Fortschr Neurol Psychiatr 2014; 82(2): 78-83
DOI: 10.1055/s-0033-1356123
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Folate in der Depressionsbehandlung

Folates in the Treatment of Depression
S. Erbe
1   Klinik für Psychiatrie, Psychotherapie und Psychosomatik, Martin Gropius Krankenhaus, I. Psychiatrische Klinik, Eberswalde
,
U. N. Pellert
2   Abteilung für Psychiatrie, Schlosspark-Klinik, Berlin
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
11. Februar 2014 (online)

Zusammenfassung

Die Depression ist eine bedeutsame und häufig wiederkehrende Erkrankung. Ein erster antidepressiv-pharmakologischer Behandlungsversuch führt leider nur bei ca. 30 % der Patienten zu einer Remission. Die meisten dieser behandelten Patienten sind nur Teil-Responder oder erfahren keine Besserung ihrer depressiven Symptomatik. Es findet sich immer mehr Evidenz dafür, dass ein Folatmangel sowohl die Entstehung einer depressiven Störung mitbedingen kann als auch mit einem schlechteren Behandlungsverlauf inklusive Therapieresistenz und einer schwereren Symptomatik assoziiert ist. Der folgende Übersichtsartikel fasst diese Evidenz zusammen und diskutiert einen möglichen klinischen Nutzen einer Substitution von L-Methylfolat und Folsäure in der Depressionsbehandlung.

Abstract

Depression is an important and often recurrent illness. An initial antidepressant trial is effective at achieving remission for about 30 % of patients when prescribed as monotherapy, with the majority of patients returning as partial or non-responders. Suboptimal serum and red blood cell folate levels have been associated with a poorer response to antidepressant therapy, a greater severity of symptoms, later onset of clinical improvement, and overall treatment resistance. This article reviews the evidence for L-methylfolate and folic acid as antidepressive agents in depression and discusses their clinical use.

