Executive Summary

SANDOZ' HYDERGINE, OTHER ERGOLOID MESYLATES BAN SOUGHT BY HRG on the grounds that the products are "ineffective" and "possibly harmful" to patients who may be suffering from Alzheimer's disease, Public Citizen's Health Research Group argued in a Feb. 12 petition to FDA. The petition asks that "ergoloid mesylates (Hydergine and others) be taken off the market and in the interim ... a 'Dear Doctor' letter be sent to all physicians notifying them of the ineffectiveness and possibly detrimental effects of ergoloid mesylates" in patients who may have Alzheimer's. HRG's request is based on the results of a study conducted by Troy Thompson, MD, et al., University of Colorado, published in the Aug. 16, 1990 New England Journal of Medicine. The double- blind, placebo-controlled study treated 80 adults with probable Alzheimer's disease with Hydergine-LC [liquid capsules] for 24 weeks. Patients received a dose of 1 mg orally three times daily. The advocacy group contends that the study shows Hydergine to be "totally ineffective, and to have possibly detrimental cognitive and behavioral effects, in patients with probable Alzheimer's." "The Hydergine-LC group did not perform better after treatment than the placebo group on any test, and its performance was worse . . . on one cognitive measure (Wechsler Adult Intelligence Scale Digit Symbol Substitution Task) and on one behavioral scale (the Geriatric Evaluation by Relatives Rating Instrument)," the study found. The investigators concluded that the drug "appears to be ineffective as a treatment for Alzheimer's disease." The HRG petition argues that the study "raises major doubts about the efficacy of [ergoloid mesylates] in other populations as well, because it is the first credible clinical trial of the drug." Ergoloid mesylates are manufactured by a number of other drug companies, including Rugby (Gerimal) and Ascher (Niloric). In response to the petition, Sandoz said that the research conducted by Thompson et al. is "one limited study of limited concern to us." The company noted that Hydergine has been marketed for over 30 years, and that there have been 50 positive studies of the drug. Sandoz added that while Thompson's study involved patients with mild dementia, Hydergine is indicated for treating moderate to severe cases of dementia. HRG acknowledged that "after three decades of study, there are more than 20 doubleblind, placebo-controlled trials of ergoloid mesylates which report statistically significant improvement among demented patients on various measures of outcome." However, the petition maintains that "there is considerable skepticism about this body of research." Sandoz first received approval for Hydergine sublingual tablets in 1953 for treatment of essential hypertension and peripheral vascular disease. Under FDA's DESI review, the drug was found to be possibly effective for neurological complaints in the elderly. Since the new beta blockers entering the market were more potent in treating hypertension, Sandoz dropped pursuit of Hydergine's use in hypertension. In 1973, Sandoz submitted five additional double-blind, controlled studies in support of the geriatric indication. In 1974, FDA found the sublingual tabs effective for treating symptoms of decline in mental capacity, such as depression and confusion, in the elderly. In 1981, FDA approved a labeling change that elaborated on the drug's use in treating dementia.