Disulfiram for Lyme Disease: Evidence, Benefits, and Risks

Disulfiram for Lyme disease has drawn attention as a possible treatment for persistent infection. Originally marketed in the United States as Antabuse for alcohol dependence, disulfiram causes unpleasant physical reactions with alcohol consumption, including headache, nausea, and hypotension. More recently, several studies have examined whether it may also have activity against Borrelia burgdorferi, the bacterium responsible for Lyme disease.

Borrelia burgdorferi has survival strategies that may allow it to persist in humans. “Current antibiotic therapies (e.g., doxycycline) for early Lyme disease have been shown to be less effective against stationary phase spirochetes,” wrote the authors.¹

Laboratory Evidence for Disulfiram

In 2006, disulfiram was identified as a potent inhibitor of stationary-phase B. burgdorferi persisters.¹

In vivo studies using a Lyme disease mouse model demonstrated that intraperitoneal disulfiram reduced cytokine levels, antibody titers, and overall B. burgdorferi burden in the heart, ear, and bladder in the 21-day post-treatment group.¹

In 2020, another research group examined minimum inhibitory concentration (MIC) testing to assess bacterial viability.

Investigators found that Borrelia bacteria were more likely to survive treatment with doxycycline and amoxicillin, but not cefuroxime, when compared with disulfiram.²

In a similar study, combinations of doxycycline, amoxicillin, and cefuroxime only mildly reduced the survival of Borrelia bacteria.

Clinical Experience With Disulfiram for Lyme Disease

In 2019, Dr. Kenneth Liegner described the use of disulfiram (DSF) in three patients with chronic relapsing borreliosis.³

“In two of the patients, DSF eliminated the need for retreatment with antibiotics during the observation period. The third patient was symptom-free for six months and retreated with DSF,” Liegner reported.³

In a later report, Liegner and colleagues found that 12 of 33 patients (36.4%) who completed one or two courses of high-dose therapy experienced an enduring remission, defined as remaining clinically well for at least six months without further anti-infective treatment.²

Side Effects of Disulfiram Treatment

Disulfiram can lead to significant adverse effects.

In Liegner’s first report, each of the three patients experienced adverse reactions ranging from fatigue to psychotic episodes.³

In a later analysis, investigators divided patients into high-dose (≥4 mg/kg/day) and low-dose (<4 mg/kg/day) groups.

The most common adverse reactions in the high-dose group included:

• Fatigue (66.7%)
• Psychiatric symptoms (48.5%)
• Peripheral neuropathy (27.3%)
• Mild to moderate elevation of liver enzymes (15.2%)

“Although patients on high dose disulfiram experienced a higher risk for adverse reactions than those on a low dose, high-dose patients were significantly more likely to achieve enduring remission,” wrote Liegner and colleagues.²

Survey Findings in PTLDS

The French Federation against Tick-Borne Diseases conducted a self-reported survey among individuals with post-treatment Lyme disease syndrome (PTLDS).

Pain and fatigue improvement were reported by 44% of the 16 patients who responded.¹

The authors also observed a higher sensitivity to disulfiram-related toxic effects in PTLDS patients (13 of 16 individuals) than in patients receiving disulfiram for alcohol dependence treatment (1 in 15,000).¹

Clinical Trial of Disulfiram for PTLDS

In 2019, a clinical trial investigating disulfiram for PTLDS was registered in the United States.

The planned 14-week randomized, double-blind, placebo-controlled pilot study was designed to evaluate the side effects, tolerability, and clinical effectiveness of disulfiram in 24 PTLDS patients between 18 and 65 years of age.¹

Participants were to receive either four or eight weeks of disulfiram therapy, titrated from 250 mg to 500 mg after the first week according to tolerance.

This trial has not been completed.

Clinical Perspective

Disulfiram is one of several repurposed drugs being investigated for Lyme disease. Laboratory and early clinical reports suggest potential activity, but the evidence remains limited and side effects can be substantial.

Further controlled studies are needed to determine the safety, optimal dosing, and true clinical effectiveness of disulfiram for Lyme disease and PTLDS.

Editor’s note: I was pleased to see that Custodio and colleagues included Lyme disease in their mini-review article “A Repurposed Drug in Preclinical and Clinical Development for the Treatment of Infectious Diseases.” I advise my patients to receive appropriate antibiotic treatment for Lyme disease before considering disulfiram.