Treating fatigue: a novel and promising path forward



Fatigue is a common, distressing symptom and condition often associated with other medical conditions. The relationship between fatigue and depression is poorly understood, but it is believed that both conditions share common mechanisms. Like depression, fatigue has complex, elusive, and multifaceted causes, making successul treatment difficult to achieve.


Given that N-methyl-D-aspartate (NMDA) receptor antagonists, such as a low-dose ketamine, have well-documented rapid antidepressant effects in individuals with major depressive disorders, IRP researchers led by Leorey Saligan, Ph.D., R.N., C.R.N.P., and Carlos Zarate, M.D., hypothesized that similar anti-fatigue effects might also be present. In a randomized controlled trial of ketamine infusion for bipolar disorders, ketamine significantly lowered fatigue scores compared to placebo, and the effect remained significant after controlling for changes in non-fatigue depressive symptoms.


This study is the first to suggest that NMDA receptor inhibition is a potential therapeutic research target for fatigue, suggesting a novel potential role of the glutamatergic system. The results also validate the utility of the first clinician-administered fatigue questionnaire, the NIH-Brief Fatigue Inventory, to measure changes in fatigue symptoms in a clinical trial.


Saligan LN, Luckenbaugh DA, Slonena EE, Machado-Vieira R, Zarate CA Jr. (2016). An assessment of the anti-fatigue effects of ketamine from a double-blind, placebo-controlled, crossover study in bipolar disorder. J Affect Disord. 194:115-9.

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This page was last updated on Tuesday, June 13, 2023