Paper abstracts on hydergine

Hydergine In Brain Aging

Curr Med Res Opin 1989;11(6):380-9
Ergoloid mesylates ('Hydergine') in the treatment of mental deterioration in the elderly: a 6-month double-blind, placebo-controlled trial.

Rouy JM, Douillon AM, Compan B, Wolmark Y. Centre de Soins, C.H.U.R., Nime, France.

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.

J Am Geriatr Soc 1987 Mar;35(3):219-23
A controlled double-blind study of high-dose dihydroergotoxine mesylate (Hydergine) in mild dementia.

Thienhaus OJ, Wheeler BG, Simon S, Zemlan FP, Hartford JT.

In a double-blind study of 41 outpatients aged 55 to 80 years with mild memory impairment, the efficacy of dihydroergotoxine mesylate (DEM, Hydergine) at 6 mg per day, administered orally, was tested during a twelve-week period. Specific etiologies for the amnesic syndrome were ruled out by history, physical examination, and laboratory tests. Subjects with a Hamilton Depression Scale rating above 18, ie, possible pseudodementia, were excluded. Physician rating of memory, employing the Inventory of Psychic and Somatic Complaints in the Elderly (IPSC-E), indicated statistically significant improvement of memory function in DEM treated subjects (N = 22) v those on placebo (N = 19), (F = 3.34; df = 1,39; P less than .04). In contrast, structured testing of recent memory using digit symbol substitution and Zahlenverbindungs test (ZVT) showed improvement in both groups (P less than .001) with no significant intergroup differences (P less than .10). Our results indicate that in cases of mild, though subjectively distressing impairment, DEM at higher dosages may help to enhance short-term memory function.

Curr Med Res Opin 1986;10(4):256-79
Effects of long-term ergoloid mesylates ('Hydergine') administration in healthy pensioners: 5-year results.

Huber F, Koberle S, Prestele H, Spiegel R.

Five-year results are reported of a controlled long-term comparative study to assess the effects of ergoloid mesylates (1.5 mg 3-times daily) and placebo on medical, psychological and electrophysiological variables. Initially, 148 healthy elderly volunteers of both sexes were included. Eighty-nine subjects (48 on ergoloid mesylates and 41 on placebo) are still in the double-blind study; 39 subjects have left the trial for various reasons (6 deaths, 25 drop-outs due to disease, and 8 withdrawals) and 20 subjects are participating under 'open' conditions. Formal statistical comparison of the two groups in terms of 10 medical and psychometric outcome variables did not produce significant differences. However, a number of relevant findings and trends with regard to the effects of ergoloid mesylates were established: the drug was well tolerated objectively and subjectively; subjective complaints such as frequent dizziness, cardiac symptoms and leg cramps were improved; there was less increase than on placebo in the number of subjects with pathological ECG findings; there was less increase than on placebo in the number of subjects taking digitalis; fewer subjects than in the placebo group had an increase in the number of major diagnoses; the decrease in some lipid fractions was more pronounced than on placebo; and performance in some psychometric tests (WAIS Vocabulary, WAIS Performance) was better in the ergoloid mesylates group. None of these findings, by itself, would be evidence of a dramatic effect of ergoloid mesylates on the participants in the double-blind trial. Taken together, however, they fall into a pattern, suggesting that ergoloid mesylates was partly effective in maintaining physical and mental health in these healthy elderly individuals. The finding of more disease-related and symptom-related drop-outs in the placebo group (25 vs. 20 in the ergoloid mesylates group) supports this assumption. Furthermore, the fact that a number of subjects who had left the double-blind trial for medical reasons improved on subsequent ergoloid mesylates administration may be seen as a further argument in favour of a prophylactic effect of ergoloid mesylates on pathological concomitants of ageing.

Gerontology 1984;30 Suppl 1:3-52
A long-term study with co-dergocrine mesylate (Hydergine) in healthy pensioners. Results after 3 years.

Koberle S, Spiegel R.

