Fever, headache, fatigue, and a characteristic “bull’s eye” rash are among the early symptoms of Lyme disease. Yet, while a single round of antibiotics will cure the majority of patients, doctors remain confused about how to treat people whose symptoms persist, affecting the joints, heart, and nervous system. For patients who can’t seem to shake this infection, a new European study shows that long-term treatment with antibiotics does not lead to better results than short-term treatment.

The Centers for Disease Control and Prevention report a total of 25,359 confirmed cases of Lyme disease in 2014, the most recent statistical year. In North America, Lyme disease is primarily caused by the bacteria Borrelia burgdorferi, which is transmitted by two species of blacklegged ticks. The European strain of B. burgdorferi is slightly different from what circulates on this side of the Atlantic, and infections manifest in different ways, Drs. Michael T. Melia and Paul G. Auwaerter wrote in an editorial accompanying the study. In fact, more than 300 separate strains of the Lyme disease bacteria exist worldwide, 100 in the United States alone, and many have developed some resistance to antibiotics.

Though the majority of Lyme disease patients improve after a round of antibiotics, about “10 to 20 percent of treated patients may have lingering symptoms of fatigue, musculoskeletal pains, disrupted sleep, and lack of customary mental functions,” Melia and Auwaerter wrote. Some of these patients may appear healthy for long periods, and their blood work may even look normal. (For this reason, doctors sometimes refer to it as the “invisible illness.”)

In the 40 years since the discovery of the disease, doctors have attempted to cure patients complaining of persistent Lyme disease symptoms by placing them on long-term antibiotics. However, no previous study has shown prolonged antibiotic treatment actually cures these patients. So, a research team, led by Dr. Bart Jan Kullberg, a professor of medicine and infectious diseases, conducted a double-blind investigation to compare three separate treatments.

Closing One Door

The Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) trial included 280 patients, all previously diagnosed with Lyme disease yet suffering ongoing symptoms, including muscle and joint pains, concentration problems, and fatigue. During the first two weeks, all participants were given the antibiotic ceftriaxon. Next, Kullberg and his colleagues divided these patients into three treatment groups and assigned the first group the antibiotic doxycycline, the second group a combination of the antibiotics clarithromycin and hydroxychloroquine, and the third group a placebo. A “double-blind” study, neither participants nor the doctors themselves knew which patient received which treatment throughout the 12-week period.

Both before and after treatment began, all the participants completed questionnaires recording their symptoms, fitness levels, quality of life, and wellbeing. The researchers also used memory tests and a pedometer for more objective measurements of each patient’s progress. Participants repeated these tests and survey questions after 26, 40, and 52 weeks.

At none of these time points did the researchers find clear differences between the groups. Based on the results, the researchers say long-term use of antibiotics does not help people diagnosed with Lyme disease who continue to report unexplained, persistent symptoms. Though, unfortunately, this leaves patients and their doctors in the dark, future research efforts can focus on new strategies that may potentially lead to a real cure.

Source: Berende A, ter Hofstede HJM, Vos FJ, et al. Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease. New England Journal of Medicine. 2016.