Lack of efficacy of hydergine in patients with Alzheimer's disease. Double-blind clinical and psychologic study of ergoloid mesylates (Hydergine) in subjects with senile mental deterioration. [Dihydroergotoxine mesylate in the treatment of senile cerebral insufficiency. Result of a long-term multicenter double-blind clinical trial with a placebo]. Pharmacotherapy for organic brain syndrome in late life. Evaluation of an ergot derivative vs placebo. Ergoloid mesylates ('Hydergine') in the treatment of mental deterioration in the elderly: a 6-month double-blind, placebo-controlled trial. A clinical trial comparing 'Hydergine' with placebo in the treatment of cerebrovascular insufficiency in elderly patients. Influence of treatment on symptomatology and correlated electroencephalographic (EEG) changes in the aged. Combined hydrogenated alkaloids of ergot in mental and nervous disorders associated with old age.
There is no effective pharmacologic treatment for Alzheimer's disease, the most common dementing illness in the United States. Hydergine, a combination of ergoloid mesylates, is the only approved medication for Alzheimer's disease, but despite widespread use its efficacy remains to be established. We conducted a clinical trial of Hydergine-LC, a newer preparation of ergoloid mesylates in the form of a liquid in a capsule (LC) that may have greater bioavailability, to determine its value in patients with Alzheimer's disease.
                Eighty older adults with probable Alzheimer's disease participated in this double-blind, placebo-controlled trial of Hydergine-LC for 24 weeks. The recommended dose of 1 mg orally three times daily was used. Cognition and behavior were evaluated before and after the trial, and the patients were monitored for adverse effects. The medication was safe and well tolerated. The Hydergine-LC group did not perform better after treatment than the placebo group on any test, and its performance was worse (P less than 0.01 and P less than 0.02, respectively) on one cognitive measure (Wechsler Adult Intelligence Scale Digit Symbol Substitution Task) and on one behavioral scale (the Geriatric Evaluation by Relatives Rating Instrument).
                Hydergine-LC appears to be ineffective as a treatment for Alzheimer's disease. A double-blind study of 24 weeks' duration was conducted to investigate the effects of ergoloid mesylates (Hydergine) on symptoms of senile mental deterioration. Fifty-eight residents of old people's homes were included in the trial. Thirty were treated with ergoloid mesylates and 28 with placebo, and the effects of treatment were determined by means of medical and psychological examinations. On the Sandoz Clinical Assessment Geriatric Scale, the group receiving ergoloid mesylates showed significant improvement in all items. The group receiving placebo showed slight deterioration. Psychological examination showed that no changes were observed for either group in quantitative psychometric test results, although qualitative aspects of performance such as attention and concentration did improve. There was a close correlation between improved cognitive function scores on the SCAG and improved evaluations of behavior during the psychological examinations. There were marked individual differences in the degrees of improvement. Many controlled double-blind clinical trials against placebo and other drugs have clearly demonstrated the activity of dihydroergotoxine mesylate (DHT) on some symptoms of chronic senile cerebral insufficiency (CSCI). In spite of this, there is still some controversy about the usefulness of DHT for treatment of CSCI, as it seems to be hard to transpose the results of these studies to treatment of a population with DHT. Trying to overcome this criticism, a multicenter double-blind, placebo-controlled long-term (1 year) clinical trial has been planned, using very simple criteria for patient selection and easy to use assessment devices. Fifty two centres distributed throughout Italy were invited and 40 took active part in the study. The present report deals with data collected for analysis on Aug. 31, 1982. On this date 559 patients entered the study and 458 were under treatment (229 on DHT 1.5 mg t.i.d. and 229 on placebo). 101 patients dropped out (48 on DHT and 53 on placebo). 388 patients (195 on DHT and 193 on placebo) had completed 6 months and 204 (111 on DHT and 93 on placebo) had completed 1 year of treatment. The data from patients who completed 6 and 12 months of treatment period were analyzed statistically using Student t tests for paired and unpaired data, the large number of patients being adequate protection against any non normality in the distribution of the data. Differences with 2P values of 0.01 or less were considered significant.(ABSTRACT TRUNCATED AT 250 WORDS) Evaluation of treatment modalities, including pharmacotherapy, for organic brain syndrome (OBS) has been difficult because of sampling and methodological problems, and comparisons of research studies are all but impossible. In this study, an ergot derivative, a combination of dihydroergocornine mesylate, dihydroergocristine mesylate, and dihydroergokryptine mesylate (Hydergine) was compared with placebo, using a double-blind technique in a sample of nursing home residents with evidence of OBS. An 18-category symptom rating scale was used for periodic assessment over a six-month interval. Comparisons of the two groups of subjects disclosed that the Hydergine-treated group showed statistically significantly more improvement in most of the variables measured, especially during the last three months of treatment. Furthermore, sophisticated analysis revealed that positive changes in cognitive function cannot be accounted for as a mere reflection, or "halo" effect, associated with improved mood and general sense of well-being. A double-blind, placebo-controlled trial was carried out in 97 elderly patients with age-related mental deterioration to assess the efficacy of ergoloid mesylates in improving their symptoms. Patients were allocated at random to receive either 4.5 mg ergoloid mesylates per day or a matching placebo tablet and were followed-up for 6 months after the start of treatment. Clinical examinations were performed by the doctor, using the EACG rating scale (a French version of the Sandoz Clinical Assessment Geriatric scale), and by the nurse, using the NOSIE scale, when patients entered the trial and repeated after 2, 4 and 6 months. Changes in the factors (symptom groups) covered by these scales were subjected to statistical analysis. After 6-months' treatment, a statistically significant difference in favour of the ergoloid mesylates group was observed for cognitive deficits (p less than 0.05), anxiety and mood depression (p less than 0.01), unsociability (p less than 0.01), retardation (p less than 0.05) and irritability (p less than 0.001). Treatment was very well tolerated. It was also observed that there was a progressive increase in efficacy throughout the trial; this indicates that treatment with ergoloid mesylates in patients with mental deterioration should be long-term. nan nan nan
As in an earlier systematic review, we found hydergine to show significant treatment effects when assessed by either global ratings or comprehensive rating scales (based here on a smaller set of trials than in the earlier published systematic review because trials were required to have data that could conform with MetaView, the Cochrane Collaboration statistics software). The small number of trials available for analysis, however, limited the ability of subgroup analyses to identify statistically significant moderating effects.
Unfortunately, most of the randomized, double-blind, and placebo-controlled trials of hydergine were conducted and published before the advent of consensus-based diagnostic standards of dementia in 1984; therefore diagnostic criteria were less specific. As a result, uncertainty remains regarding hydergine's efficacy in dementia.