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Journal of Pharmacy Practice, Vol. 21, No. 4, 278-286 (2008)
DOI: 10.1177/0897190008318132

L-methylfolate in the Therapeutic Management of Major Depressive Disorder

Tracy S. Hunter, RPh, PhD

College of Pharmacy, Health Science Campus Tulsa, University of Oklahoma, Oklahoma, tracy-hunter{at}ouhsc.edu

Optimal levels of the bioactive folate are necessary for maintaining proper brain and body functioning. Folate deprivation and impaired folate metabolism are clinically associated with defects in the developing nervous system. Numerous studies implicate a deficiency of bioactive folate with an increased risk of major depressive disorder and other neuropsychiatric disorders. Bioactive forms of folate, particularly L-methylfolate, have been found to augment the therapeutic efficacy of antidepressants in patients with major depressive disorder, who fail to adequately respond to standard therapies. The antidepressant action of L-methylfolate appears to improve treatment outcomes most effectively when administered as an adjuvant to traditional antidepressants. This new understanding of the role of folates in major depressive disorder and other mood disorders offers opportunities to improve treatment outcomes.

Key Words: Folate therapy • major depression • L-methylfolate


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