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. 2000;2000(2):CD000359.
doi: 10.1002/14651858.CD000359.

Hydergine for dementia

J Olin  1 , L Schneider, A Novit, S Luczak
Affiliations

Hydergine for dementia

J Olin et al. Cochrane Database Syst Rev. 2000.

Update in

  • Hydergine for dementia.
    Olin J, Schneider L, Novit A, Luczak S. Olin J, et al. Cochrane Database Syst Rev. 2001;(2):CD000359. doi: 10.1002/14651858.CD000359. Cochrane Database Syst Rev. 2001. PMID: 11405961

Abstract

Background: Currently hydergine is used almost exclusively for treating patients with either dementia, or 'age-related' cognitive symptoms. Since the early eighties there have been over a dozen more clinical trials, yet hydergine's efficacy remains uncertain. Although previous reviews offer generally favorable support for hydergine's efficacy, they were, however, limited by a bias with respect to the particular clinical studies chosen (eg, the inclusion of case reports, and uncontrolled trials), and by authors' impressionistic assessments of results. Not surprisingly, there has been a lack of consensus among reviewers with regard to the efficacy of hydergine. In 1994, a meta-analysis was published by the present reviewers who reported that overall, hydergine was more effective than placebo. However they also observed that the statistical evidence for efficacy in 'possible or probable Alzheimer's disease' patients was so modest that one additional statistically non-significant trial would have reduced the results to non significance.

Objectives: Because of uncertainty surrounding the efficacy of hydergine, the goals of this overview were to assess its overall effect in patients with possible dementia, and to investigate potential moderators of an effect.

Search strategy: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'hydergine', 'ergoloids,' 'ergoloid mesylates,' 'dihydroergocristine,' 'dihydroergocryptine,' 'dihydroergotoxine,' and 'dihydroergocornine. MEDLINE, EMBASE, and two proprietary databases were searched also. Published reviews were inspected for further sources.

Selection criteria: Trials to be included must be randomized, double-blind, parallel-group, and unconfounded comparisons of hydergine with placebo for a treatment duration of greater than 1 week in subjects with dementia or symptoms consistent with dementia.

Data collection and analysis: Data were extracted independently by the reviewers, pooled where appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. Outcomes of interest included clinical global impressions of change and comprehensive rating scales. Potential moderating variables of a treatment effect included: inpatient/outpatient status, trial duration, age, sex, medication dose, publication year, and diagnostic grouping.

Main results: There were a total of nineteen trials that met inclusion criteria and that had data sufficient for analysis. Thirteen trials reported sufficient information to use a global rating of improvement and nine trials provided information on a comprehensive rating scale. Three trials provided both outcome measures. It was not possible to use many of the published results in a combined analysis owing to the lack of sufficient data to perform statistical analyses. For the twelve trials that used global ratings, there was a significant effect favoring hydergine (OR 3.78, 95%CI, 2.72-5.27). For the nine trials that used comprehensive ratings, there was a significant mean difference favoring hydergine (WMD 0.96, 95%CI, 0. 54-1.37). Hydergine was well tolerated in these trials, with 78% of randomized subjects available for data analyses. Greater effect sizes on global ratings were associated with younger age, and possibly higher dose, although most of the subgroup analyses were statistically insignificant.

Reviewer's conclusions: 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 modera

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Conflict of interest statement

The authors (JO, LS) were involved in a previous meta‐analysis of this literature that was commissioned by Sandoz Pharmaceuticals Corporation (now Novartis).

