Extra Antibiotics Provide Only Transient Improvement in Lyme Encephalopathy

NEW YORK, Oct. 11 -- If standard intravenous antibiotics don't relieve persistent or recurrent memory deficits in Lyme encephalopathy, an additional 10-day IV course of ceftriaxone (Rocephin) may do so -- but the benefit doesn't last.

Patients who received the extra 10 weeks of ceftriaxone had significantly better cognitive performance at week 12 than patients getting placebo infusions, reported Brian Fallon, M.D., M.P.H., of Columbia University here, and colleagues, online in Neurology.

But by 24 weeks the differences between groups in cognitive function had disappeared, the investigators found.

Although the cognitive benefit was transient, the additional course of ceftriaxone produced further improvements in physical functioning and decreases in pain and fatigue among patients with more severe disability at baseline, the authors wrote.

"The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24," the authors wrote. "On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning."

They said the results point out the need for physicians and patients to "collaborate openly to design an individual treatment plan to manage the long-term and complex suffering from symptoms of chronic Lyme disease."

The authors conducted a double-blind placebo-controlled study to determine whether the additional IV course of ceftriaxone had added benefit for patients who had shown only a partial or transient benefit from four weeks of IV therapy. They enrolled 37 patients with Lyme and 20 healthy volunteers, acting as controls, who had neuropsychological testing.

The patients had at least a three-week prior course of IV antibiotics, a current positive IgG Western blot, and object memory impairment, as determined by the Wechsler Memory Scale-III compared with age-, gender-, and education-adjusted population norms. The patients all had mild to moderate cognitive impairment, as well as significant levels of pain and fatigue and impaired physical functioning.

The Lyme patients were randomly assigned to 10 weeks of double-blind treatment with ceftriaxone or placebo, followed by 14 weeks of follow-up off all antibiotics.

The primary outcome was neurocognitive performance at week 12, as measured by tests for motor function, choice reaction, psychomotor function, attention, memory, working memory, and verbal fluency.

The authors saw that across the six cognitive domains, there was a significant treatment-by-time interaction favoring the antibiotic-treated group at week 12 (P=0.04).

There was a trend toward improvement of fatigue in this subgroup, but it was not significantly different from placebo at 24 weeks.

Adverse events from either the study medication or the peripherally inserted central catheter (PICC) occurred in 26.1% of patients (six of 23) on ceftriaxone compared with 7.1% of those on placebo; all patients recovered without additional injury, the authors noted.

"These findings replicate results from a prior placebo-controlled trial of post-Lyme fatigue, which found positive treatment results from repeated antibiotic therapy," Dr. Fallon said. "They also replicate the degree of physical impairment results demonstrated in another prior study of chronic Lyme disease. The door should be left open for physicians to prescribe medications as warranted, after a careful discussion with the patient of the potential risks and benefits."

The study was limited by its small sample size, inclusion criteria which restricted the sample to only 1% of screened patients, and by a lack of post-treatment lumbar puncture or neurologic exam, making it difficult to generalize the results to patients with Lyme disease but no cognitive impairment, or to patients with cognitive symptoms who are seronegative for B. burgdorferi infection, the authors acknowledged.