title: Doxycycline-mediated effects on persistent symptoms and systemic cytokine responses post-neuroborreliosis: a randomized, prospective, cross-over study.
abstract: BACKGROUND
  Persistent symptoms after treatment of neuroborreliosis (NB) are well-documented, although the causative mechanisms are mainly unknown. The effect of repeated antibiotic treatment has not been studied in detail. The aim of this study was to determine whether: (1) persistent symptoms improve with doxycycline treatment; (2) doxycycline has an influence on systemic cytokine responses, and; (3) improvement of symptoms could be due to doxycycline-mediated immunomodulation.
  
  
  METHODS
  15 NB patients with persistent symptoms ≥6 months post-treatment were double-blindly randomized to receive 200 mg of doxycycline or a placebo for three weeks. After a six-week wash-out period, a cross-over with a three-week course of a placebo or doxycycline was conducted. The primary outcome measures were improvement of persistent symptoms assessed by neurological examinations, a symptom severity score and estimation of the quality of life. The secondary outcome measure was changes in systemic cytokine responses.
  
  
  RESULTS
  All 15 patients finished the study. No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events.
  
  
  CONCLUSIONS
  No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events. To conclude, in this pilot study, doxycycline-treatment did not lead to any improvement of either the persistent symptoms or quality of life in post-NB patients. Accordingly, doxycycline does not seem to be the optimal treatment of diverse persistent symptoms post-NB. However, the results need to be confirmed in larger studies.
  
  
  BACKGROUND
  NCT01205464 (clinicaltrials.gov).
authors.affiliation: Clinic of Infectious Diseases, University Hospital, SE-58185, Linköping, Sweden. johanna.sjowall@liu.se
authors.forename: Johanna
authors.initials: J
authors.lastname: Sjöwall
authors.forename: Anna
authors.initials: A
authors.lastname: Ledel
authors.forename: Jan
authors.initials: J
authors.lastname: Ernerudh
authors.forename: Christina
authors.initials: C
authors.lastname: Ekerfelt
authors.forename: Pia
authors.initials: P
authors.lastname: Forsberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism*; D004311:Double-Blind Method; D004318:Doxycycline / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D020852:Lyme Neuroborreliosis / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007155:Immunologic Factors; D010919:Placebos; D004318:Doxycycline