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The Role of L-Methylfolate in Depressive Disorders

Published online by Cambridge University Press:  07 November 2014

Andrew Farah
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Major depressive disorder (MDD) is a debilitating illness affecting 7% to 12% of men and 20% to 25% of women. It is usually a recurrent illness, with up to 30% of patients experiencing a depressive episode lasting over 2 years. Depression may also increase the morbidity and mortality of numerous medical conditions, such as cardiac disease, myocardial infarction, chronic pain, diabetes, cerebrovascular events, and respiratory illnesses. The goal of antidepressant therapy is to achieve full remission and functional recovery, and continuing treatment beyond the acute phase is usually necessary to maintain remission. In contrast with full remission, individuals who experience residual symptoms, however mild, have a higher chance of experiencing one or more additional episodes.

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Type
Expert Review Supplement
Information
CNS Spectrums , Volume 14 , Issue S2: The Role of L-Methylfolate in Depressive Disorders , January 2009 , pp. 2 - 7
Copyright
Copyright © Cambridge University Press 2009

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References

1.Depression Guideline Panel. Clinical Practice Guideline Number 5: Depression in Primary Care Volume 1: Detection and Diagnosis. Rockville, Md: HHS; 1993. AHCR publication 93–0550.Google Scholar
2.Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.Google Scholar
3.Keller, MB, Boland, RJ. Implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression. Biol Psychiatry. 1998;44(5):348–360.CrossRefGoogle ScholarPubMed
4.Carney, RM, Saunders, RD, Freedland, KE, et al. Association of depression with reduced heart rate variability in coronary artery disease. Am J Cardiol. 1995;76(8):562–564CrossRefGoogle ScholarPubMed
5.Stein, PK, Carney, RM, Freedland, KE, et al. Severe depression is associated with markedly reduced heart rate variability in patients with stable coronary heart disease. J Psychosom Res. 2000;48(4–5):493–500.CrossRefGoogle ScholarPubMed
6.Penninx, BW, Beekman, AT, Honig, A, et al. Depression and cardiac mortality: results from a community-based longitudinal study. Arch Gen Psychiatry. 2001;58(3):221–227.CrossRefGoogle ScholarPubMed
7.Frasure-Smith, N, Lésperance, F, Talajic, M. Depression following myocardial infarction: impact on 6-month survival. JAMA. 1993;270(15):1819–1825.CrossRefGoogle ScholarPubMed
8.Bush, DE, Ziegelstein, RC, Tayback, M, et al. Even minimal symptoms of depression increase mortality risk after acute myocardial infarction. Am J Cardiol. 2001;88(4):337–341.CrossRefGoogle ScholarPubMed
9.Lésperance, F, Frasure-Smith, N, Talajic, M, Bourassa, MG. Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infarction. Circulation. 2002;105(9):1049–1053.CrossRefGoogle ScholarPubMed
10.Fishbain, DA, Cutler, R, Rosomoff, HL, Rosomoff, RS. Chronic pain-associated depression: antecedent or consequence of pain? a review. Clin J Pain. 1997;13(2)116–137.CrossRefGoogle ScholarPubMed
11.Egede, LE, Zheng, D, Simpson, K. Comorbid depression is associated with increased health care use and expenditures in individuals with diabetes. Diabetes Care. 2002;25(3):464–470.CrossRefGoogle ScholarPubMed
12.Fava, M, Rush, AJ, Trivedi, MH, et al. Background and rationale for the Sequenced treatment alternatives to relieve depression (STAR*D) study. Psych Clin North Amer. 2003;26(2):457–494.CrossRefGoogle ScholarPubMed
