Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis-related fatigue
Fatigue is the most common symptom of MS and has no effective pharmacotherapy. To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue. In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and rep...
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| Published in: | Multiple sclerosis Vol. 27; no. 6; p. 942 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
01.05.2021
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| Subjects: | |
| ISSN: | 1477-0970, 1477-0970 |
| Online Access: | Get more information |
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| Abstract | Fatigue is the most common symptom of MS and has no effective pharmacotherapy.
To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue.
In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models.
In total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (-0.10 point; 95% confidence interval (CI): -0.32, 0.12;
= 0.40). We observed a trend in reduced FSS scores at 1 week (-5.2 points; 95% CI: -10.4, 0.14;
= 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (-13.5 point; 95% CI: -25.0, -1.98;
= 0.04).
Ketamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS. |
|---|---|
| AbstractList | Fatigue is the most common symptom of MS and has no effective pharmacotherapy.
To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue.
In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models.
In total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (-0.10 point; 95% confidence interval (CI): -0.32, 0.12;
= 0.40). We observed a trend in reduced FSS scores at 1 week (-5.2 points; 95% CI: -10.4, 0.14;
= 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (-13.5 point; 95% CI: -25.0, -1.98;
= 0.04).
Ketamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS. Fatigue is the most common symptom of MS and has no effective pharmacotherapy.BACKGROUNDFatigue is the most common symptom of MS and has no effective pharmacotherapy.To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue.OBJECTIVETo determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue.In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models.METHODSIn this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models.In total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (-0.10 point; 95% confidence interval (CI): -0.32, 0.12; p = 0.40). We observed a trend in reduced FSS scores at 1 week (-5.2 points; 95% CI: -10.4, 0.14; p = 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (-13.5 point; 95% CI: -25.0, -1.98; p = 0.04).RESULTSIn total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (-0.10 point; 95% confidence interval (CI): -0.32, 0.12; p = 0.40). We observed a trend in reduced FSS scores at 1 week (-5.2 points; 95% CI: -10.4, 0.14; p = 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (-13.5 point; 95% CI: -25.0, -1.98; p = 0.04).Ketamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS.CONCLUSIONSKetamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS. |
| Author | Balshi, Alexandra Morris, Bridget Soroosh, Aurash Kaplin, Adam Maher, Dermot Fitzgerald, Kathryn C Nourbakhsh, Bardia |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32633662$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_msard_2025_106528 crossref_primary_10_1016_j_cct_2023_107106 crossref_primary_10_1016_j_jad_2024_08_183 crossref_primary_10_3390_ph18091298 crossref_primary_10_3390_ijms241612631 crossref_primary_10_1016_S2665_9913_23_00007_3 crossref_primary_10_1080_14737175_2022_2106854 crossref_primary_10_1177_02698811211021588 crossref_primary_10_1111_cns_70167 crossref_primary_10_1007_s40120_022_00363_7 crossref_primary_10_14336_AD_2024_0239 crossref_primary_10_1016_j_msard_2025_106352 crossref_primary_10_1016_j_neubiorev_2022_104762 |
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| Snippet | Fatigue is the most common symptom of MS and has no effective pharmacotherapy.
To determine the tolerability, safety, and efficacy of low-dose ketamine... Fatigue is the most common symptom of MS and has no effective pharmacotherapy.BACKGROUNDFatigue is the most common symptom of MS and has no effective... |
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| SubjectTerms | Double-Blind Method Fatigue - drug therapy Fatigue - etiology Humans Ketamine - adverse effects Multiple Sclerosis - complications Multiple Sclerosis - drug therapy Pilot Projects Treatment Outcome |
| Title | Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis-related fatigue |
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