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December 8, 2004

Chronic Fatigue Syndrome and the Cholinergic Hypothesis—Reply

Author Affiliations

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2004;292(22):2723. doi:10.1001/jama.292.22.2723-b

In Reply: My colleagues and I were not proposing that our study was an exhaustive test of cholinergic mechanisms. However, anticholinesterases are now being used increasingly widely to treat other neurocognitive disorders such as traumatic brain injury and Parkinson disease. This, coupled with other observations in CFS, such as marked sensitivity to the anticholinergic adverse effects of tricyclic antidepressants, findings of cognitive impairment, and previous positive (and negative) trials involving both bethanechol and galantamine, led to a hypothesis that our many coinvestigators found persuasive. Our finding that these patients had measurable cognitive impairment that did not show a response to an anticholinesterase is an invitation for further research; we await a trial such as that recommended by Dr Madill.