Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial

Folate Augmentation of Treatment – Evaluation for Depression (FolATED): randomised trial and economic evaluation

“…Only two RCTs were identified (combined n = 151), both of which suggest possible beneficial effects of folate augmentation. 65,66 Two further small trials have given contradictory results. One study, 67 with a clinical sample of 42 patients with major depressive disorder, reported that 10 mg of escitalopram (Cipralex ® , Lundbeck) alone produced greater improvement than the combination of escitalopram and folic acid (2.5 mg/day).…”

“…50 Hence our updated review analysed three trials -FolATED with 440 analysable participants, Coppen and Bailey with 100, 65 and Godfrey et al with 24. 66 As the primary analysis of the much larger FolATED trial favours the placebo (Figure 18), our updated review reverses the findings of the Cochrane review.…”

“…However the supporting evidence is little more than biochemical theory and two small trials. 65,66 Indeed the authors of the current Cochrane systematic review concluded that there was limited evidence that adding folate to ADM was helpful, and recommended a trial like FolATED to test this hypothesis thoroughly. 50 …”

Combining Antidepressant Therapies From the Initiation of Treatment: A Paradigm Shift for Major Depression

“…Three randomized controlled trials 11,12,14 have shown superior efficacy of antidepressant and folate/methylfolate combinations from initiation of therapy compared to antidepressants alone.…”

“…J Clin Psychiatry 70:11, November 2009 1494 than in the antidepressant monotherapy group. A second study 12 randomized patients with major depression to the SSRI fluoxetine + 0.5 mg of folate or to fluoxetine alone. Not surprisingly, plasma folate levels rose, especially in women, but plasma homocysteine levels 13 (which l-methylfolate converts into methionine and then S-adenosylmethionine) declined only in women.…”