Evaluation of antidepressant activity of l-methylfolate per se and its interaction with escitalopram in mice

Authors

  • Sapna A. More Department of Pharmacology, M.G.M. Medical College, Indore, Madhya Pradesh, India
  • Pooja S. Mishra Department of Pharmacology, M.G.M. Medical College, Indore, Madhya Pradesh, India
  • Ashutosh Tiwari Department of Pharmacology, M.G.M. Medical College, Indore, Madhya Pradesh, India
  • Savita Vyas Department of Pharmacology, M.G.M. Medical College, Indore, Madhya Pradesh, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20183478

Keywords:

Escitalopram, Forced swimming test, L-methylfolate, Major depressive disorder, Tail suspension test

Abstract

Background: Depression is a worldwide illness in the current population. Low levels of L-methylfolate are linked to depression. Present study evaluates the anti-depressive activity of acute and chronic administration of L-methylfolate per se in forced swimming test (FST) and tail suspension test (TST) and its interaction with escitalopram in albino mice.

Methods: For this 30 swiss albino mice were divided randomly into five groups (n=6) as group I (control,10ml/Kg, p.o) - 2% suspension of gum acacia, group II - escitalopram suspension (10mg/kg, p.o), group III- L-methylfolate suspension (3mg/kg, p.o), group IV- L-methylfolate (3mg/kg, p.o) plus escitalopram (5mg/kg, p.o), group V- L-methylfolate(3mg/kg, p.o) plus escitalopram(10mg/kg, p.o), for forced swimming test. In tail suspension test again, mice were divided in five groups as above except that the dose of L-methylfolate was reduced to 1.25mg/kg. The pharmacologically validated models forced swimming test and tail suspension test were performed in mice to evaluate acute and chronic antidepressant activity of L-methylfolate and its combination with escitalopram respectively, after performing an acute toxicity study.

Results: L-methylfolate and L-methylfolate plus escitalopram (10mg/Kg and 5mg/Kg, p.o) showed acute and chronic antidepressant activity in albino mice in FST and TST respectively. In human L-methylfolate is only active form of folic acid that readily crosses the blood brain barrier and utilized by the CNS. It regulates the bioavailability of critical cofactor BH4, required by enzymes synthesizing monoamines whose deficiency leads to depression.

Conclusions: Hence, this study suggests antidepresant activity of L-methylfolate per se and as adjuvant with escitalopram when initiated from initiation of antidepressant therapy. Also, L-methylfolate opens the possibility of reducing the dose of antidepressant when used as adjuvant.

References

American Psychiatric Association. Diagnostic and statistics manual of mental disorders: DSM-I, 4th Ed; Washington D.C.,2000.

Paulden M, Palmer S, Hewitt C, Gilbody S. Screening for postnatal depression in primary care: cost effectiveness analysis. BMJ. 2009 Dec 23;339:b5203.

Depression Guideline Panel. Clinical Practice Guideline Number 5: Depression in Primary Care Volume 1: Detection and Diagnosis. Rockville, Md: HHS; AHCR publication; 1993:93-0550.

Diagnostic and Statistical Manual of Mental Disorders. 4th Ed. Washington, DC: American Psychiatric Association; 1994.

Cheung AH, Zuckerbrot RA, Jensen PS, GLAD-PC Steering Group, et al. Guidelines for Adolescent Depression in Primary Care (GLAD-PC) II. Treatment and Ongoing Management, Pediatrics. 2007;120(5):1313-26.

Clark MS, Jansen KL, Cloy JA. Treatment of Childhood and Adolescent Depression. AFP. 2012;86(5):442-8.

Nelson JC, Delucchi KL, Schneider LS. Moderators of outcome in late-life depression, a patient-level meta-analysis. Am J Psychiatry. 2013;170(6):651-9.

Eaton WW, Anthony JC, Gallo J. Natural history of diagnostic interview schedule/DSM-IV major depression. The Baltimore Epidemiologic Catchment Area follow-up. Arch Gen Psychiat. 1997;54(11):993-9.

American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry. 2000;157(4):1-45.

Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR* D: implications for clinical practice. American journal of Psychiatry. 2006 Jan 1;163(1):28-40.

Gaynes BN, Davis L, Rush AJ, Trivedi M, Fava M, Wisniewski SR. The aims and design of the Sequenced Treatment Alternatives to Relieve Depression (STAR* D) study. Primary Psychiatry. 2005 Feb;12(2):36-41.

