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International Journal of Neuropsychopharmacology logoLink to International Journal of Neuropsychopharmacology
. 2025 Aug 18;28(Suppl 2):ii45. doi: 10.1093/ijnp/pyaf052.090

615. L-METHYLFOLATE: FROM NOVEL AGENT TO MAINSTREAM PSYCHIATRIC PRACTICE

V Mak 1,2
PMCID: PMC12359501

Abstract

Background

Folate augmentation of antidepressants has been a recognised treatment strategy in psychiatric practice for Difficult-To-Treat Depression, for well over a decade, yet few psychiatrists use this strategy, nor know the difference between the different forms of folate. L-Methylfolate is the biologically active form of folate and has been readily available in Australia and around the world for over 10 years.

Aims & Objectives

This presentation explores the factors which may affect the use of this strategy, the current evidence base, and future directions in research and clinical practice.

Method

Overview of folate metabolism. Case presentations.

Results

L-Methylfolate can be useful for patients with depression who have low or normal folate levels. There is no long-term safety data for high-dose L-Methylfolate. Low-dose L-Methylfolate appears effective, safe, well-tolerated and has high acceptance for targeted patients, as well as being low-cost and readily available. Currently, no clinical practice guidelines exist for the prescribing of L-Methylfolate.

Discussion & Conclusions

L-Methylfolate is under-utilised as an augmentation strategy for depression. It has the potential to substantially improve the clinical outcomes for many of our patients with Difficult-To-Treat Depression. Psychiatrists world-wide should consider this simple and effective strategy for their patients. The development of clinical practice guidelines would be helpful. Further research in L-Methylfolate augmentation and monotherapy will consolidate and expand the evidence base to inform clinical practice.


Articles from International Journal of Neuropsychopharmacology are provided here courtesy of Oxford University Press

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