The Role of Ketamine Infusion for Patients with MS-Related Fatigue

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Low dose ketamine infusion may be a safe and tolerable treatment strategy for multiple sclerosis-related fatigue.

Low dose ketamine infusion may be a safe and tolerable treatment strategy for multiple sclerosis (MS)-related fatigue, according to study results published in Multiple Sclerosis Journal.

Chronic fatigue is a very common and disabling symptom of MS, but the pathophysiological mechanisms are poorly understood and there are no effective medications approved by the U.S. Food and Drug Administration for the treatment of MS-related fatigue. The objective of the current study was to assess the safety, tolerability, and efficacy of low-dose ketamine infusion for the treatment of MS-related fatigue.

This double-blind, randomized, active-placebo-controlled study included 18 patients with MS, recruited between February and August 2019 through advertisements and physician referrals from the Johns Hopkins Multiple Sclerosis Center. Participants were between 18 and 65 years old and were randomized to a ketamine (12 patients) or midazolam (6 patients) infusion. The primary study outcome was change in Daily Fatigue Severity for 7 days following a single intravenous infusion of low-dose ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). 

There was no change in Daily Fatigue Severity score during the first 7 days following infusion (-0.10 points; 95% CI, -0.32 to 0.12; P =.40). Additionally, there was no difference between the ketamine and midazolam groups regarding the trajectory of this score during the first 7 days following infusion (P =.40), indicating that low-dose ketamine infusion did not show statistically significant improvement in fatigue severity.

However, when MS-related fatigue was assessed using Fatigue Severity Scale, there was a trend in reduced Fatigue Severity Scale score at 1 week (-5.2 points; 95% CI, -10.4 to 0.14; P =.06). Furthermore, there was a clinically and statistically significant reduction in Modified Fatigue Impact Scale score at day 28 (-13.5 points; 95% CI, -25.0 to -1.98; P =.04).

The study had several limitations, including the pilot nature, relatively small sample size, negative results on the primary outcome, and the use of the Daily Fatigue Score, which was not a validated tool for MS fatigue research, as the primary outcome.

The study researchers concluded that “although the primary outcome of this study was negative, because ketamine infusion was associated with large, clinically significant and long-lasting changes in well-validated and multidimensional fatigue measures, we think these results can be the basis for performing a larger study of ketamine or other glutamate modulating agents for MS-related fatigue.”


Fitzgerald KC, Morris B, Soroosh A, et al. Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis–related fatigue. Mult Scler. Published online July 7, 2020. doi:10.1177/1352458520936226