 
  • Literatur

  • 1 Brönstrup A. Folat und Folsäure – Herausforderung für die Praxis. Ernährungs Umschau 2007; 9: 538-544
  • 2 Steinberg SE, Campbell CL, Hillman RS. Kinetics of the normal folate enterohepatic cycle. J Clin Invest 1979; 64: 83-88
  • 3 Halsted CH. The intestinal absorption of folates. Am J Clin Nutr 1979; 32: 846-855
  • 4 Stahl A, Heseker H. Folat – Physiologie, Vorkommen, Analytik, Referenzwerte und Versorgung in Deutschland. Ernährungs Umschau 2007; 6: 336-343
  • 5 Antony AC. Folate receptors. Annu Rev Nutr 1996; 16: 501-521
  • 6 Deutsche Gesellschaft für Ernährung. Referenzwerte für die Nährstoffzufuhr. D-A-CH Referenzwerte der DGE, ÖGE, SGE/SVE (23.06.2004). Im Internet: www.dge.de Stand: 03.09.2013
  • 7 Nationale Verzehrsstudie II (NVS II), herausgegeben vom Max-Rubner-Institut, Bundesforschungsinstitut für Ernährung und Lebensmittel, im Auftrag des Bundesministeriums für Ernährung, Landwirtschaft und Verbraucherschutz (2008). Im Internet: www.mri.bund.de ; Stand: 03.09.2013
  • 8 Stahl SM. Novel therapeutics for depression: l-methylfolate as a trimonamine modulator and antidepressant-augmenting agent. CNS Spectr 2007; 12: 739-744
  • 9 Stahl SM. L-methylfolate: a vitamin for your monoamines. J Clin Psychiatry 2008; 69: 1352-1353
  • 10 Paslakis G, Bleich S, Frieling H et al. Epigenetische Mechanismen der Depression. Nervenarzt 2011; 82: 1431-1439
  • 11 Peedicayil J. Role of epigenetics in pharmacotherapy, psychotherapy and nutritional management of mental disorders. J Clin Pharm Ther 2012; 37: 499-501
  • 12 Farah A. The role of l-methylfolate in depressive disorders. CNS spectr 2009; 14: 2-7
  • 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: 309-313
  • 14 Bottigleri T. Homocysteine and folate metabolism in depression. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 1103-1112
  • 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: 301-307
  • 16 Levitt AJ, Joffe RT. Folate, B12, and life course of depressive illness. Biol Psychiatry 1989; 25: 867-872
  • 17 Alpert JE, Fava M. Nutrition and depression: the role of folate. Nutr Rev 1997; 55: 145-149
  • 18 Wesson VA, Levitt AJ, Joffe RT. Change in folate status with antidepressant treatment. Psychiatry Res 1994; 53: 313-122
  • 19 Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol 2005; 19: 59-65
  • 20 Abou-Saleh MT, Coppen A. Serum and red blood cell folate in depression. Acta Psychiatr Scand 1989; 80: 78-82
  • 21 Reynolds EH, Preece JM, Bailey J et al. Folate deficiency in depressive illness. Br J Psychiatry 1970; 117: 287-292
  • 22 Folstein M, Liu T, Peter I et al. The homocysteine hypothesis of depression. Am J Psychiatry 2007; 164: 861-867
  • 23 Bottiglieri T, Hyland K, Laundry M et al. Folate deficiency, biopterin and monoamine metabolism in depression. Psychol Med 1992; 22: 871-876
  • 24 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: 457-494
  • 25 Hardeveld F, Spijker J, De Graaf R et al. Prevalence and predictors of recurrence of major depressive disorder in adult population. Acta Psychiatr Scand 2010; 122: 184-191
  • 26 Kang SS, Zhou J, Wong PW et al. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am j Hum Genet 1988; 43: 414-421
  • 27 Tan EC, Chong SA, Lim LC et al. Genetic analysis of thermolabile methylenetetrahydrofolate reductase variant in schizophrenia and mood disorders. Psychiatr Genet 2004; 14: 227-231
  • 28 Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: A HuGE review. Am J Epidemiol 2007; 165: 1-13
  • 29 Cortese C, Motti C. MTHFR gene polymorphism, homocysteine and cardiovascular disease. Public Health Nutr 2001; 4: 493-497
  • 30 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: 618-626
  • 31 Arinami T, Yamada N, Yamakawa-Kobayashi K et al. Methylenetetrahydrofolate reductase variant and schizophrenia/depression. Am J Med Genet 1997; 74: 526-528
  • 32 Hickie I, Scott E, Naismith S et al. Late-onset depression: genetic vascular and clinical contributions. Psychol Med 2001; 31: 1403-1412
  • 33 Kunugi H, Fukuda R, Hattori M et al. C677T polymorphism in methylenetetrahydrofolate reductase gene and psychosis variant. Mol Psychiatry 1998; 3: 435-437
