The risk of pain and fatigue after three weeks of Lyme disease treatment

Researchers at John Hopkins describe the risk of pain and fatigue after three weeks of treatment with doxycycline for an erythema migrans rash. According to the article published in Archives of Clinical Neuropsychology, 23 of 107 patients (21%) had a high fatigue total score and 33 of 107 patients (31%) had a high pain score. Only 5 of 107 patients (5%) had a high depression total score.

by Daniel J. Cameron, MD MPH

The cut-offs for fatigue and pain were chosen to reflect clinically significant levels of that symptom based on the literature. A cut-off of 36 or greater was chosen for the Fatigue Severity Score (FSS) to indicate “high fatigue symptoms.” A score of greater than 3 was chosen for the McGill Pain Scale to indicate “high pain symptoms.” A total score of 13 or greater was chosen for the Beck Depression Inventory as indicating clinically significant symptoms of depression.

There were a substantial number of patients with a high level of symptoms immediately after completion of the three weeks of doxycycline. “Thus by the end of standard antibiotic treatment (Visit 2), those with high (clinically significant) symptoms of fatigue, pain, or depression continue to have impact on life functioning up to 6 months later,” according to Bechtold from the Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine.

The researchers identified 6 individuals that suffered from Post-Treatment Lyme Disease Syndrome (PTLDS). The authors used the IDSA case definition of PTLDS as follows:

“a documented episode of early or late LD with post-treatment resolution of objective signs of LD, but continuation or subsequent onset of symptoms of fatigue, widespread musculoskeletal pain, and/or complaints of cognitive difficulties. These subjective symptoms must be continuous or relapsing for at least 6 months following completion of treatment and must be severe enough to reduce the patient’s functional ability.”

The remaining patients with severe fatigue and pain did not meet the PTLDS criteria. It would appear that studies of PTLDS clearly underestimate the morbidity associated with Lyme disease.

More: International Lyme and Associated Diseases Society Treatment Guidelines, 2014.



  1. Bechtold KT, Rebman AW, Crowder LA, Johnson-Greene D, Aucott JN. Standardized Symptom Measurement of Individuals with Early Lyme Disease Over Time. Arch Clin Neuropsychol. 2017;32(2):129-141.

25 Replies to "The risk of pain and fatigue after three weeks of Lyme disease treatment"

  • Brianna
    11/18/2020 (2:26 pm)

    I had lymes disease as a toddler. I was never treated for it.
    I am now 21 years old. I experienced hair thinning/ loss, fever, neck pain on the left side, and extreme fatigue. I went to my doctor and she told me I had a new infection of Lymes Disease. I took Doxy twice a day for 3 weeks straight. It is now 2 months post-treatment, I am back to feeling extremely fatigued, my hair is still falling out, and the pain on the left side of my neck still persists. Do you advise further treatment?

    • Dr. Daniel Cameron
      11/19/2020 (7:31 am)

      I have patients who benefit from treatment. Some doctors disagree. Only one of three NIH sponsored Lyme disease trials showed benefits of retreatment. I have seen patients with a new infection who also had an unresolved previous infection.

  • Nealey
    10/14/2020 (2:40 pm)

    My mate recently finished a 21 day treatment of doxycycline for a lyme disease diagnosis. This morning was his last dose. He developed the EM rash 6, possibly 8 weeks before going to the doctor. He has pain in his back that seems to move around a bit. It’s intermittent and he can’t actually desribe what it feels like. He has terrible anxiety, so much that he went to the er this weekend because he was convinced there was a tumor growing in his body. A ct scan didn’t present anything of the like. He remains in a constant state of Malaise.

    • Dr. Daniel Cameron
      10/14/2020 (2:50 pm)

      I look for other causes during and after treatment. I also typically use other antibiotic treatment regimen if the symptoms remain.

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