Started in 1976, a long-term study in healthy pensioners is now in progress in Basel, Switzerland, to investigate medical, psychological, and electrophysiological aspects of the normal aging process and to establish whether these can be influenced by drug treatment. The subjects are receiving co-dergocrine mesylate (Hydergine) 1.5 three times daily or placebo orally under double-blind conditions. At 1-year intervals each subject's case history is reviewed, a clinical examination and laboratory tests are carried out, an ECG and an EEG are recorded, and a shortened form of the Hamburg-Wechsler Intelligence Test for Adults (German version of the WAIS, i.e., the Wechsler Adult Intelligence Scale), the Raven Coloured Progressive Matrices Test, and the Maudsley Personality Inventory are administered. Treatment compliance is being monitored by pill counting and determination of drug plasma levels. The results after 3 years of the study are presented. The subjects included in this evaluation are those who have undergone all examinations under double-blind conditions (n = 99). During the 3-year period, 27 of the 148 subjects (64 women and 84 men, mean age 63 years) initially recruited for the study have withdrawn, mainly because serious illness has supervened. Three subjects in the placebo group and 1 in the co-dergocrine mesylate group have died. The double-blind code has been broken for medical reasons in 18 cases; these subjects have continued to participate under open conditions. During this 3-year period, the following changes have been observed: A slight but statistically significant rise in systolic and diastolic blood pressure in the sample as a whole (mean increase 12 mm Hg). A decrease in systolic blood pressure in subjects with high initial values (mean decrease 6 mm Hg in the placebo group, and 18 mm Hg in the co-dergocrine mesylate group). An increase in systolic blood pressure in subjects with low initial values (mean increase 17 mm Hg in the placebo group and 16 mm Hg in the co-dergocrine mesylate group). A significant decrease in pulse rate in all subjects (mean decrease 7 beats/min). An increase in the number of subjects with pathological ECGs. A significant decrease in mean serum creatinine and lipid levels (all subjects) and a decrease of about 70% in the number of subjects with pathologically raised values. A decrease in the number of subjects from both groups with pathological signs in the EEG.

J Am Geriatr Soc 1983 Sep;31(9):549-55
A controlled long-term study with ergoloid mesylates (Hydergine) in healthy, elderly volunteers: results after three years.

Spiegel R, Huber F, Koberle S.

A long-term clinical comparison of the effects of ergoloid mesylates and placebo on 148 healthy elderly volunteers of both sexes was analyzed after three years of study. At that point, 99 subjects (53 receiving ergoloid mesylates and 46, placebo) were still being treated under double-blind conditions, while the remainder either had dropped out or continued to participate under open conditions. Many subjects in both groups were healthier after the three years than they had been at the onset of the study: subjective symptoms such as tiredness and dizziness were reduced, performances on tests of intelligence were improved, and some abnormal laboratory values had normalized. Blood pressures increased on the average during the investigational period and pulse rates became slower. The ergoloid mesylate regimen was well tolerated objectively and subjectively. Additional medical and psychologic improvements were noted in the group treated with ergoloid mesylates concerning cardiovascular parameters, cholesterol levels, subjective symptoms, and performances on tests of intelligence. These intermediate findings are interpreted as showing a preventive effect of ergoloid mesylates against some of the debilitating physical and psychologic concomitants of aging.

Pharmakopsychiatr Neuropsychopharmakol 1979 Nov;12(6):407-22
Hydergine: a review of 26 clinical studies.

McDonald RJ.

This report reviews 26 clinical drug trials which investigated the effectiveness of Hydergine, a dihydrogenated ergot alkaloid, used frequently in geriatric psychopharmacology. The methodological characteristics and significant results for each study are presented in outline form. In total, 32 symptoms were assessed in six or more studies. Therapeutic benefits following Hydergine treatment occurred in the areas of cognitive dysfunctions, mood depression, and the composite scores as measured by subjective clinical behavioral rating scales. It is suggested that the improvement reported in cognitive functions and mood depression is a reflection of the global change observed by clinicians in patients' overall behavior during the interview. This conclusion that Hydergine does produce some global improvement indicates that further research with Hydergine is warranted, provided more objective instruments are employed such as those described in the report.