  • 34 Reif A, Pfuhlmann B, Lesch KP. Homocysteine as well as methylenetetrahydrofolate reductase polymorphism are associated with affective psychosis. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 1162-1168
  • 35 Zintzaras E. C677T and A1298C methylenetetrahydrofolate reductase gene polymorphism in schizophrenia, bipolar disorder and depression: a meta-analysis of genetic association studies. Psych Genet 2006; 16: 105-115
  • 36 Godfrey PS, Toone BK, Carney MW et al. Enhancement of recovery from psychiatric illness by methylfolate. Lancet 1990; 336: 392-395
  • 37 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: 63-71
  • 38 Peerbooms OLJ, van Os J, Drukker M et al. Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: Evidence for a common genetic vulnerability?. Brain Behav Immun 2011; 25: 1530-1543
  • 39 Crellin R, Bottiglieri T, Reynolds EH. Folates and psychiatric disorders: clinical potential. Drugs 1993; 45: 623-636
  • 40 Leeming RJ. Enhancement of recovery from psychiatric illness by methylfolate. Lancet 1990; 336: 953-954
  • 41 Procter A. Enhancement of recovery from psychiatric illness by methylfolate. Br J Psychiatry 1991; 159: 271-272
  • 42 Anderson D, Wilkinson A, Abou-Saleh M et al. Enhancement of recovery from psychiatric illness by methylfolate. Br J Psychiatry 1992; 160: 130
  • 43 Wing YK, Lee S. Methylfolate and psychiatric illness. Br J Psychiatry 1992; 160: 714-715
  • 44 Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Disord 2000; 60: 121-130
  • 45 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: 145-152
  • 46 Coppen A, Chaudhry SSC. Folic acid enhances lithium prophylaxis. J Affect Disord 1986; 10: 9-13
  • 47 Fava M, Evins AE, Dorer DJ et al. The problem of the placebo response in clinical trials for psychiatric disorders: culprits, possible remedies, and a novel study design approach. Psychother Psychosom 2003; 72: 115-127
  • 48 Papakostas GI, Shelton RC, Zajecka JM et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry 2012; 169: 1267-1274
  • 49 Bauer M, Dopfmer S. Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. J Clin Psychopharmacol 1999; 19: 427-434
  • 50 Nelson JC, Papakostas GI. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry 2009; 166: 980-991
  • 51 Bauer M, Adli M, Bschor T et al. Lithium’s emerging role in the treatment of refractory major depressive episodes: augmentation of antidepressants. Neuropsychobiology 2010; 62: 36-42
  • 52 Erbe S, Gutwinski S, Bschor T. Augmentation von Antidepressiva mit atypischen Antipsychotika bei Nonresponse auf eine Antidepressiva-Monotherapie. Eine systematische Übersichtsarbeit randomisierter placebokontrollierter Studien bei unipolarer nicht wahnhafter Depression. Psychiat Prax 2012; 39: 57-63
  • 53 Papakostas GI, Cassiello CF, Iovieno N. Folates and s-adenosylmethionine for major depressive disorder. Can J Psychiatry 2012; 57: 406-413
  • 54 Shelton RC, Manning JS, Barrentine LW et al. Assessing effects of l-methylfolate in depression management: results of a real-world patient experience trial. Prim Care Companion CNS Disord 2013; 15 DOI: 10.4088/PCC.13m01520.
  • 55 Mischoulon D, Fava M, Stahl SM. In reply to: Frankenburg FR. Folate supplementation: is it safe and effective [letter]?. J Clin Psychiatry 2009; 70: 767-769
  • 56 Greenberg JA, Bell SJ. Multivitamin supplementation during pregnancy: emphasis on folic acid and l-methylfolate. Rev Obstet Gynecol 2011; 4: 126-127
  • 57 DGPPN, BÄK, KBV, AWMF, AkdÄ, BPtK, BApK, DAGSHG, DEGAM, DGPM, DGPs, DGRW (Hrsg) für die Leitliniengruppe Unipolare Depression*. S3-Leitlinie/Nationale Versorgungsleitlinie Unipolare Depression. 1. Aufl. Berlin, Düsseldorf: DGPPN, ÄZQ, AWMF. Internet: 2009 www.dgppn.dewww.versorgungsleitlinien.de www.awmf-leitlinien.de (*Organisationen, die in der Leitliniengruppe kooperierten: DGPPN, BÄK, KBV, AWMF, AkdÄ, BPtK, BApK, DAGSHG, DEGAM, DGPM, DGPs, DGRW, BDK, BDP, BPM, BVDN, BVDP, BVVP, CPKA, DÄVT, DFT, DGGPP, DGPT, DGVT, DPG, DPV, DPtV, DVT, Deutscher Hausärzteverband, GwG, KND)
  • 58 American Psychiatric Association (APA). Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. Arlington (VA): American Psychiatric Association (APA); 2010: 152 [1170 references]