Chronic fatigue syndrome (CFS) is a complex disorder characterized by long-term disability, according to background information in the article. There is no established pharmacological treatment for the core symptoms of CFS. Galantamine hydrobromide has pharmacological properties, including improving sleep quality, that researchers have speculated may benefit CFS patients. A pilot trial with CFS patients suggested that the drug might be helpful in CFS.

C.V. Russell Blacker, F.R.C.Psych., M.D., of the University of Exeter, England, and colleagues conducted a study to determine the efficacy and tolerability of galantamine hydrobromide in patients with CFS. The randomized, double-blind trial was conducted from June 1997 through July 1999 at 35 outpatient centers in Western Europe and the U.S. The study included 434 patients with a clinical diagnosis of CFS. A total of 89 patients were randomly assigned to receive 2.5 mg of galantamine hydrobromide; 86 patients, 5.0 mg; 91 patients, 7.5 mg; and 86 patients, 10 mg (these patients received medicine in the tablet form three times per day); a total of 82 patients received matching placebo tablets three times per day.

The researchers found that after 16 weeks there was no statistically significant differences between any of the galantamine or placebo groups in clinical condition, as measured by various tests and surveys.

"The lack of effect of galantamine on cognitive performance was surprising given the extent of the patients' cognitive impairment at baseline," the authors write. "In conclusion, in this study, galantamine did not provide a significant clinical benefit in the treatment of patients with CFS."

(JAMA. 2004; 292:1195-1204. Available post-embargo at JAMA.com)

Editor's note: This research was sponsored and funded by Shire Pharmaceutical Development Ltd.,
Andover, England. Dr. Blacker received research support from Shire Pharmaceutical Development Ltd.

Editorial: Pharmacotherapy of Chronic Fatigue Syndrome – Another Gallant Attempt

In an accompanying editorial, Stephen E. Straus, M.D., of the National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Md., examines the results of the trial conducted by Blacker et al.

"On its face, the study appears to be another in a virtually unbroken series of failed drug trials for CFS. Yet, by many criteria, the study is a resounding success. It pursued encouraging pilot data with a cholinesterase [an enzyme] inhibitor approved for the management of Alzheimer disease and its plausible underlying hypothesis that defects in [certain types of neurologic] pathways could also underlie some CFS symptoms. The present data further clarify, at least by exclusion, the pathogenesis of CFS."

"Fortunately for the science, but not for the patients, the results were unequivocal in that galantamine was well tolerated but yielded no meaningful benefits to any subset of patients. Yet the study reaffirmed the importance and feasibility of studying CFS rigorously, even if it remains a poorly understood and controversial illness," Dr. Straus concludes.