J Clin Pharmacol. 1979 Nov-Dec;19(11-12):726-32.
The effects of an ergot alkaloid derivative (Hydergine) on aspects of psychomotor performance, arousal, and cognitive processing ability.

Hindmarch I, Parrott AC, Lanza M.

Hydergine, 12 mg per day for two weeks, has some direct activity on a variety of tasks of mental and cognitive performance. These results add support to biochemical findings that implicate the ergot alkaloids (particularly co-dergo-crine, Hydergine) in cellular activity likely to increase cortical arousal and awareness. The high dose of Hydergine used in this volunteer study was exceptionally well tolerated and did produce significant results on individual measures of central nervous system activity which might suggest the use of similar doses in patient populations. The findings of a hangover of activity after drug withdrawal and the fact that some CNS activity (serial subtraction of 17s) is not obvious until two weeks of medication would suggest the need for pharmacokinetic measures to be taken in conjunction with psychologic assessments. It would seem that a two-week schedule of repeated doses is the minimum required to produce an effect on CNS activity, but even with such a dose regimen it appears that the drug continues to exert some effect after its withdrawal.

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J Am Geriatr Soc 1979 May;27(5):198-202
Electroencephalographic and clinical changes as correlated in geriatric patients treated three months with an ergot alkaloid preparation.

Matejcek M, Knor K, Piguet PV, Weil C.

The results of a 3-month trial with an ergot alkaloid preparation (Hydergine) in 16 geriatric patients showed that, in accordance with a previously proposed working hypothesis, the improvement induced by the drug in electroencephalographic age-related changes was accompanied by clinical improvement in patients with similarly age-related mental deterioration.

J Am Geriatr Soc 1975 Apr;23(4):169-74
Mental decline in the elderly: pharmacotherapy (ergot alkaloids versus papaverine).

Rosen HJ.

This is the first double-blind study in outpatients to evaluate the effectiveness of dihydrogenated ergot alkaloids (DEA) (Hydergine) versus papaverine in the treatment of selected symptoms associated with mental aging. In addition, this is the first study comparing these two pharmacologic agents in relatively young geriatric patients, with a mean age in the mid-sixties. After twelve weeks of treatment, ratings of overall clinical condition and global change showed that the 26 patients given DEA improved more than twice as much as the 27 patients given papaverine. Of the 14 individual symptoms rated, 13 improved significantly more in the DEA group than in the papaverine group. These symptoms included confusion, dizziness, unsociability, depressive mood, and mental alertness. Other data confirmed the generally superior results with DEA. In view of its demonstrated beneficial clinical actions and of its notable scarcity of contraindications or side effects, DEA appears to represent a significant pharmacologic contribution to the care of elderly persons showing selected symptoms of mental and functional decline.

Hydergine In Dementia

Alzheimer's Research (United Kingdom) , 1996, 2/3 (79-84)
Efficacy of pyritinol versus hydergine upon cognitive performance in patients with senile dementia of the Alzheimer's type: A double-blind multi-center trial

In this multi-center trial, 100 patients with the diagnosis of Senile Dementia of the Alzheimer's type (SDAT) of mild to moderate severity were randomly divided into two treatment groups and, following a placebo wash-out phase, were administered either pyritinol or hydergine for 12 weeks in a double-blind, randomized parallel comparison. Two measures of cognitive functioning were employed to assess treatment effects. The results indicated that treatment with pyritinol was associated with a significant and continuous improvement in cognitive functioning over the course of the study while treatment with hydergine was associated with a more modest improvement that tended to plateau early in the treatment phase.

