Perspective: Don’t trust single-dose doxycycline to prevent Lyme disease
Clinicians will often advise patients who have a tick bite to take a single dose of doxycycline to prevent Lyme disease. But this recommendation is based only on findings from one study, which showed that doxycycline prevented patients from developing an EM (or bull’s-eye) rash. It did not demonstrate that the antibiotic stopped patients from developing other manifestations of Lyme disease.
“A single 200 mg dose of doxycycline administered orally was reported to have been successfully used to prevent the development of erythema migrans at the bite site of Ixodes scapularis ticks,” writes Wormser in an article entitled “Doxycycline for Prevention of Spirochetal Infections-Status Report.” 
Wormser offers no evidence that a single 200 mg dose of doxycycline is effective at preventing other manifestations of Lyme disease, besides an erythema migrans rash.
Instead, he focuses on the prevention of a rash in a small study which he claims supports the prophylactic use of doxycycline to prevent Lyme disease. The study found 8 erythema migrans rashes at the site of a tick bite in individuals who were treated with a placebo. But only 1 erythema migrans rash at the site of a tick bite in individuals who were treated with a single 200 mg dose of doxycycline. A single dose of doxycycline may prevent a bull's-eye rash but not other manifestations of Lyme disease. Click To Tweet
However, the actual efficacy rate is uncertain in such a small sample. “The efficacy rate was 87%, but the 95% CI was wide-ranging from as high as 98% to as low as 25% based on the test-based method,” writes Wormser. 
The study did not look at whether a single 200 mg dose of doxycycline was effective at preventing manifestations of Lyme disease that can be devastating to patients, such as Lyme encephalopathy,  Neuropsychiatric Lyme disease,  Lyme arthritis,  and Post-Treatment Lyme disease syndrome. [6,7]
In the 2000 and 2006 Infectious Diseases Society of America (IDSA) treatment guidelines, Wormser and colleagues recommended a single 200 mg dose of doxycycline to prevent an erythema migrans rash at the site of a tick bite. 
The IDSA guidelines’ authors did not discuss whether a single 200 mg dose of doxycycline was effective at preventing other manifestations of Lyme disease.
Meanwhile, the 2014 International Lyme and Associated Diseases Society (ILADS) guidelines advised against a single 200 mg dose of doxycycline without evidence that this dosage would effectively prevent other manifestations of Lyme disease. 
The 2014 ILADS guidelines raised a concern that a single 200 mg dose of doxycycline might lead to a negative test. ILADS, instead, recommends a 3-week course of antibiotics or watchful waiting.
Wormser and colleagues did not address the concerns raised by the ILADS guidelines’ authors. Furthermore, Wormser was not certain that a single dose of doxycycline to prevent Lyme disease might also prevent the tick-borne infections Anaplasma phagocytophilum or Borrelia miyamotoi.
Wormer did not propose further studies to examine the effectiveness of a single dose of doxycycline. Instead, he suggested conducting a study that would include administering 200 mg doses of doxycycline on a weekly basis, from late June through July, the peak season for ticks in the Northeastern USA.
Editor’s note: For the purpose of full transparency, I’m an author of the 2014 ILADS guidelines. I remain opposed to the proposed weekly study until doctors can demonstrate that a single 200 mg dose can prevent other manifestations of Lyme disease, besides an EM rash.
- Wormser GP. Doxycycline for Prevention of Spirochetal Infections-Status Report. Clin Infect Dis. 2020.
- Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001;345(2):79-84.
- Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med. 1990;323(21):1438-1444.
- Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994;151(11):1571-1583.
- Steere AC, Malawista SE, Hardin JA, Ruddy S, Askenase W, Andiman WA. Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum. Ann Intern Med. 1977;86(6):685-698.
- Rebman AW, Bechtold KT, Yang T, et al. The Clinical, Symptom, and Quality-of-Life Characterization of a Well-Defined Group of Patients with Posttreatment Lyme Disease Syndrome. Front Med (Lausanne). 2017;4:224.
- Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134.
- Wormser GP, Nadelman RB, Dattwyler RJ, et al. Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Clin Infect Dis. 2000;31 Suppl 1:1-14.
- Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014;12(9):1103-1135.