Letters Section Editor: Robert M. Golub,
MD, Senior Editor.
To the Editor: While the study by Dr Blacker
and colleagues1 demonstrates that galantamine
is not an effective treatment for persons with chronic fatigue syndrome (CFS),
I do not believe that this negative outcome represents an appropriate test
of the cholinergic hypothesis in the pathogenesis of CFS.
Soreq and Seidman2 and Brenner et al3 have demonstrated in animal models of posttraumatic
stress disorder and in Gulf War syndrome (a possible syndromic relative of
CFS) that cholinergic neurons produce sustained and excessive amounts of AChE-R,
an altered soluble variant of acetylcholinesterase. There is evidence that
the sustained production of AChE-R derails the cholinergic neurons from performing
their normal “signal-to-noise ratio” determination role in healthy
brain function.4 If there is a cholinergic
contribution to the pathogenesis of CFS, it would likely be the dysregulated
production of AChE-R. The failure of galantamine to favorably influence the
outcome of this syndrome could then be predicted because, being a cholinesterase
inhibitor, it is likely inducing overproduction of AChE-R.
Madill PV. Chronic Fatigue Syndrome and the Cholinergic Hypothesis. JAMA. 2004;292(22):2723. doi:10.1001/jama.292.22.2723-a