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

Abstract

ObjectiveTo investigate whether longer-term antibiotic treatment improves cognitive performance in patients with persistent symptoms attributed to Lyme borreliosis.MethodsData 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.ResultsBaseline 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.ConclusionsA 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.ClinicalTrials.gov identifierNCT01207739.Classification of evidenceThis 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.

Cognitive impairments in patients with persistent symptoms attributed to Lyme disease

“…The current study uses baseline data collected between 2010 and 2013 as part of the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE). Previously, we reported the primary and secondary outcome measures of this multicenter, placebo-controlled, double-blind randomized controlled trial from the Netherlands (ClinicalTrials.gov NCT01207739) [16, 17]. The local Institutional Review Board approved the PLEASE protocol, and informed consent was obtained from each participant.…”

Lyme borreliosis: diagnosis and management

“…While many patients report cognitive problems such as memory loss, word-finding difficulties, and lack of concentration, subjective memory complaints were not associated with impaired objective test performances in a prospective study on 279 patients with persistent symptoms attributed to Lyme borreliosis 153. Only 3% of patients included in that study were classified as having clinically impaired cognitive performance compared with normative data 154…”

“…While smaller studies reported limited, or non-sustained effects on selected outcomes,174175 the two largest trials did not find beneficial effects of prolonged treatment on any of the domains studied (table 2). 154173177182…”

Neuroborreliose

“…Zur Behandlung von Patienten mit nach einer behandelten Borreliose bestehenden persistierenden unspezifischen Beschwerden wie Fatigue oder kognitiven Einschränkungen liegen 4 randomisierte placebokontrollierte Studien vor, die keinen Anhalt für einen Nutzen einer zusätzlichen antibiotischer Therapie in diesen Fällen zeigen [4, 40 -42]. Des Weiteren zeigte eine aufwendige randomisierte placebokontrollierte Studie zur langfristigen antibiotischen Behandlung von Patienten mit unspezifischen Beschwerden und vermeintlicher Borreliose ohne vorangehende klare neurologische Symptome keinen Nutzen bezüglich der Lebensqualität sowie der Kognition [43,44].…”