Figures

1.1
1.1. Analysis
Comparison 1 Hydergine versus Placebo: Global Rating (% improved), Outcome 1 Patient status.
1.2
1.2. Analysis
Comparison 1 Hydergine versus Placebo: Global Rating (% improved), Outcome 2 Diagnosis.
1.3
1.3. Analysis
Comparison 1 Hydergine versus Placebo: Global Rating (% improved), Outcome 3 Mean Age.
1.4
1.4. Analysis
Comparison 1 Hydergine versus Placebo: Global Rating (% improved), Outcome 4 Gender.
1.5
1.5. Analysis
Comparison 1 Hydergine versus Placebo: Global Rating (% improved), Outcome 5 Treatment length (weeks).
1.6
1.6. Analysis
Comparison 1 Hydergine versus Placebo: Global Rating (% improved), Outcome 6 Mean Daily Dose.
1.7
1.7. Analysis
Comparison 1 Hydergine versus Placebo: Global Rating (% improved), Outcome 7 Publication year.
2.1
2.1. Analysis
Comparison 2 Hydergine versus Placebo: Comprehensive Rating, Outcome 1 Patient status.
2.2
2.2. Analysis
Comparison 2 Hydergine versus Placebo: Comprehensive Rating, Outcome 2 Diagnosis.
2.3
2.3. Analysis
Comparison 2 Hydergine versus Placebo: Comprehensive Rating, Outcome 3 Mean Age.
2.4
2.4. Analysis
Comparison 2 Hydergine versus Placebo: Comprehensive Rating, Outcome 4 Gender.
2.5
2.5. Analysis
Comparison 2 Hydergine versus Placebo: Comprehensive Rating, Outcome 5 Treatment length (weeks).
2.6
2.6. Analysis
Comparison 2 Hydergine versus Placebo: Comprehensive Rating, Outcome 6 Mean Daily Dose.
2.7
2.7. Analysis
Comparison 2 Hydergine versus Placebo: Comprehensive Rating, Outcome 7 Publication year.
See this image and copyright information in PMC