Age (USA) , 1995, 18/1 (5-9)
Hydergine revisited: A statistical analysis of studies showing efficacy in the treatment of cognitively impaired elderly

The pharmacologic treatment of dementia has received much attention in recent years. Hydergine, one of only two drugs approved by the Food and Drug Administration (FDA) for the treatment of dementia, was largely abandoned in the 1980's due to the uncertainty of its degree of clinical efficacy. The purpose of our study was to more precisely define the effect of Hydergine on cognitive function in elderly demented patients by combining the results of multiple weighted studies using similar methodology. All data came from randomized placebo controlled trials on a total of 271 subjects. Our results show that Hydergine had a statistically significant effect on global functional status compared to placebo, with the most significant improvement demonstrated on symptoms of depression, emotional lability, and indifference to surroundings. Further studies using Hydergine in the treatment of dementia appear to be justified.

[Source: http://www.lef.org/prod_hp/abstracts/hydergine.html]

Arch Neurol 1994 Aug;51(8):787-98
Overview of clinical trials of hydergine in dementia.
Schneider LS, Olin JT. Department of Psychiatry, University of Southern California School of Medicine, Los Angeles.

OBJECTIVE: To assess the overall effect of Hydergine (a combination drug called ergoloid mesylates) on patients with possible dementia and to investigate potential moderators of an effect. DATA SOURCES: MEDLINE, EMBASE, and two proprietary databases were searched for reports of clinical trials. STUDY SELECTION: Included were randomized, placebo-controlled, double-blind, parallel-group trials in subjects with symptoms consistent with dementia performed with specified outcome instruments and sufficient statistical information to calculate effect sizes. Forty-seven (31%) of 151 trials reviewed met selection criteria. DATA EXTRACTION: Potential moderating variables were extracted from each trial: sample size, inpatient-outpatient status, trial duration, age, gender, medication dose, publication year, and diagnostic grouping. Outcome measures were extracted with their associated statistics. DATA SYNTHESIS: The overall combined treatment effects ("adjusted d") for three types of outcome measures were calculated. Overall, Hydergine was more effective than placebo as assessed by comprehensive ratings (d = 0.47; 95% confidence interval [CI], 0.38 to 0.56; P = .0001), clinical global ratings (d = 0.56; 95% CI, 0.44 to 0.68; P = .0001), and combined neuropsychological measures (d = 0.27; 95% CI, 0.22 to 0.32; P = .0001). Inpatient status, daily doses of 4 mg or more, and vascular dementia were generally associated with larger effects. The effect in patients with possible Alzheimer's dementia was significant only for combined neuropsychological measures in five trials (d = 0.30; 95% CI, 0.16 to 0.44; P = .0001; and with a dose-response, P = .001). CONCLUSIONS: Overall, ergoloid mesylates were more effective than placebo. However, the effect in patients with possible Alzheimer's dementia was very modest at best. The dose-response relation suggests that potentially effective doses may be higher than the currently approved. The circumstances of the efficacy of Hydergine remain inadequately defined.

Tohoku J Exp Med 1990 Nov;162(3):225-33
Effects of co-dergocrine mesylate (Hydergine) in multi-infarct dementia as evaluated by positron emission tomography.

Nagasawa H, Kogure K, Kawashima K, Ido T, Itoh M, Hatazawa J. Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.

Three female patients aged from 74 to 79 with multi-infarct dementia were studied using positron emission tomography (PET) to assess the effect of co-dergocrine mesylate (Hydergine) on cerebral glucose metabolism. The cerebral glucose utilization (CMRGlc) of each patient was evaluated by PET scan using 2-deoxy-[18F]-2-fluoro-D-glucose (FDG). Following the first PET study, 0.04 mg/kg of co-dergocrine mesylate was injected intravenously with 250 ml saline solution, and then the second PET study was performed. The CMRGlc was determined from the images of the PET scan and the radioactivity of 18F in the plasma. After the administration of co-dergocrine mesylate, the value of CMRGlc increased significantly in the cerebral cortex (p less than 0.01 and p less than 0.05) and basal ganglia (p less than 0.05) compared with values before the administration, but no significant increase was found in the centrum semiovale. These results suggest that co-dergocrine mesylate stimulates glucose metabolism of neurons in the human brain.

Curr Med Res Opin 1989;11(8):491-500
Effects of intravenous high dose co-dergocrine mesylate ('Hydergine') in elderly patients with severe multi-infarct dementia: a double-blind, placebo-controlled trial.