13.Alpert, M, Silva, RR, Pouget, ER. Prediction of treatment response in geriatric depression from baseline folate level: interaction with an SSRI or a tricyclic antidepressant. J Clin Psychopharmacol. 2003;23(3):309–313.CrossRefGoogle ScholarPubMed
14.Bottigleri, T. Homocysteine and folate metabolism in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(7):1103–1112CrossRefGoogle Scholar
15.Papakostas, GI, Iosifescu, DV, Renshaw, PF, et al. Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II). Psychiatry Res. 2005;140(3):301–307.CrossRefGoogle ScholarPubMed
16.Levitt, AJ, Joffe, RT. Folate, B12, and life course of depressive illness. Biol Psychiatry. 1989;25(7):867–872.CrossRefGoogle ScholarPubMed
17.Alpert, JE, Fava, M. Nutrition and depression: the role of folate. Nutr Rev. 1997;55(5):145–149.CrossRefGoogle ScholarPubMed
18.Wesson, VA, Levitt, AJ, Joffe, RT. Change in folate status with antidepressant treatment. Psychiatry Res. 1994;53(3):313–122.CrossRefGoogle ScholarPubMed
19.Coppen, A, Bolander-Gouaille, C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol. 2005;19(1):59–65.CrossRefGoogle ScholarPubMed
20.Abou-Saleh, MT, Coppen, A. Serum and red blood cell folate in depression. Acta Psychiatr Scand. 1989;80(1):78–82.CrossRefGoogle ScholarPubMed
21.Botto, LD, Yang, Q. 5,10-methylenetetrahydofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. 2000;151(9):862–877.CrossRefGoogle Scholar
22.Bailey, LB, Gregory, JF 3rd. Polymorphisms of MTHFR and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr. 1999;129(5):919–922.CrossRefGoogle ScholarPubMed
23.Bjelland, I, Tell, GS, Vollset, SE, et al. Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003;60(6):618–626.CrossRefGoogle Scholar
24.Arinami, T, Yamada, N, Yamakawa-Kobayashi, K, et al. Methylenetetrahydrofolate reductase variant and schizophrenia/depression. Am J Med Genet. 1997;74(5):526–528.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
25.Procopciuc, LM, Jebeleanu, GH, Fodoreanu, L, Crisan, C, et al. C677T MTHFR Polymorphism and Psychiatric Diseases Schizophrenia-like Psychosis and Depression in Romanian Patients. In: 60th Annual Meeting of the Society of Biological Psychiatry. May 19–21, 2005, Atlanta, Georgia. Poster P86.Google Scholar
26.Kelly, CB, McDonnell, AP, Johnston, TG, et al. The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol. 2004;18(4):567–571.CrossRefGoogle ScholarPubMed
27.Paykel, ES, Ramana, R, Cooper, Z, et al. Residual symptoms after remission: an important outcome in depression. Psychol Med. 1995;25(6):1171–1180.CrossRefGoogle ScholarPubMed
28.Judd, LL, Akiskal, HS, Maser, JD, et al. A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Arch Gen Psychiatry. 1998;55(8):694–700.CrossRefGoogle ScholarPubMed
29.Judd, LL, Akiskal, HS, Zeller, PJ, et al. Psychosocial disability during the long-term course of unipolar major depressive disorder. Arch Gen Psychiatry. 2000;57(4):375–380.CrossRefGoogle ScholarPubMed
30.McGrath, PJ, Stewart, JW, Fava, M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1531–1541.CrossRefGoogle ScholarPubMed
31.Rush, AJ, Trivedi, MH, Wisniewski, SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905–1917.CrossRefGoogle ScholarPubMed
32.Nierenberg, AA, Fava, M, Trivedi, MH, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1519–1530.CrossRefGoogle Scholar
