Enhancement of recovery from mental illness with l-methylfolate supplementation

Perspect Psychiatr Care. 2018 Apr;54(2):331-334. doi: 10.1111/ppc.12227. Epub 2017 Jun 8.


People suffering from depression, schizophrenia, and dementia often have measurably lower levels of serum folate compared to people not experiencing psychiatric disorders. Augmentation of SSRI and SNRI antidepressant medications with l-methylfolate has been demonstrated to increase their effectiveness and onset of action. Even the use of l-methylfolate as a stand-alone monotherapy has been observed to exert antidepressant properties. The role of folate in mental illness has been known for many decades, but the strategic use of l-methylfolate supplementation has not yet been accepted as a standard regimen. It is the proposal of this paper that advanced nurse practitioners should consider the use of l-methylfolate as an adjunct to antidepressant medications at the initiation of therapy as part of a standard regimen in their clinical practice.

Keywords: augmentation; folate; folic acid; l-methylfolate; methylfolate; supplements.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Dietary Supplements*
  • Drug Therapy, Combination*
  • Humans
  • Mental Disorders / drug therapy*
  • Tetrahydrofolates / therapeutic use*


  • Antidepressive Agents
  • Tetrahydrofolates
  • 5-methyltetrahydrofolate