Editorial Folic acid and the treatment of depression B Mohammed T. Abou-Saleh a, 4 , Alec Coppen b a St George’s Hospital, University of London, Crammer Terrace, London SW17 0RE, UK b MRC Neuropsychiatry Research Laboratory, Epsom, Surrey KT18 5JL, UK Received 20 June 2006 Abstract Reduced plasma, serum, or red blood cell folate is commonly found in major depressive illnesses. Supplementing antidepressant medication with folic acid enhances the therapeutic effect. Although more work is required to confirm these beneficial results, it is suggested that, meanwhile, 2 mg of folic acid should be given during the acute, continuation, and maintenance treatment of depression. D 2006 Elsevier Inc. All rights reserved. Keywords: Depression; Folic acid; Treatment; Vascular disease Introduction Numerous studies have reported that patients with major depression have low plasma, serum, or red blood cell folate concentration [1]. We have previously found that both plasma and red blood cell folate concentrations were on average about 24% lower in drug-free, acutely ill depressed patients than in normal control subjects and that lower serum folate concentrations were associated with greater severity of depression [2]. An earlier study by Reynolds et al. [3] showed that the therapeutic outcome following antidepressant or electroconvulsive therapy was inferior if the plasma folate was low. High plasma folate levels are also important for the continuation treatment of depression. Papakostas et al. [4] followed up 71 outpatients with remitted major depression for 28 weeks who were treated with fluoxetine and found that the relapse rate of patients with low folate was 42.9% compared with the 3.2% relapse rate of patients with higher folate levels. Coppen and Abou- Saleh [5] reported that patients with higher plasma folate attending a lithium clinic had significantly lower affective morbidity over 2 years than patients with lower plasma folate. Papakostas et al. [6] have also reported that, in patients who failed to respond to fluoxetine and who received augmentation therapy with lithium or desipramine, low folate was associated with a lower response rate (7.1%) than in those with normal folate levels (44.7%). Community studies have also shown a link between low serum folate and depressive symptoms. Sachdev et al. [7] examined the relationship between folic acid and depression in a community sample of 412 persons between 60 and 64 years of age and found that low serum folate and high homocysteine were associated with depressive symptoms. A further important finding is the association between coronary artery disease (CAD) and depression [8]. Surveys have shown that patients who develop depression have an increased risk of CAD and that patients with CAD who are depressed have a worse outlook than nondepressed patients. CAD and depression show a common pathology in the form of low serum folate [9]. Folate is a major determinant of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional 0022-3999/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.jpsychores.2006.07.007 B Declaration of interest: Alec Coppen possesses a patent for medication, including that for an antidepressant and folic acid, whereas Mohammed T. Abou-Saleh has none. 4 Corresponding author. St George’s Hospital, University of London, Crammer Terrace, London SW17 0RE, UK. E-mail addresses: mabousal@sgul.ac.uk (M.T. Abou-Saleh)8 acoppen@globalnet.co.uk (A. Coppen). Journal of Psychosomatic Research 61 (2006) 285 – 287