A pilot study of disulfiram for individuals with persistent symptoms despite prior antibiotic treatment for Lyme disease
Open accessAbstract
Introduction: . Case series suggest disulfiram may help to reduce the symptoms of patients with persistent symptoms despite prior antibiotic treatment for Lyme disease. This pilot study assessed safety, tolerability, and signs of clinical response. Materials and methods: Participants with a history of previously treated Lyme disease and persistent fatigue were randomly assigned in a double-blinded fashion to either Group A (disulfiram for 4 weeks and placebo for 4 weeks) or Group B (disulfiram for 8 weeks). Primary outcome endpoint was at 10 weeks with a follow-up at 14 weeks. The primary aim was to assess safety and tolerability. A clinical aim assessed signs of clinical improvement using well-validated measures, focusing on improvement in fatigue and quality of life. Target enrollment was 24 participants. Results: 940 individuals were screened, 11 were enrolled and nine participated in the trial. Dosing started low and increased based on response and tolerance to a maximum of 500 mg daily. Safety. Two participants discontinued medication due to clinical worsening, one of whom was briefly hospitalized. Three additional participants were withdrawn from treatment due to lab test abnormalities. Tolerability. Only three of nine participants completed the full course of treatment (two in Group A and one in Group B). Lower doses were better tolerated than the highest dose. Clinical response. Of nine participants, clinically meaningful improvement was noted in fatigue for six and in quality of life for four. Among the six fatigue responders, improvement was also noted on a multiple domain symptom index (six of six), overall symptom burden (five of six), and functional impairment (four of six). The study was terminated early due to end of project funding, higher than expected adverse events, and recognition that sufficient information was gathered to inform future studies. Conclusions and relevance: This study reveals the risks associated with disulfiram, especially at higher doses, while suggesting potential clinical benefits among some participants. Efficacy could not be assessed given the small sample size and the lack of a placebo-control group. Clinical trial registration: https://clinicaltrials.gov/study/NCT03891667?cond=Lyme%20Disease&intr=disulfiram&rank=1, NCT03891667.
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The pilot study evaluating disulfiram safety, tolerability, and clinical response in Lyme disease treatment (NCT03891667) highlighted risks, particularly at higher doses, where tolerability was poor.
“The pilot study evaluating DIS safety, tolerability, and clinical response in Lyme disease treatment (NCT03891667) highlighted risks, particularly at higher doses, where tolerability was poor.”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [30]
Although >50% of participants in the pilot study reported clinical benefit, the small sample size and lack of placebo control preclude definitive conclusions on disulfiram efficacy for persistent post-Lyme symptoms.
“Although >50% of participants reported clinical benefit, the small sample size and lack of placebo control preclude definitive conclusions on DIS efficacy for persistent post-Lyme symptoms.30”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [30]
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- Authors
- Kuvaldina, M., Preston, J., McClellan, D., Pavlicova, M., Brannagan, T. H., & Fallon, B. A.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Fallon, Brian A.
- Venue
- Frontiers in Medicine
- Publisher
- Frontiers Media SA
- Published
- 2025-04-02
- Volume
- 12
- Pages
- 1549324-1549324
- ISSN
- 2296-858X (ISSN-L)
- PMC
- PMC12013529
- OpenAlex
- W4409074378
- Cited by
- 2
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- FDC Foundation
- Topics
- Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Keywords
- disulfiram, post-treatment Lyme disease syndrome, persistent fatigue, quality of life, symptom burden, functional disability, drug safety and tolerability, dose escalation, adverse events
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