The following article is a part of conference coverage from the American Psychiatric Nurses Association (APNA) 34th Annual Conference, held online from September 30 to October 4, 2020. The team at the Clinical Advisor will be reporting on the latest news and research conducted by leading nurses in psychiatry. Check back for more from APNA 2020.


Patients with treatment-resistant depression (TRD) who took supplements of L-methylfolate reported improved outcomes in depressive symptoms, reducing associated societal burden and healthcare costs, according to a poster presented at the American Psychiatric Nurses Association 2020 Annual Conference, held online from September 30 to October 4, 2020.1

There is a well-known link between folate deficiency and treatment-resistant depression, and patients with folate deficiency tend to respond poorly to antidepressants.2 Performing genetic testing of patients with TRD can help identify polymorphism in the gene for methylenetetrahydrofolate reductase (MTHFR).

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The use of L-methylfolate in individuals with MTHFR polymorphism as adjunct therapy to antidepressants improves major depressive disorder symptoms up to 2 times the rate of antidepressants alone, reported Carrie Goodwin, DNP, PMHNP-BC, and Virginia Conley, ARNP, PHMHNP-BC, of the University of Iowa College of Nursing.

The researchers sought to create treatment guidelines for the use of pharmacogenomic-guided antidepressant supplementation with L-methylfolate for TRD as well as to develop an algorithm that can be used to guide treatment decisions. A literature review was conducted to determine a consensus definition for treatment-resistant depression, the role of MTHFR and catechol-O-methyltransferase (COMT) genes in depression, and treatment considerations for L-methylfolate.

The authors found that supplementation with L-methylfolate bypasses the MTHFR gene polymorphism and restores neurotransmitter synthesis. In patients with the COMT gene val158met polymorphism, there is a 25% to 33% decrease in enzymatic function per allele. It was also found that people who receive L-methylfolate supplementation who have the COMT val158met allele will continue to experience “decreased catabolism of neurotransmitters” following supplementation; this may in turn lead to negative outcomes and adverse effects in certain populations.

Ultimately, the researchers determined that treatment decisions based only on MTHFR allele status are “too simplistic.” COMT val158met should also be evaluated and considered when making treatment decisions.

The treatment algorithm, developed for patients who are treated with more than 3 antidepressants or 1 antipsychotic in 1 year, demonstrated gaps in research and is currently pending submission for external evaluation and review.

“The guideline has the potential to reduce the prevalence of [treatment-resistant depression] as clinicians better understand how to interpret pharmacogenomics results and provide appropriate L-methylfolate supplementation,” the researchers concluded.

Visit Clinical Advisor’s meetings section for complete coverage of APNA 2020.


1. Goodwin C, Conley V. Genomic guided use of L-methylfolate in treatment resistant depression. Presented at: APNA 34th Annual Conference; September 30-October 4, 2020. Poster 74.

2. Shelton RC, Manning JS, Barrentine LW, Tipa EV. Assessing effects of L-Methylfolate in depression management: results of a real-world patient experience trial. Prim Care Companion CNS Disord. 2012;15(4):PCC.13m01520.