galantamine – American ME and CFS Society

Abstract:

OBJECTIVE: Mental fatigue, cognitive disorders, and sleep disturbances seen in chronic fatigue syndrome (CFS) may be attributed to cholinergic deficit. A functional deficiency of cholinergic neurotransmission may cause the hypothalamic-pituitary-adrenal axis hypoactivity seen in CFS. Therefore, we investigated the alterations in stress hormones such as cortisol and dehydroepiandrosterone sulfate (DHEAS) in CFS patients before and after 4-week administration of galantamine hydrobromide, a selective acetylcholinesterase inhibitor, and aimed to investigate whether there are any relationships between the probable hormonal changes and cholinergic treatment.

METHODS: Basal levels of cortisol and DHEAS were measured in 29 untreated CFS patients who were diagnosed according to Centers for Disease Control (CDC) criteria and in 20 healthy controls. In the patient group, four weeks after 8 mg/d galantamine hydrobromide treatment, cortisol and DHEAS levels were measured again. After the treatment 22 patients who stayed in study were divided into two subgroups as responders and nonresponders according to the reduction in their Newcastle Research Group ME/CFS Score Card (NRG) scores.

RESULTS: Important findings of this study are lower pre-and post-treatment cortisol levels and in all CFS patients compared to controls (F=4.129, p=0.049; F=4.803, p=0.035, respectively); higher basal DHEAS values and higher DHEAS/cortisol molar ratios which were normalized following four weeks’ treatment with 8 mg/d galantamine hydrobromide in the treatment-respondent group (F=5.382, p=0.029; F=5.722, p=0.025, respectively).

CONCLUSION: The findings of the decrease in basal DHEAS levels and DHEAS/cortisol molar ratios normalizing with galantamine treatment may give some support to the cholinergic deficit hypothesis in CFS.

Source: Turan T, Izgi HB, Ozsoy S, Tanrıverdi F, Basturk M, Asdemir A, Beşirli A, Esel E, Sofuoglu S. The effects of galantamine hydrobromide treatment on dehydroepiandrosterone sulfate and cortisol levels in patients with chronic fatigue syndrome. Psychiatry Investig. 2009 Sep;6(3):204-10. doi: 10.4306/pi.2009.6.3.204. Epub 2009 Jun 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796068/ (Full article)

Abstract:

CONTEXT: There is no established pharmacological treatment for the core symptoms of chronic fatigue syndrome (CFS). Galantamine hydrobromide, an acetyl cholesterone inhibitor, has pharmacological properties that might benefit patients with CFS.

OBJECTIVE: To compare the efficacy and tolerability of galantamine hydrobromide in patients with CFS.

DESIGN, SETTING, AND PATIENTS: Randomized, double-blind trial conducted June 1997 through July 1999 at 35 outpatient centers in the United Kingdom (n = 17), United States (n = 14), the Netherlands (n = 2), Sweden (n = 1), and Belgium (n = 1) involving 434 patients with a clinical diagnosis of CFS (modified US Centers for Disease Control and Prevention criteria).

INTERVENTIONS: 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 3 times per day); a total of 82 patients received matching placebo tablets 3 times per day.

MAIN OUTCOME MEASURES: The primary efficacy variable was the global change on the Clinician Global Impression Scale after 4, 8, 12, and 16 weeks of treatment. Secondary outcomes were changes in core symptoms of CFS on the Chalder Fatigue Rating Scale, the Fibromyalgia Impact Questionnaire, and the Pittsburgh Sleep Quality Index; changes in quality of life on the Nottingham Health Profile; and assessment of plasma-free cortisol levels and cognitive performance on a computer-based battery of tests.

RESULTS: After 16 weeks, there were no statistically significant differences between any of the galantamine or placebo groups in clinical condition on the Clinician Global Impression Scale, or for any of the secondary end points. Exploratory regression analysis failed to detect any consistent prognostic factor that might have influenced the primary or any secondary outcome measures.

CONCLUSION: This trial did not demonstrate any benefit of galantamine over placebo in the treatment of patients with CFS.

Comment in:

Pharmacotherapy of chronic fatigue syndrome: another gallant attempt. [JAMA. 2004]

Chronic fatigue syndrome and the cholinergic hypothesis. [JAMA. 2004]

Source: Blacker CV, Greenwood DT, Wesnes KA, Wilson R, Woodward C, Howe I, Ali T. Effect of galantamine hydrobromide in chronic fatigue syndrome: a randomized controlled trial. JAMA. 2004 Sep 8;292(10):1195-204. http://www.ncbi.nlm.nih.gov/pubmed/15353532