References

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Kaiser 1956 {published data only}
    1. Kaiser G, Tschabitscher H. Erfahrungen mit Hydergin in der Behandlung zerebraler Durchblutungsstorungen im hoheren [Erfahrungen mit Hydergin in der Behandlung zerebraler Durchblutungsstorungen im hoheren]. Alter. Wien. Klin. Wschr. 1956;68:150‐4. - PubMed
Kanowski 1988 {published data only}
    1. Kanowski S, Fischhof P, Hiersemenzel R, Rohmel J, Kern U. Therapeutic efficacy of nootropic drugs ‐ a discussion of clinical phase III studies with Nimodipine as a model. Zeitschrift fur Gerontopsychologie und ‐psychiatrie 1988;1:35‐44.
Klein 1985 {published data only}
    1. Klein L, Cohen VJ. Insuficiencia cerebrovascular su tratamiento con dihidroergotoxina, 4.5mg [Insuficiencia cerebrovascular su tratamiento con dihidroergotoxina, 4.5mg]. Sem. Med 1985;167:189‐95.
Koberle 1984 {published data only}
    1. Koberle S, Spiegel R. A long‐term study with co‐dergocrine mesylate (Hydergine) in healthy pensioners ‐ Results after 3 years. Gerontology (Basel) 1984;30:3‐52. - PubMed
Kugler 1978 {published data only}
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Kugler 1985 {published data only}
    1. Kugler VJE, Meurer‐Krull BCh. mesylate] [Electroencephalography and psychometric measurements during the treatment of cerebral insufficiency with nicergoline and dihydroergotamine mesylate] Electroencephalography and psychometric measurements during the treatment of cerebral insufficiency with nicergoline and dihydroergotamine mesylate] mesylate] [Elektroenzephalographische und psychometrische messungen bei der behandlung der zerebralen insuffizienz mit Nicergolin und Dihydroergotoxin‐Mesylat]. Arzneimittel‐Forsch 1985;35:1865‐70. - PubMed
Kuskowski 1990 {published data only}
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Labecki 1954 {published data only}
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Ladurner 1991 {published data only}
    1. Ladurner G, Erhart P, Erhart C, Scheiber V. Therapy of organic brain syndrome with nicergoline given once a day. ORIGINAL TITLE: Therapie des hirnorganischen Psychosyndroms mit Nicergolin in taglicher Einmalgabe.. Wien‐Klin‐Wochenschr 1991;103(1):8‐14. - PubMed
Li 2004 {published data only}
    1. Li H, Liu F, Xu LR. Effect of huannao yicong capsule on senile mild cognitive impairment. Chinese Journal of Integrated Traditional and Western Medicine 2004;24(8):689‐93. - PubMed
Liao 2004 {published data only}
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Linden 1975 {published data only}
    1. Linden ME. Mental decline in elderly patients. Scientific exhibit, National Association of Private Psychiatric Hospitals, Palm Springs, CA 1976.
    1. Linden ME. Retirement and the elderly patients. Problems and practical therapy. Scientific Exhibit, American Geriatrics Society, 32nd Annual Meeting, Miami Beach, FL 1975; Vol. 4:16‐17.
Linden 1976 {published data only}
    1. Linden ME. Mental decline in elderly patients. Scientific exhibit, National Association of Private Psychiatric Hospitals, Palm Springs, CA 1976.
Linder 1977 {published data only}
    1. Linder L, Irfan S. Hydergine in the treatment of geriatric patients suffering from senile mental deterioration. VIth World Congress of Psychiatry, Honolulu, HI. Washington, DC: American Psychiatric Association., 1977; Vol. 1025:188.
Liu 2005 {published data only}
    1. Liu XD, Wan Q, Wei D, Wang XM. Cognitive and non‐cognitive functions in patients with vascular dementia and the interventional efficacy of dihydroergotamine mesilate plus nimodipine. Chinese Journal of Clinical Rehabilitation 2005;9(20):48‐9.
Lozeron 1974 {published data only}
    1. Lozeron H. Cerebral circulatory disorders and arteriosclerosis. Their treatment with Hydergine [Troubles circulatoires cerebraux et arteriosclerose. Leur traitement par l'Hydergine]. Praxis 1974;63:660‐5. - PubMed
Luo 2001 {published data only}
    1. Luo ZG, Zhou WQ, Gao P. Clinical observation on effect of Xianlong capsule in treating vascular dementia. Chinese Journal of Integrated Traditional and Western Medicine 2001;21(8):565‐8. - PubMed
Mars 1970 {published data only}
    1. Mars G, Nebuloni G. Treatment of cerebral vascular insufficiency syndromes in old age. Controlled research by double blind technique [Sul trattamento delle sindromi da insufficienza cerebrale vascolare nell'eta avanzata]. G. Geront 1970;18:153‐76. - PubMed
Martucci 1986 {published data only}
    1. Martucci N, Manna V, Mailand F. EEG‐Pharmacological and neuropsychological study of Dihydroergocristine Mesylate in patients with chronic cerebrovascular disease. Advances in Therapy 1986;3:210‐23.
Matejcek 1979 {published data only}
    1. Matejcek M, Knor K, Piguet PV, Weil C. Electroencephalographic and clinical changes as correlated in geriatric patients treated three months with an ergot alkaloid preparation. Journal of the American Geriatrics Society 1979;27:198‐202. - PubMed
Matejcek 1980 {published data only}
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Matejcek 1986 {published data only}
