Methylfolate for Depression

A 2014 study found that 15mg of L-methylfolate daily was significantly more effective at treating selective serotonin reuptake inhibitor (SSRI medication) resistant depression than placebo over 60 days.

Another 2014 study did not show any benefit from adding 5mg of folic acid (not methylated) vs placebo to anti-depressant medication over 12 weeks in patients with moderate to severe depression. High folic acid intake may mask vitamin B12 deficiency, affect medication levels, or have other side effects.

Papakostas GI, Shelton RC, Zajecka JM, Bottiglieri T, Roffman J, Cassiello C, Stahl SM, Fava M. Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial. J Clin Psychiatry. 2014 Aug;75(8):855-63. doi: 10.4088/JCP.13m08947. PMID: 24813065.

Bedson E, Bell D, Carr D, Carter B, Hughes D, Jorgensen A, Lewis H, Lloyd K, McCaddon A, Moat S, Pink J, Pirmohamed M, Roberts S, Russell I, Sylvestre Y, Tranter R, Whitaker R, Wilkinson C, Williams N. Folate Augmentation of Treatment--Evaluation for Depression (FolATED): randomised trial and economic evaluation. Health Technol Assess. 2014 Jul;18(48):vii-viii, 1-159. doi: 10.3310/hta18480. PMID: 25052890; PMCID: PMC4780991.

National Institutes of Health. “Office of Dietary Supplements - Folate.” Nih.gov, National Institutes of Health, 2022, ods.od.nih.gov/factsheets/Folate-HealthProfessional/.