The following article is part of conference coverage from the 2019 American Association of Nurse Practitioners Annual Meeting (AANP 2019) in Indianapolis, Indiana. Clinical Advisor’s staff will be reporting breaking news associated with research conducted by leading nurse practitioners. Check back for the latest news from AANP 2019.


Treatment-resistant major depressive disorder has a significant presence in the primary care patient population, and primary care providers — including nurse practitioners — should be aware of the pharmacologic and nonpharmacologic therapies available for these patients, according to research presented at the 2019 American Association of Nurse Practitioners annual meeting, held June 18 to 23 in Indianapolis, Indiana.

Amy Culbertson, APRN, DNP, FNP-BC, assistant professor at Georgetown University School of Nursing and Health Studies, outlined both the pharmacologic interventions, including ketamine, esketamine, and l-methylfolate, as well as the nonpharmacologic therapies such as omega-3 polyunsaturated fatty acids and magnesium for treatment-resistant major depressive disorder.

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Ketamine was originally used as an anesthetic but can also be used for pain and headaches, pediatric sedation, and depression. Ketamine is administered by intravenous infusion and acts on the N-methyl-D-aspartate receptors in the brain to improve neural functioning.

Esketamine is an enantiomer of ketamine and was approved for the treatment of depression in March 2019 by the Food and Drug Administration. Esketamine is administered as a nasal spray and, like ketamine, acts on the N-methyl-D-aspartate receptors in the brain.

L-methylfolate is an active metabolite of folate, or vitamin B9. L-methylfolate helps support neurotransmitters such as serotonin and is used to augment the effects of prescription antidepressants.

Transcranial magnetic stimulation is a nonpharmacologic therapy that uses magnetic fields for brain stimulation. The magnetic fields target regions of the brain that affect mood and can improve depression.

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Omega-3 polyunsaturated fatty acids are naturally found in foods such as fish, shellfish, nuts, and seeds. Polyunsaturated fatty acids are essential components of central nervous system functioning and may help reduce inflammation.

Magnesium is an element found in the human body that plays a role in cortisol regulation and enhances mechanisms of certain neurotransmitters.

Probiotics are bacterial supplements that aid in gut health. Probiotics act on the gut microbiome to restore health and improve production of neurotransmitters. Probiotics may also help to reduce inflammation.

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Culbertson A. An update on available therapies for treatment-resistant major depressive disorder. Presented at: American Association of Nurse Practitioners (AANP) Annual Meeting; June 18-23, 2019; Indianapolis, IN.