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Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the Chronic Fatigue Syndrome (CFS)

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Because of the striking similarity of the clinical manifestations
produced by use of the drug reserpine and seen in patients
with the chronic fatigue syndrome (CFS), we theorized that
CFS was a disorder of reduced central sympathetic drive.
Because of the pharmacology of control of this central
sympathetic system, we further postulated that CFS symptoms
would respond quickly to low dose treatment with a monamine
oxidase inhibitor. To test these hypotheses, we designed a
randomized, double blind placebo controlled study using
phenelzine. No patient in the trial had a diagnosis of
lifetime or current psychiatric disorder and none had
depressed mood in the range of clinically depressed patients
on a paper and pencil test of depression. Patients in the
placebo group received placebo for 6 weeks while those in the
drug treatment group were treated in three 2-week
segments-placebo, 15 mg phenelzine every other day, and then
15 mg daily. This treatment regimen produced a significant
pattern of improvement compared to worsening in 20 self
report vehicles of CFS symptoms, illness severity, mood or
functional status. Thus the data support our hypothesis of
reduced sympathetic drive, although an alternative hypothesis
of pain alleviation is also possible. The study design also
allowed us to evaluate patients for a placebo effect: no
evidence for this was found, suggesting that CFS is not an
illness due to patients' being overly suggestible.

Natelson BH, Cheu J, Pareja J, Ellis SP, Policastro T, Findley TW

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