By Laurie Barclay, M.D.
Antibiotics do not improve cognitive symptoms of post-treatment chronic Lyme disease (PTCLD), according to the results of two randomized trials published in the June 24, 2003 issue of Neurology. The editorialist suggests that they should not be used in this condition, which may be a variant of chronic fatigue syndrome.
"Although encephalopathic symptoms have been attributed to PTCLD, objective evidence of cognitive dysfunction has been inconclusive and comes from a few relatively small studies," write Richard F. Kaplan, Ph.D., from the University of Connecticut School of Medicine in Farmington, and colleagues. "Moreover, there is little evidence that additional antibiotic therapy will improve cognitive functioning in this population."
Of 129 patients with Lyme disease diagnosed at three study sites in the northeast U.S., 78 were seropositive for IgG antibodies against Borrelia burgdorferi, and 51 were seronegative. In each group, patients were randomized to receive intravenous ceftriaxone 2 g daily for 30 days followed by oral doxycycline 200 mg daily for 60 days, or matching intravenous and oral placebos.
At baseline, there were no significant differences between seropositive and seronegative groups. Both groups reported many symptoms on the cognitive functioning, pain, and role functioning scales of the Medical Outcomes Study (MOS), as well as depression and somatic complaints on the Beck Depression Inventory and Minnesota Multiphasic Personality Inventory. However, both groups had normal baseline neuropsychological test scores for memory, attention, and executive functioning.
Between baseline and 90 days, the combined groups showed significant decreases in MOS symptoms, higher objective test scores, and improved mood, but there were no significant differences between patients receiving antibiotics and those receiving placebo.
"Patients with post-treatment chronic Lyme disease who have symptoms but show no evidence of persisting Borrelia infection do not show objective evidence of cognitive impairment," the authors write. "Additional antibiotic therapy was not more beneficial than administering placebo…. We suspect that the improvement on tests involving sustained attention and speed of processing was a combination of practice effect, less pain, and improved mood."
The National Institutes of Health supported this study.
In a separate study, L. B. Krupp, M.D., and colleagues, from Stony Brook University Medical Center in New York, evaluated 55 patients with Lyme disease with severe fatigue persisting at least six months after antibiotic therapy. In this single-center, double-masked trial, patients were randomized to receive 28 days of intravenous ceftriaxone or placebo.
Compared with the placebo group, patients in the ceftriaxone group had improvement in disabling fatigue (rate ratio, 3.5; 95% confidence interval, 1.50 – 8.03; P = .001). However, antibiotic treatment was not associated with improvements in cognitive function, defined by a change of at least 25% on a test of reaction time, or in the laboratory measure (outer surface protein A) of persistent infection. Of four patients who had adverse treatment events requiring hospitalization, three were receiving placebo.
The authors note that masking may have been compromised, because more patients in the ceftriaxone group than in the placebo-treated group correctly guessed their treatment assignment.
"Because fatigue (a nonspecific symptom) was the only outcome that improved and because treatment was associated with adverse events, this study does not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued patients with [PTCLD]," the authors write. "Nonetheless, the improvement in fatigue could be considered an encouraging finding in that future studies exploring other less expensive and noninvasive methods for treating severe fatigue might be effective."
Roche Laboratories supplied the active medication and placebo.
In an accompanying editorial, Israel Steiner, from Hadassah University Hospital in Jerusalem, Israel, notes that patient groups studied were heterogeneous, which may have obscured positive therapeutic findings.
"What are the take-home messages?" he writes. "Although these studies do not provide credence to the possibility that [PTCLD] is due to an infective process, at present the interpretation of the data does not prove that the condition does not exist, that there is no ongoing infection, or that the treatment protocols are or are not the appropriate ones. Most importantly, without an objective surrogate (preferably biological) marker to enable recruitment of homogenous study groups, every attempt to address clinical questions in the realm of [PTCLD] is doomed, almost by definition, to leave these questions unsettled."
Study Reference: Neurology. 2003;60:1888-1889, 1916-1922, 1923-1930
Reviewed by Gary D. Vogin, M.D.