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McConnachie 1978 {published data only}
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McDonald 1979 {published data only}
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McDonald 1989 {unpublished data only}
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Mellini 1973 {published data only}
    1. Mellini M. Clinical use of a new vasoactive drug: Nicergoline [Considerazioni sull'impiego clinico di un nuovo farmaco vasoattivo: la nicergolina]. Minerva Med. 1973;64:1844‐53. - PubMed
Memin 1973 {published data only}
    1. Memin Y, Hueber EN. Double‐blind study according to a quantitative scale of evaluation of a treatment for chronic cerebrovascular disorders [Etude a double insu selon une echelle d'appreciation quantitative d'un traitement des troubles vasculaires cerebraux chroniques]. Entretiens de Bichat 1973;Vol. Expansion Scientif. Francais, Paris:239‐42.
Misra 1982 {published data only}
    1. Misra SC, Patnaik BC, Patnaik SR, Panda RK, Maharana SN. Dehydroergotoxine mesylate (Hydergine) in cerebrovascular insufficiency (Summary). J. Assoc. Physicians India 1982;30:696.
Misurec 1978 {published data only}
    1. Misurec J, Moravek Z, Nahunek K, Ceskova E, Slama B, Svestka J. DH ergotoxin (Spofa) sublingual tablets in the treatment of cerebrovascular insufficiency in involution: clinical and experimental psychologic study. Act. Nerv. Sup. (Praha) 1978;20:266‐7. - PubMed
Moglia 1983 {published data only}
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Nelson 1973 {unpublished data only}
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Nelson 1975 {published data only}
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Nicrosini 1976 {published data only}
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Novo 1978 {published data only}
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Odanische 1981 {published data only}
    1. Odanische D, Eisinger JM. [Estudio comparative doble ciego/cruzado de la asociacion vincamina‐pracetam frente a la dihidroergotoxina en la insuficiencia vascular cerbral]. ed. Klin. (Ed. Esp.) 1981;21:24‐31.
Olivella 1981 {published data only}
    1. Olivella J, Espadaler JM. Estudio comparativo doble ciego/cruzado de la asociacion vincamina‐piracetam frente a la dihidroergotoxina en la insuficiencia vascular cerebral [Estudio comparativo doble ciego/cruzado de la asociacion vincamina‐piracetam frente a la dihidroergotoxina en la insuficiencia vascular cerebral]. Med. Klin. (ed. Esp) 1981;21:24‐31.
Orma 1956 {published data only}
    1. Orma EJ. Hydrogenated ergot alkaloids (Hydergine) in the treatment of geriatric postural dizziness. Ann. Med. Int. Fenniae 1956;45:39. - PubMed
Oswald 1979 {published data only}
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Oswald 1980 {published data only}
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Oswald 1982 {published data only}
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Ouaniche 1981 {published data only}
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Parade 1978 {published data only}
    1. Parade D. Therapie bei kardialer und zerebraler insuffizienz: Ergebnisse einer vergleichenden doppelblindprufung [Therapie bei kardialer und zerebraler insuffizienz: Ergebnisse einer vergleichenden doppelblindprufung]. Aerztl. Prax 1978;30:2783‐5.
Patin 1981 {unpublished data only}
    1. Patin J, Hamot HB. A double‐blind placebo‐controlled, multi‐clinic study to evaluate the safety and efficacy of a total daily dose of 6.0 mg of Hydergine for the treatment of cognitive, affective and behavioral symptoms associated with aging. Unpublished manuscript: Statistical report for Sandoz Pharmaceutical Research and Development 1981.
Paux 1975 {published data only}
    1. Paux G, Boismare F, Delaunay P. Double‐blind study with Hydergine in the elderly subject [Etude en double aveugle de l'Hydergine chez le sujet age]. Nouv. Presse. Med. 1975;4:2529. - PubMed
Pfeiff 1980 {published data only}
    1. Pfeiff E, Schlegel HE, Seus R, Dennler HJ, Kugler J. Therapy of organic psychosyndrome with hydergine and digitalis. A component study using double blind technics [Therapie des hirnorganischen psychosyndroms mit Hydergin und digitalis. Eine komponentenstudie in doppelblindtechnik]. Med. Welt. (Stuttg) 1980;31:1403‐7. - PubMed
Piguet 1981 {published data only}
    1. Piguet PV, Zoufal Z. Controlled double‐blind study on the clinical equivalence of 2 Hydergine dosage regimens: 1 x 4.5mg compared to 3 x 1.5mg per day [Etude controlee en double insu de l'equivalence clinique de deux regimes posologiques d'Hydergine: 1 x 4.5mg compare a 3 x 1.5mg par jour]. Rev. Med. Suisse Rom. 1981;101:157‐63. - PubMed
PiresDeOliveira 1973 {published data only}
    1. Pires De Oliveira RS. Electroencephalographic alterations after administration of vaso‐active substance (Hydergine) [Alteracoes Eletrencefalograficas apos administracao de substancias Vaso‐Ativas (Hydergine)]. Arch. Neuro‐psiquiat. 1973;31:107‐22. - PubMed
