NEW YORK, NY—The fourth randomized, placebo-controlled trial of repeated IV antibiotic therapy for cognitive impairment in patients previously treated for Lyme disease confirms earlier results showing no lasting improvement. Brian Fallon, MD, and colleagues report the study in Neurology.¹

"Like the other three, it clearly demonstrates the absence of any lasting improvement in cognitive function. Given the considerable risk of serious adverse events from prolonged antibiotic treatment, it is time to look elsewhere for an effective management strategy to help patients with persistent cognitive symptoms after treatment for Lyme disease," writes John J. Halperin, MD, in an accompanying editorial.²

RCT: 10 extra weeks of IV ceftriaxone or IV placebo

The study was designed to compare the effect of 10 weeks of IV ceftriaxone (Rocephin®) versus 10 weeks of IV placebo in patients with well-documented Lyme disease. These patients had received at least 3 weeks of prior IV antibiotics, had current positive IgG Western blots, and had memory impairment documented with the Wechsler Memory Scale. The primary outcome measure assessed neurocognitive performance of treated patients relative to placebo patients and to normal controls.

The study was meant to enroll 45 Lyme disease patients and to have randomized 30 to antibiotic and 15 to placebo, which would have provided an 80% power to detect an effect size of 1.1. Despite screening 3368 patients, the investigators were able to enroll only 37 Lyme disease subjects, 23 of whom had mild-to-moderate cognitive impairment as well as fatigue, pain, and impaired physical function, and were randomized to ceftriaxone. The remaining 14 subjects received placebo.

Patients were treated for 10 weeks and were assessed at week 12 with a battery of neurocognitive tests that included memory and a number of cognitive domains. The assessment was repeated at week 24 to determine durability of response. The primary outcome analysis showed that antibiotic treatment produced some improvement in cognitive function at week 12, but that improvement dissipated by week 24. Adverse effects attributable to IV ceftriaxone occurred in 26% of patients.

"Durability of benefit was assessed at week 24 after patients had been off of all treatment for 14 weeks. At this time point, there was no difference among the three groups in cognitive improvement from baseline," writes Dr. Fallon, at Columbia University in New York City. "Sustained improvement, however, was noted in physical functioning and current pain among patients with greater baseline impairment, suggesting that ceftriaxone may have both short- and long-term benefits for these symptoms."

Dr. Halperin is not impressed with this possibility, pointing out, "The authors then performed multiple post hoc analyses, an inherently problematic approach, in which innumerable questions can be framed until an interesting observation appears." He notes that the apparent improvement in pain in the most symptomatic patients does not take into account possible differences in concomitant pain management.

"Therefore, considering both the limited duration of cognitive improvement and the risks, 10 weeks of IV ceftriaxone and then 14 weeks of no antibiotic is not an effective strategy for sustained improvement," Dr. Fallon concludes.

References