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. 1990 Feb 24;300(6723):495–499. doi: 10.1136/bmj.300.6723.495

Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. Groupe Français d'Etude de la Tetrahydroaminoacridine.

G Chatellier 1, L Lacomblez 1
PMCID: PMC1662308  PMID: 2107926

Abstract

OBJECTIVE--To see whether combined treatment with oral tacrine (tetrahydroaminoacridine; THA) and lecithin improves the symptoms of patients with Alzheimer's disease. DESIGN--Multicentre double blind, placebo controlled, random order crossover trial with individual determination of maximum tolerated dosage and four month follow up. SETTING--Outpatient departments at six university neurological centres. PATIENTS--67 Outpatients (24 men, 43 women) aged 53-81 (mean 66 (SD 7.3)) selected according to the following criteria: probable Alzheimer's disease as defined by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; absence of mood disorder; mini mental state score lower than 26; availability of a close relative able to complete questionnaires; and informed consent of the patient or his or her closest relative, or both. INTERVENTIONS--Mean of 114 mg tacrine or placebo daily plus 1200 mg lecithin daily given in three divided doses for one four week active treatment period and one four week control period without washout at crossover. MAIN OUTCOME MEASURES--Cognitive state as assessed by Folstein's mini mental state rating scale, behavioural state as assessed by the Stockton geriatric rating scale, and overall state as assessed with a visual analogue scale rated by both the relative and the physician. RESULTS--Compared with placebo tacrine did not improve either the mini mental state score (mean 14.9 (SD 7.3) v 14.8 (7.3)) or the Stockton geriatric score (28.2 (15.7) v 28.7 (17.8)), but a slight and statistically significant improvement occurred in the physician's score on the visual analogue scale (6.3 (10.2) v 11.6 (17.9)). Seven patients dropped out. Six patients were excluded because of acute hepatitis and one withdrew for personal reasons not related to treatment. Two other patients developed acute hepatitis at the end of the eight week crossover trial and another during the follow up study. Twenty patients complained of gastrointestinal side effects. CONCLUSIONS--Neither short term nor long term treatment with oral tacrine at dosages lower than 125 mg/day improves the symptoms of Alzheimer's disease. Moreover, these dosages may induce hepatitis (nine of 67 patients in this series).

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Selected References

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  1. Ames D. J., Bhathal P. S., Davies B. M., Fraser J. R. Hepatotoxicity of tetrahydroaminoacridine. Lancet. 1988 Apr 16;1(8590):887–887. doi: 10.1016/s0140-6736(88)91636-4. [DOI] [PubMed] [Google Scholar]
  2. Folstein M. F., Folstein S. E., McHugh P. R. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6. [DOI] [PubMed] [Google Scholar]
  3. Hachinski V. C., Iliff L. D., Zilhka E., Du Boulay G. H., McAllister V. L., Marshall J., Russell R. W., Symon L. Cerebral blood flow in dementia. Arch Neurol. 1975 Sep;32(9):632–637. doi: 10.1001/archneur.1975.00490510088009. [DOI] [PubMed] [Google Scholar]
  4. Hills M., Armitage P. The two-period cross-over clinical trial. Br J Clin Pharmacol. 1979 Jul;8(1):7–20. doi: 10.1111/j.1365-2125.1979.tb05903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kaye W. H., Sitaram N., Weingartner H., Ebert M. H., Smallberg S., Gillin J. C. Modest facilitation on memory in dementia with combined lecithin and anticholinerestase treatment. Biol Psychiatry. 1982 Feb;17(2):275–280. [PubMed] [Google Scholar]
  6. Little A., Levy R., Chuaqui-Kidd P., Hand D. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1985 Aug;48(8):736–742. doi: 10.1136/jnnp.48.8.736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Marx J. L. Alzheimer's drug trial put on hold. Science. 1987 Nov 20;238(4830):1041–1042. doi: 10.1126/science.3317822. [DOI] [PubMed] [Google Scholar]
  8. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
  9. Meer B., Baker J. A. The Stockton Geriatric Rating Scale. J Gerontol. 1966 Jul;21(3):392–403. doi: 10.1093/geronj/21.3.392. [DOI] [PubMed] [Google Scholar]
  10. Montgomery S. A., Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382–389. doi: 10.1192/bjp.134.4.382. [DOI] [PubMed] [Google Scholar]
  11. Penn R. D., Martin E. M., Wilson R. S., Fox J. H., Savoy S. M. Intraventricular bethanechol infusion for Alzheimer's disease: results of double-blind and escalating-dose trials. Neurology. 1988 Feb;38(2):219–222. doi: 10.1212/wnl.38.2.219. [DOI] [PubMed] [Google Scholar]
  12. Perry E. K., Tomlinson B. E., Blessed G., Bergmann K., Gibson P. H., Perry R. H. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J. 1978 Nov 25;2(6150):1457–1459. doi: 10.1136/bmj.2.6150.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pocock S. J., Hughes M. D., Lee R. J. Statistical problems in the reporting of clinical trials. A survey of three medical journals. N Engl J Med. 1987 Aug 13;317(7):426–432. doi: 10.1056/NEJM198708133170706. [DOI] [PubMed] [Google Scholar]
  14. Summers W. K., Majovski L. V., Marsh G. M., Tachiki K., Kling A. Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N Engl J Med. 1986 Nov 13;315(20):1241–1245. doi: 10.1056/NEJM198611133152001. [DOI] [PubMed] [Google Scholar]
  15. Wilcock G. K., Surmon D., Forsyth D., Morgan R. Cholinergic side-effects of tetrahydroaminoacridine. Lancet. 1988 Dec 3;2(8623):1305–1305. doi: 10.1016/s0140-6736(88)92909-1. [DOI] [PubMed] [Google Scholar]

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