Arrigo A, Casale R, Giorgi I, Guarnaschelli C, Zelaschi F. Universita degli Studi, Centro di Neurologia Clinica, Pavia, Italy.

A double-blind, placebo-controlled trial was carried out in 40 patients affected by multi-infarct dementia to see if a daily intravenous infusion of 3 mg co-dergocrine mesylate ('Hydergine') over 14 days would improve severely deteriorated elderly patients and shorten the latent period (3 months) which is observed when the drug is given orally. All the patients had severe mental impairment, psychological deficit or altered consciousness. A Hachinski score of 7 or more, and a cumulative score of at least 12 points on SCAG scale Items 1, 2 and 4 (anxiety/depression) and/or Items 5, 6 and 8 (alertness/confusion) were required for admission. After 1 week of intravenous infusion of placebo, patients were randomly allocated to treatment with co-dergocrine mesylate or placebo, from Day 1 to Day 14. The solutions were infused over a period of 2 hours. During the follow-up period from Day 15 to Day 21, the patients did not receive any treatment. Thirty-six patients (17 on co-dergocrine mesylate, 19 on placebo) completed the study. The results, as rated on the SCAG scale, indicated significant improvements, in favour of co-dergocrine mesylate, in cognitive dysfunction, mood depression, withdrawal and overall impression. Furthermore, the factor fatigue on the Nowlis scale and clinical global assessments by physicians also showed significant advantages of the co-dergocrine mesylate group over placebo. Nine out of 17 co-dergocrine mesylate patients complained of side-effects, usually experienced during infusion; they consisted mainly of nausea (6 patients), gastric discomfort (2 patients), and tremor, nasal congestion, flushing, hypotension and hypertension (1 patient each). Despite the appearance of side-effects, general tolerability was rated as 'good' by both physicians and patients. It is concluded, therefore, that intravenous high dose co-dergocrine mesylate treatment has a fast and clinically relevant effect on the key clinical symptoms of multi-infarct dementia.

J Am Geriatr Soc 1984 Aug;32(8):584-8
Double-blind clinical and psychologic study of ergoloid mesylates (Hydergine) in subjects with senile mental deterioration.

van Loveren-Huyben CM, Engelaar HF, Hermans MB, van der Bom JA, Leering C, Munnichs JM.

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.

J Am Geriatr Soc. 1981 Apr;29(4):164-71.
Senile dementia: combined pharmacologic and psychologic treatment.

Yesavage JA, Westphal J, Rush L.

Either supportive counseling (SC) or cognitive training (CT) was used in an attempt to enhance the efficiency of a standard pharmacologic treatment for dementia, viz, dihydroergotoxine mesylate (DEM, Hydergine). DEM was administered orally to 21 moderately demented subjects, in a dosage of 1 mg three times daily; and SC or CT was conducted for one hour every two weeks for a total of 12 weeks. The CT was designed to enhance memory and other intellectual functions by the teaching of organizational schemes and mnemonic devices. Outcome measurements included the Sandoz Clinical Assessment-Geriatric (SCAG), a behavioral rating scale measuring selected symptoms and signs of dementia; the Hamilton Rating Scale for Depression (HRSD); and the Buschke Selective Reminding Scale (BSRT), a psychometric test of memory and learning. The DEM + CT group of patients improved more than did the DEM + SC group for the measures of memory and learning (BSRT). However, no differences between groups were noted for the HRSD or SCAG behavioral measures.

Pharmacology 1978;16 Suppl 1:27-35
The clinical assessment of brain failure in the elderly.

McConnachie RW.

Dementia is a symptom complex probably arising from cerebral metabolic insufficiency. The testing of drugs thought to improve cerebral metabolism is difficult and many problems have to be overcome. Assessment of brain failure requires objective tests of intellect and memory. Subjective tests are used for disorders of personality and affect. The most useful and practical tests are described in detail. Clinical trials have to be double-blind with strict control of all factors which may influence the tests. Hydergine has been tested in 1,300 patients and shown to be an effective therapeutic agent.