Effect of prolonged antibiotic treatment on cognition in patients with Lyme borreliosis

Neurology. 2019 Mar 26;92(13):e1447-e1455. doi: 10.1212/WNL.0000000000007186. Epub 2019 Feb 22.


Objective: To investigate whether longer-term antibiotic treatment improves cognitive performance in patients with persistent symptoms attributed to Lyme borreliosis.

Methods: Data were collected during the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) trial, a randomized, placebo-controlled study. Study participants passed performance-validity testing (measure for detecting suboptimal effort) and had persistent symptoms attributed to Lyme borreliosis. All patients received a 2-week open-label regimen of intravenous ceftriaxone before the 12-week blinded oral regimen (doxycycline, clarithromycin/hydroxychloroquine, or placebo). Cognitive performance was assessed at baseline and after 14, 26, and 40 weeks with neuropsychological tests covering the cognitive domains of episodic memory, attention/working memory, verbal fluency, speed of information processing, and executive function.

Results: Baseline characteristics of patients enrolled (n = 239) were comparable in all treatment groups. After 14 weeks, performance on none of the cognitive domains differed significantly between the treatment arms (p = 0.49-0.82). At follow-up, no additional treatment effect (p = 0.35-0.98) or difference between groups (p = 0.37-0.93) was found at any time point. Patients performed significantly better in several cognitive domains at weeks 14, 26, and 40 compared to baseline, but this was not specific to a treatment group.

Conclusions: A 2-week treatment with ceftriaxone followed by a 12-week regimen of doxycycline or clarithromycin/hydroxychloroquine did not lead to better cognitive performance compared to a 2-week regimen of ceftriaxone in patients with Lyme disease-attributed persistent symptoms.

Clinicaltrialsgov identifier: NCT01207739.

Classification of evidence: This study provides Class II evidence that longer-term antibiotics in patients with borreliosis-attributed persistent symptoms does not increase cognitive performance compared to shorter-term antibiotics.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Ceftriaxone / therapeutic use
  • Chronic Disease
  • Clarithromycin / therapeutic use
  • Cognition*
  • Double-Blind Method
  • Doxycycline / therapeutic use
  • Female
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Lyme Disease / drug therapy*
  • Lyme Disease / psychology
  • Male
  • Middle Aged
  • Neuropsychological Tests


  • Anti-Bacterial Agents
  • Hydroxychloroquine
  • Ceftriaxone
  • Clarithromycin
  • Doxycycline

Associated data

  • ClinicalTrials.gov/NCT01207739