Contact: Elizabeth Streich
placebo-controlled study of cognitive impairment due to chronic Lyme disease
Findings show severe physical
dysfunction among patients & benefit of repeated IV antibiotic therapy to
provide long-term symptom relief
NEW YORK – Findings from the first
placebo-controlled study of chronic cognitive impairment after treated Lyme
disease (also known as chronic Lyme encephalopathy) demonstrate that patients
report moderate cognitive impairment, physical dysfunction comparable to
patients with congestive heart failure, and fatigue comparable to patients with
multiple sclerosis. In the study, repeated intravenous (IV) antibiotic therapy
was shown to be effective in treating cognitive dysfunction and the debilitating
pain, fatigue and physical dysfunction associated with this disease.
The study, titled “A Randomized,
Placebo-Controlled Trial of Repeated IV Antibiotic Therapy for Lyme
Encephalopathy,” will be published on-line by the journal Neurology on Oct. 10,
2007. The study was led by Principal Investigator Brian Fallon, M.D., M.P.H.,
director of the recently established Lyme and Tick-borne Disease Research Center
at Columbia University Medical Center (http://www.cumc.columbia.edu/news/press_releases/fallon_lyme_center.html).
The research was conducted jointly at the Columbia University Medical Center and
New York State Psychiatric Institute and was funded by the National Institute of
Neurological Disorders and Stroke (NINDS).
“These findings replicate results from a prior
placebo-controlled trial of post-Lyme fatigue, which found positive treatment
results from repeated antibiotic therapy. They also replicate the degree of
physical impairment results demonstrated in another prior study of chronic Lyme
disease,” said Dr. Fallon (*see citations below). “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.”
Dr. Fallon and his research team identified
patients with cognitive problems that developed after being diagnosed with Lyme
disease and which persisted or relapsed despite prior treatment, in order to
determine whether patients who have already received the “standard” course of
antibiotic treatment (three weeks of IV antibiotic therapy), would benefit from
an additional 10 weeks of antibiotic therapy. They also set out to determine
whether patients relapse when taken off antibiotics or whether the alleviation
of symptoms is sustained or enhanced with time.
Study participants (57 subjects: 37 patients
with a history of Lyme disease and 20 controls) were divided into three subject
groups: patients with a history of treated Lyme disease who were randomized to
IV treatment with an antibiotic called ceftriaxone for 10 weeks; patients with a
history of treated Lyme disease who were randomized to IV placebo for 10 weeks;
and, healthy controls who were tested at the same time points as the patients to
help to control for the practice effect on neuropsychological testing. All
patients had to meet criteria for memory impairment at the start of the study
and they were also required to have a positive IgG Western blot for Lyme disease
at study entry.
Key findings from the Neurology paper are as
- There was significantly greater improvement
in cognition in the antibiotic treated sample at the primary end point for
efficacy (week 12).
- When patients were retested three months
after antibiotic treatment, the initial gains in cognition for the
ceftriaxone-randomized sample were no longer present.
- Patients lose their cognitive improvement
when IV antibiotic therapy is stopped.
Pain, Fatigue and Physical Dysfunction
- Among patients with greater severity at the
start of the study, those randomized to ceftriaxone had more significant
symptom relief of pain, fatigue, and physical dysfunction at week 12, as
compared to those patients who did not receive ceftriaxone.
- Patients initially randomized to IV
ceftriaxone who had greater severity of symptoms at baseline continued to show
reduced pain and improved physical functioning at week 24. Improvement in
fatigue continued, but was no longer statistically different from placebo at
- Repeated IV antibiotic therapy is effective
in improving cognition, and among the more impaired, in improving pain,
fatigue, and physical dysfunction.
- 18.9 percent of the 37 patients had serious
adverse effects associated with either the IV line or a reaction to the
antibiotic itself. Although all fully recovered, IV antibiotic therapy has the
potential for serious risks, such as systemic infection, thrombus formation,
or allergic reactions.
- Repeated IV antibiotic therapy should be
considered a valuable option with long-term benefit for managing the disabling
symptoms associated with chronic Lyme disease.
- Given the risks and benefits associated with
IV antibiotic therapy, physicians and patients need to have a thoughtful
discussion prior to initiating treatment.
*Citations from Recently Published Research
- The percentage of patients with meaningful
improvement in fatigue noted at six months in this Neurology study (66.7
percent for patients treated with ceftriaxone vs. 25 percent for placebo) was
comparable to the improvement in fatigue noted after repeated IV ceftriaxone
therapy in a prior placebo controlled study (64 percent for drug vs. 18.5
percent for placebo) (Krupp et al., Neurology, 2003).
- The degree of physical impairment (comparable
to congestive heart failure) was comparable to the impairment noted in another
chronic Lyme study (Klempner et al., NEJM, 2001).
“Future research needs to focus on identifying a
treatment approach that either allows not only for acute efficacy, but also
long-term cognitive improvement; or, a treatment that could be given after the
IV antibiotic therapy that would allow for sustained or enhanced cognitive
improvement over time. Our Lyme and Tick-borne Disease Research Center continues
to work towards finding these solutions,” said Dr. Fallon. “The most important
lesson of this study is that physicians and patients need to collaborate openly
to design an individual treatment plan to manage the long-term and complex
suffering from symptoms of chronic Lyme disease.”
Columbia University Medical Center provides
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