressants. Still, more research is needed to understand this effect and what form of supplemental folate may be most effective.
Mechanistically, folate is involved in the generation of S-adenosylmethionine (SAMe), a compound that is important for synthesizing neurotransmitters like dopamine, norepinephrine, and serotonin. Additionally, low folate levels may lead to high homocysteine, which has been positively correlated with depression symptom severity.[1] Although research has generally been mixed regarding whether depression is associated with reduced folate status,[2][3][1] folate deficiency has been associated with an increased risk of depression and longer, more severe episodes of depression.[1]
Folic acid taken along with antidepressant medications, specifically selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs), may reduce depression symptoms and increase rates of remission compared to antidepressants alone.[4][5][6] However, supplementing with L-methylfolate (an active form of folate that can cross the blood-brain barrier) may be more effective than folic acid.[7][8]
Importantly, there is insufficient research to suggest that folic acid or L-methylfolate taken alone is effective for depression or to determine whether folic acid or L-methylfolate are effective when taken with other types of antidepressants (e.g., tricyclic antidepressants).