Pomara 1983 {published data only}
    1. Pomara N, Block R, Abraham J, Domino EF, Gershon S. Combined cholinergic precursor treatment and dihydroergotoxine mesylate in Alzheimer's disease. IRCS Med. Sci: Psychology and Psychiatry 1983;11:1048‐9.
Popkin 1956 {published data only}
    1. Popkin RJ. The hydrogenated alkaloids of ergot (Hydergine) in geriatrics ‐ follow up study. American Pract. Digest Treatment 1956;7:1594‐7. - PubMed
Puxty 1989 {published data only}
    1. Puxty J. Community screening for dementia and evaluation of treatment. In: Carlsson A, Kanowski S, Allain H, Spiegel R editor(s). Proceedings of a Symposium Basle (CH). Basil, Switzerland: Parthenon Publishing Group, 1989:211‐230.
Puxty 1991 {published data only}
    1. Puxty J. High‐dose Ergoloid Mesylates (Hydergine) in community residing patients with age‐related mental decline. 7th submission to the Journal of the American Geriatric Association 1991.
Pöpperl 2004 {published data only}
    1. Pöpperl G, Tatsch K, Ruzicka E, Storch A, Gasser T, Schwarz J. Comparison of alpha‐dihydroergocryptine and levodopa monotherapy in Parkinson's disease: assessment of changes in DAT binding with [123I]IPT SPECT. Journal of Neural Transmission 2004;111(8):1041‐52. - PubMed
Rao 1972 {published data only}
    1. Rao DB, Norris JR. A double‐blind investigation of Hydergine in the treatment of cerebrovascular insufficiency in the eldery. Hopkins Med. J. 1972;130:317‐24. - PubMed
Rehman 1973a {published data only}
    1. Rehman SA. Two trials comparing Hydergine with placebo in the treatment of patients suffering from cerebrovascular insufficiency. Current Medical Research and Opinion 1973;1:456‐62. - PubMed
Rehman 1973b {published data only}
    1. Rehman SA. Two trials comparing Hydergine with placebo in the treatment of patients suffering from cerebrovascular insufficiency. Current Medical Research and Opinion 1973;1:456‐62. - PubMed
Riccardi 1978 {published data only}
    1. Riccardi T, Passeri F, Locatelli F. Controlled clinical study of the effects of Anasclerol in hospitalized patients with cerebrovascular disorders [Studio clinico controllato sugli effetti dell'Anasclerol in pazienti cerebro‐vasculopatici ospedalizzati]. Minerva Med. 1978;69:2873‐8. - PubMed
Ronge 1982 {published data only}
    1. Ronge J, Dennler HJ. Comparison of subjective tolerance of hydergine specific and hydergine in gerontologic therapy [Vergleich der subjektiven vertraglichkeit von Hydergin spezial und Hydergin in der gerontotherapie]. Med. Welt. (Stuttg) 1982;33:1485‐9. - PubMed
Rosen 1975 {published data only}
    1. Rosen HJ. Mental decline in the elderly: Pharmacotherapy (Ergot Alkaloids versus Papaverine). J. Amer. Geriat. Soc. 1975;23:169‐174. - PubMed
Roubicek 1971 {published data only}
    1. Roubicek J, Geiger C, Abt K. Hydergine therapy in geriatric patients. VIth European Congress of Clinical Gerontology. Berne, Switzerland, abstract no.89 1971.
    1. Roubicek J, Geiger C, Abt K. Hydergine therapy in geriatric patients. 5th World Congress of Psychiatry, Mexico. American Psychiatric Association, 1971:501.
Roubicek 1972 {published data only}
    1. Roubicek J, Geiger CH, Abt K. An ergot alkaloid preparation (Hydergine) in geriatric therapy. Journal of the American Geriatrics Society 1972;5:222‐9. - PubMed
Roubicek 1973 {published data only}
    1. Roubicek J, Geiger CH, Abt K, Huber F. Hydergine therapy in geriatric patients. In: Steinmann B, Huber H editor(s). Proceedings of the VI European Congress of Clinical Gerontology. Berne, Switzerland: Verlag, 1973:468‐81.
    1. Roubicek J, Huber F. Influence des alcaloides hydrogenes de l'ergot sur la fonction cerebrale dans la vieillesse [Influence des alcaloides hydrogenes de l'ergot sur la fonction cerebrale dans la vieillesse]. In: Geraud J, Lazorthes G, Bes A editor(s). L'ischemie cerebrale dans la territoire carotidien. Journees internationales de circulation cerebrales. Toulouse, France: Revue de Medecine de Toulouse, 1973:509‐13.
Roubicek 1975 {published data only}
    1. Roubicek J. Hydergina en la terapia geriatrica [Hydergina en la terapia geriatrica]. Invest. Medica Internacional 1975;2:61‐71.
Saletu 1990 {published data only}
    1. Saletu B, Grunberger J, Anderer R. On brain protection of co‐dergocrine mesylate (Hydergine) against hypoxic hypoxidosis of different severity: double‐blind placebo‐controlled quantitative EEG and psychometric studies. Int J Clin Pharmacol Ther Toxicol. 1990;28(12):510‐524. - PubMed
Saletu 1994 {published data only}
    1. Saletu B, Grunberger J, Anderer P, Linzmayer L, Pakesch G, Zyhlarz G. Effect‐kinetics on brain protection of two codergocrine‐mesylate preparations (Aramexe retard registered and Hydergine registered) by EEG mapping and psychometry under hypoxia. Archives of Gerontology and Geriatrics 1994;18(2):81‐99. - PubMed
Samorajski 1982 {published data only}
    1. Samorajski T, Ho BT, Kralik PM, Hartford JT. Serum prolactin changes with age, senile dementia, and dihydroergotoxine mesylate treatment. In: Giacobini E, Filogamo G, Giacobini G, Vernadakis A editor(s). Aging: Aging Brain. Cellular and Molecular Mechanisms of Aging in the Nervous System. Vol. 20, New York: Raven Press, 1982:259‐69.