33.Trivedi, MH, Fava, M, Marangell, LB, et al. Use of treatment algorithms for depression. J Clin Psychiatry. 2006;67(9):1458–1465.CrossRefGoogle ScholarPubMed
34.Trivedi, MH, Fava, M, Wisniewski, SR, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354(12):1243–1252.CrossRefGoogle ScholarPubMed
35.Trivedi, MH, Rush, AJ, Wisniewski, SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163(1):28–40.CrossRefGoogle ScholarPubMed
36.Morris, MS, Fava, M, Jacques, PF, et al. Depression and folate status in the US Population. Psychother Psychosom. 2003;72(2):80–87.CrossRefGoogle ScholarPubMed
37.Obeid, R, Kostopoulos, P, Knapp, JP, et al. Biomarkers of folate and vitamin B12 are related in blood and cerebrospinal fluid. Clin Chem. 2007;53(2):326–333.CrossRefGoogle ScholarPubMed
38.Alpert, JE, Fava, M. Nutrition and depression: the role of folate. Nutr Rev. 1997;55(5):145–149.CrossRefGoogle ScholarPubMed
39.Coppen, A, Swade, C, Jones, SA, et al. Depression and tetrahydrobiopterin: the folate connection. J Affect Disord. 1989;16(2–3):103–107CrossRefGoogle ScholarPubMed
40.Abou-Saleh, MT, Coppen, A. The biology of folate in depression: implications for nutritional hypotheses of the psychoses. J Psychiatr Res. 1986;20(2):91–101.CrossRefGoogle ScholarPubMed
41.Papakostas, GI, Petersen, T, Mischoulon, D, et al. Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression. J Clin Psych. 2004;65:1090–1095.CrossRefGoogle ScholarPubMed
42.Papakostas, GI, Petersen, T, Mischoulon, D, et al. Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 2: predictors of relapse during the continuation phase of pharmacotherapy. J Clin Psych. 2004;65:1096–1098.CrossRefGoogle ScholarPubMed
43.Gilbody, S, Lewis, S, Lightfoot, T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphism and psychiatric disorders: a HuGE review. Am J Epidemiology. 2007;165:1–13.CrossRefGoogle ScholarPubMed
44.Coppen, A, Bailey, J. Enhancement of the antidepressant action of fluoxetine by folic acid: a ramdomised placebo controlled trial. J Affect Disord. 2000;60:121–130.CrossRefGoogle Scholar
45.Coppen, A, Chaudhry, C, Swade, C. Folic acid enhances lithium prophylaxis. J Affect Disord. 1986;10:9–13.CrossRefGoogle ScholarPubMed
46.Carney, NW, Chary, TK, Laundy, M, et al. Red cell folate concentrations in psychiatric patients. J Affect Disord. 1990;19:207–213CrossRefGoogle ScholarPubMed
47.Reynolds, EH, Preece, JM, Bailey, J, Coppen, A. Folate deficiency in depressive illness. Br J Psychiatry. 1970;117:287–292.CrossRefGoogle ScholarPubMed
48.Alpert, M, Silva, RR, Pouget, ER. Prediction of treatment response in geriatric depression from baseline folate level: interaction with an SSRI or a tricyclic antidepressant. J Clin Psychopharmacology. 2003;23(3):309–13.CrossRefGoogle ScholarPubMed
49.Stahl, SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed.New York: Cambridge University Press; 2008:625–632Google Scholar
50.Stahl, SM. Novel therapies for depression: l-methylfolate as a trimonoamine modulator and antidepressant agent. CNS Spectr. 2007;12;739–744.CrossRefGoogle Scholar
51.Bolander-Gouaille, C, Bottiglieri, T. Clinical impact of enzyme defects. Homocysteine Related Vitamins and Neuropsychiatric Disorders. New York, NY; Springer: 2004;151–162.Google Scholar
52.Tan, EC, Chong, SA, Lim, LC, et al. Genetic analysis of thermolabile methylenetertrahydrofoalte reductase variant in schizophrenia and mood disorders. Psychiatr Genet. 2004;14:227–231.CrossRefGoogle ScholarPubMed
53.Bjelland, I, Tell, GS, Vollset, SE, et al. Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003;60(6):618–626.CrossRefGoogle Scholar