Paykel ES, Ramana R, Cooper Z, Hayhurst H, Kerr J, Barocka A. Residual symptoms after partial remission: an important outcome in depression. Psychological medicine. 1995 Nov;25(6):1171-80.

Ginsberg LD, Oubre AY, DaouD YA. L-methylfolate plus SSRI or SNRI from treatment initiation compared to SSRI or SNRI monotherapy in a major depressive episode. Innovations in clinical neuroscience. 2011 Jan 1;8(1):19.

Nelson JC, Mazure CM, Jatlow PI, Bowers Jr MB, Price LH. Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study. Biological psychiatry. 2004 Feb 1;55(3):296-300.

Fava M, McCall WV, Krystal A, Wessel T, Rubens R, Caron J, et al. Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder. Biological Psychiatry. 2006 Jun 1;59(11):1052-60.

Keller MB. The long-term treatment of depression. J Clin Psychiatry. 1999;60(17):41-5.

Di Palma C, Urani R, Giorgetti V, Dalla Verde G. Is methylfolate effective in relieving major depression in chronic alcoholics? A hypothesis of treatment. Current therapeutic research. 1994 May 1;55(5):559-68.

Passen M, Cucinotta D, Abate G, Senin U, Ventura A, Badiale MS, et al. Oral 5′-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Aging Clinical and Experimental Research. 1993 Feb 1;5(1):63-71.

Stahl SM. Novel therapeutics for depression: L-methylfolate as a trimonoamine modulator and antidepressant-augmenting agent. CNS Spectr 2007;12(10):739-44.

Wesson VA, Levirr AJ, Joffe RT. Change in folate status with antidepressant treatment. Psychiatry Resrearch. 1994; 53(3):313-22.

Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol. 2005;19(1):59-65.

Papakostas GI, Iosifescu DV, Renshaw PF, Lyoo IK, Lee HK, Alpert JE, et al. Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II). Psychiatry Research: Neuroimaging. 2005 Dec 30;140(3):301-7.

Serot JM, Christmann D, Dubost T, Bene MC, Faure GC. CSF-folate levels are decreased in late-onset AD patients. J Neural Transm. 2001;108(1):93-9.

Chanson A, Cardinault N, Rock E, Martin JF, Souteyrand P, D’Incan M, et al. Decreased plasma folate concentration in young and elderly healthy subjects after a short‐term supplementation with isotretinoin. J Eur Aca of Dermatol and Venereol. 2008 Jan;22(1):94-100.

Kelly CB, Mcdonnell AP, Johnston TG, Mulholland C, Cooper SJ, Mcmaster D, et al. The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol. 2004 Dec;18(4):567-71.

Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: A HuGE review. Am J Epidemiol. 2007;165(1):1-13.

Godfrey PS, Toone BK, Bottiglien T, Laundy M, Reynolds EH, Carney MW, Flynn TG, Chanarin I. Enhancement of recovery from psychiatric illness by methylfolate. The Lancet. 1990 Aug 18;336(8712):392-5.

L-Methylfolate. (Monograph) Alternative Medicine Review. 2006;11(4):330-7.

OECD. OECD Guidelines for Testing of Chemicals [internet]. France: OECD Publishing; 2006. Section 4, Health effects: Test No. 425: Acute oral toxicity: Up and down procedure.

Detke MJ, Johnson J, lucki I. Acute and chronic antidepressant drug treatment in the rat forced swimming test model of depression. Exp Clin Psychopharmacol. 1997;5(2):107-12.

Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology. 1985 Mar 1;85(3):367-70.

Farah A. The role of L-Methylfolate in depressive disorder. CNS Spectrums. 2009;14(1):suppl 2:1-8.

Brocardo PS, Budni J, Kaster MP, Santos ARS, Rodrigues ALS. Folic acid administration produces an antidepressant-like effect in mice: evidence for the involvement of the serotonergic and noradrenergic systems. Neuropharmacol. 2008;54:464-73.

Stahl SM. Novel therapies for depression: l-methylfolate as a trimonoamine modulator and antidepressant agent. CNS Spectr. 2007;12:739-44.

Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM. Folate, vitamin B12, homocysteine, and the MTHFR 677C→ T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Archives of general psychiatry. 2003 Jun 1;60(6):618-26.

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Published

2018-08-23

How to Cite

More, S. A., Mishra, P. S., Tiwari, A., & Vyas, S. (2018). Evaluation of antidepressant activity of l-methylfolate per se and its interaction with escitalopram in mice. International Journal of Basic & Clinical Pharmacology, 7(9), 1721–1727. https://doi.org/10.18203/2319-2003.ijbcp20183478

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Original Research Articles