Schardt 1982 {published data only}
    1. Schardt F, Dennler HJ. Behandlung des hochdrucks im alter mit Hydergin [Behandlung des hochdrucks im alter mit Hydergin]. Therapiewoche 1982;32:4039‐40, 4042‐3, 4046‐7.
Schartl 1978 {published data only}
    1. Schartl W, Bratke G, Kemper R. Uber die wirkung von Card‐Hydergin in doppelblindversuch [Uber die wirkung von Card‐Hydergin in doppelblindversuch]. Therapiewoche 1978;28:9117‐8, 9120, 9123‐6.
Schneider 1994 {published data only}
    1. Schneider LS, Olin JT. Overview of clinical trials of hydergine in dementia. Archives of Neurology 1994;51(8):787‐798. - PubMed
Schnell 1967 {published data only}
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Setnikar 2001 {published data only}
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Seus 1969 {published data only}
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Shoptaw 2005 {published data only}
    1. Shoptaw S, Watson DW, Reiber C, Rawson RA, Montgomery MA, Majewska MD, et al. Randomized controlled pilot trial of cabergoline, hydergine and levodopa/carbidopa: Los Angeles Cocaine Rapid Efficacy Screening Trial (CREST). Addiction 2005;100(Suppl):178‐90. - PubMed
Soni 1975 {published data only}
    1. Soni SD, Soni SS. Dihydrogenated alkaloids of ergotoxine in non‐hospitalised elderly patients. Curr. Med. Res. Opinion. 1975;3:464‐8.
Spiegel 1983 {published data only}
    1. Spiegel R, Huber F, Koberle S. A controlled long‐term study with ergoloid mesylates (Hydergine) in healthy, elderly volunteers: results after three years. Journal of the American Geriatrics Society 1983;31:549‐55. - PubMed
Spilich 1996 {published data only}
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Stewart 1996 {published data only}
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Strauss 1951 {published data only}
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Strauss 1954 {published data only}
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Tartara 1974 {published data only}
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Tecce 1981 {published data only}
    1. Tecce JJ, Boehner MB, Cattanach L, Branconnier R, Cole JO. Hydergine treatment and brain‐functioning (CNV rebound) in Alzheimer's patients: preliminary findings. Psychoparmacology Bulletin 1981;17:202‐6.
Tecce 1983a {published data only}
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Tecce 1983b {published data only}
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Teixeira 1970 {published data only}
    1. Teixeira JE. Hydergine in symptomatic treatment of cerebrovascular insufficiency. Comparative study with placebo [Hydergine no tratamento sintomatico da insuficiencia vascular cerebral. Ensaio clinico comparativo con placebo]. Hospital 1970;77:1907‐31. - PubMed
Thibault 1974 {published data only}
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Thienhaus 1987 {published data only}
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Tinklenberg 1986 {unpublished data only}
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Triboletti 1969 {published data only}
    1. Triboletti F, Ferri H. Hydergine for treatment of symptoms of cerebrovascular insufficiency. Current Therapeutic Research 1969;11:609‐20. - PubMed
Tucker 1982 {published data only}
    1. Tucker JS. An assessment of the effect of intramuscular Hydergine in elderly patients with early dementia using critical flicker fusion thresholds. British Journal of Clinical Practice 1982;16:16‐17.
Winslow 1974 {unpublished data only}
    1. Winslow IE. The hospitalized geriatric patient: Guidelines for effective therapy. Presented at the Scientific Exhibit, American Medical Association, 28th Clinical Convention, Portland, Oregon. 1974:1‐24.
Yan 2001 {published data only}
    1. Yan XP, Wang H, Zhang TZ. Clinical observation of effect on tongmai yizhi capsule in treating vascular dementia. Chinese Journal of Integrated Traditional and Western Medicine 2001;21(8):573‐5. - PubMed
Yesavage 1979 {published data only}
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Yesavage 1981b {published data only}
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Yoshikawa 1983 {published data only}
    1. Yoshikawa M, Hirai S, Aizawa T, Kuroiwa Y, Goto F, Sofue I, Toyokura Y, Yamamura H, Iwasaki Y. A dose‐response study with Dihydroergotoxine Mesylate in cerebrovascular disturbances. Journal of the American Geriatrics Society 1983;31:1‐7. - PubMed
Zhao 1999 {published data only}
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References to studies awaiting assessment

Klebel 1992 {published data only}
    1. Klebel E, Hutter M, Maritsch F. The influence of co‐derogocrine mesilate (hydergine FAS) on psychometric performance of elderly patients with organic brain syndrome. Zeitschrift Fur Gerontolgie and Psychiatrie 1992;5(1):43‐55.

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