54.Arinami, T, Yamada, N, Yamakawa-Kobayashi, K, et al. Methylenetetrahydrofolate reductase variant and schizophrenia/depression. Am J Med Genet. 1997;74:526–528.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
55.Hickie, I, Scott, E, Naismith, S, et al. Late-onset depression: genetic vascular and clinical contributions. Psychol Med. 2001:31;1403–1412.CrossRefGoogle ScholarPubMed
56.Kunugi, H, Fukuda, R, Hattori, M, et al. C677T polymorphism in methylenetetrahydrofolate reductase gene and psychosis variant. Mol Psychiatry. 1998;3:435–437.CrossRefGoogle Scholar
57.Reif, A, Pfuhlmann, B, Lesch, KP. Homocysteine as well as methylenetertrahydrofoalte reductase polymorphism are associated with affective psychosis. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:1162–1168.CrossRefGoogle Scholar
58.Zintzaras, E. C677T and A1298C methylenetertrahydrofoalte reductase gene polymorphism in schizophrenia, bipolar disorder and depression: a meta-anylsis of genetic association studies. Psych Genet. 20067;16:105–115.CrossRefGoogle Scholar
59.Godfrey, PS, Toone, BK, Carney, MW, et al. Enhancement of recovery from psychiatric illness by methylfolate. Lancet. 1990;336(8712):392–395.CrossRefGoogle ScholarPubMed
60.Passeri, M, Cucinotta, D, Abate, G, et al. Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Aging (Milano). 1993;5(1):63–71.Google ScholarPubMed
61.Guaraldi, GP, Fava, M, Mazzi, F, la Greca, P. An open trial of methyltetrahydrofolate in elderly depressed patients. Ann Clin Psychiatry. 1993;5:101–105.CrossRefGoogle ScholarPubMed
62.Di Palma, C, Urani, R, Agricola, R, et al. Is methylfolate effective in relieving major depression in chronic alcoholics? A hypothesis of treatment. Curr Ther Res Clin Exp. 1994;55(5):559–568.CrossRefGoogle Scholar
63.Alpert, JE, Mischoulon, D, Rubenstein, GE, et al. Folinic acid as an adjunctive treatment for SSRI-refractory depression. Ann Clin Psych 2002:14:33–38.CrossRefGoogle ScholarPubMed
64.Yang, QH, Botto, LD, Gallagher, M, et al. Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the US: findings from the third national health and nutrition examination survey DNA bank. Am J Clin Nutr. 2008;88(1):232–246.CrossRefGoogle ScholarPubMed
65.Folstein, M, Liu, T, Peter, I, et al. The homocysteine hypothesis of depression. Am J Psychiatry. 2007;164(6):861–867.CrossRefGoogle ScholarPubMed
66.Roffman, JL, Weiss, AP, Purcell, S, et al. Contribution of methylenetertrahydrofoalte reductase (MTHFR) polymorphism to negative symptoms in schizophrenia. Biol Psychiatry. 2008;63:42–48.CrossRefGoogle ScholarPubMed
67. Deplin [package insert]. Covington, LA: Pamlab; 2008.Google Scholar
68.Farah, A. Atypicality of atypical antipsychotics. Prim Care Companion J Clin Psychiatry. 2005;7:268–274.Google ScholarPubMed
69.Troen, AM, Mitchell, B, Sorensen, B, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr. 2006;136:189–194.CrossRefGoogle ScholarPubMed
70.Hunter, R, Barnes, J. Toxicity of folic acid given in pharmacological doses to healthy volunteers. Lancet. 1(7637):61–63.Google Scholar
71.Aisen, PS, Schneider, LS, Sano, M, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300(15):1774–1783.CrossRefGoogle ScholarPubMed
72.Resler, G, Lavie, R, Campos, J, et al. Effect of folic acid combined with fluoxetine in patients with major depression on plasma homocysteine and vitamin B12, and serotonin levels in lymphocytes. Neuroimmunomodulation. 2008;15(3):145–152.CrossRefGoogle ScholarPubMed