Effect of Galantamine Hydrobromide in Chronic Fatigue Syndrome

Abstract

HRONIC FATIGUE SYNDROME (CFS) is a complex disorder characterized by long-term disability. The rate of spontaneous recovery in CFS is low 1 and no consistently effective treatment is available. Hypoactivity of the hypothalamicpituitary-adrenal axis has been demonstrated in some patients with CFS and fibromyalgia. 2-7 Some evidence suggests that CFS patients may have enhanced sensitivity of the peripheral cholinergic vascular system and an exaggerated pyridostigmine-stimulated growth hormone release response. 8 Acetylcholine is implicated in vagal tone, baroreceptor reflexes, and in transmission at the nicotinic sympathetic ganglia and at the neuromuscular junctions. Patients with CFS are often intolerant of the anticholinergic adverse effects of tricyclic antidepressants and these symptoms are similar to the symptoms of CFS. The frequent complaint of cognitive impairment in CFS also is consistent with the cholinergic hypothesis of cognition. A functional deficiency of cholinergic neurotransmission offers one possible explanation for the findings of a hypoactive hypothalamic-pituitary-adrenal axis; under conditions of stress, acetylcholine facilitates the release of corticotrophin-releasing hormone. Cholinergic stimulation also releases

The Placebo Response in the Treatment of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis

“…Out of 28 randomized controlled trials, 6 had a crossover design (49,70,73,75,96,97). In only two trials were the participants recruited from primary care (71,61). Six trials did not provide information on setting (49,68,73,80,83,96), but four of these recruited patients with poor baseline functioning or relatively severe illness (49,68,80,83), and one of them included only the patients with chronic mononucleosis syndrome (73).…”

“…Eight trials had interventions related to a low placebo effect (34 -36,72,77,93,100,103), 5 had medium effect interventions (38,61,70,75,83), and 16 had high effect interventions (28,49,56,62,64 -68,71,73,80,90,96,97,102). Five had used behavioral placebos such as relaxation or standardized medical care and hence were not double-blind (35,36,72,77,93), 16 had oral placebo (34,38,49,56,61,62,64,67,68,70,75,83,96,100,102,103), and 8 had injected placebo (28,65,66,71,73,80,90,97).…”

“…As the initial selection criteria, the outcome was computed only as binary. Twenty-two trials presented general outcomes (28,34,38,49,56,61,62,(65)(66)(67)(68)70,71,73,75,77,80,83,96,97,100,102) and seven trials physical outcomes (35,36,64,72,90,93,103). Study validity varied across the included trials.…”

The Case of Galantamine: Repurposing and Late Blooming of a Cholinergic Drug

“…In contrast, claims for chronic fatigue syndrome and fibromyalgia made in international patent application WO/1992/20327 were followed up by a Phase II clinical trial sponsored by Shire Pharmaceuticals, but failed to demonstrate efficacy [24]. …”

Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants

“…The acetyl cholesterone inhibitor galantamine was studied in CFS in a large, 16-week RCT (n = 434) [72]. Galantamine failed to separate from placebo on the primary efficacy measure of Clinician Global Impression or on any of the secondary outcome measures assessing the core symptoms of CFS, including the Chalder Fatigue Rating Scale, the Fibromyalgia Impact Questionnaire, the Pittsburgh Sleep Quality Index, and a computer-based cognitive performance battery.…”