A controlled trial of tacrine in alzheimer's disease

Martin Farlow, Stephen I. Gracon, Linda A. Hershey, Karen W. Lewis, Carl H. Sadowsky, Jann Dolan-Ureno

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Abstract

Objective.-To compare efficacy and safety of tacrine hydrochloride with placebo in patients with probable Alzheimer's disease. Design.-A 12-week, double-blind, placebo-controlled, parallel-group study. Setting.-Outpatients at 23 centers. Patients.-Men and women with probable Alzheimer's disease, at least 50 years old, mildly to moderately impaired, without other significant medical conditions. Interventions.-In the initial 6 weeks, patients received placebo, 20 mg/d of tacrine, or 40 mg/d of tacrine. In the second 6 weeks, half received the same treatment and half increased tacrine dose: those receiving placebo increased to 20 mg/d, those receiving 20 mg/d increased to 40 mg/d, and those receiving 40 mg/d increased to 80 mg/d. Primary Outcome Measures.-Alzheimer's Disease Assessment Scale (ADAS) cognitive component and clinician-rated Clinical Global Impression of Change (CGIC). Results.-Four hundred sixty-eight patients entered. After 12 weeks, dose-related improvement was significant on the ADAS cognitive (P=.014), clinician-rated CGIC (P=.014), and caregiver-rated CGIC (P=.006). Comparison of 80 mg/d with placebo showed significant improvement on the ADAS cognitive (P=.015), clinician-rated CGIC (P=.016), and caregiver-rated CGIC (P=.028). Significant effects appeared as early as 6 weeks on the ADAS cognitive and caregiver-rated CGIC. Among patients receiving 80 mg/d of tacrine, 51% achieved a four-point or greater improvement of the ADAS cognitive component after 12 weeks of treatment. Reversible asymptomatic transaminase elevations greater than three times normal occurred in 25% of patients. Other treatment-related events included nausea and/or vomiting (8%), diarrhea (5%), abdominal pain (4%), dyspepsia (3%), and rash (3%). Conclusions.-These results confirm the efficacy and safety of tacrine in some patients with Alzheimer's disease. After 12 weeks, the magnitude of the treatment effect is clinically important and recognized by the physician and caregiver. Liver toxicity is reversible and easily detected by weekly alanine aminotransferase determinations.

Original languageEnglish
Pages (from-to)2523-2529
Number of pages7
JournalJournal of the American Medical Association
Volume268
Issue number18
StatePublished - 1992

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Tacrine
Alzheimer Disease
Placebos
Caregivers
Safety
compound A 12
Dyspepsia
Therapeutics
Transaminases
Exanthema
Alanine Transaminase
Nausea
Abdominal Pain
Vomiting
Diarrhea
Outpatients
Outcome Assessment (Health Care)
Physicians
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Farlow, M., Gracon, S. I., Hershey, L. A., Lewis, K. W., Sadowsky, C. H., & Dolan-Ureno, J. (1992). A controlled trial of tacrine in alzheimer's disease. Journal of the American Medical Association, 268(18), 2523-2529.

A controlled trial of tacrine in alzheimer's disease. / Farlow, Martin; Gracon, Stephen I.; Hershey, Linda A.; Lewis, Karen W.; Sadowsky, Carl H.; Dolan-Ureno, Jann.

In: Journal of the American Medical Association, Vol. 268, No. 18, 1992, p. 2523-2529.

Research output: Contribution to journalArticle

Farlow, M, Gracon, SI, Hershey, LA, Lewis, KW, Sadowsky, CH & Dolan-Ureno, J 1992, 'A controlled trial of tacrine in alzheimer's disease', Journal of the American Medical Association, vol. 268, no. 18, pp. 2523-2529.
Farlow M, Gracon SI, Hershey LA, Lewis KW, Sadowsky CH, Dolan-Ureno J. A controlled trial of tacrine in alzheimer's disease. Journal of the American Medical Association. 1992;268(18):2523-2529.
Farlow, Martin ; Gracon, Stephen I. ; Hershey, Linda A. ; Lewis, Karen W. ; Sadowsky, Carl H. ; Dolan-Ureno, Jann. / A controlled trial of tacrine in alzheimer's disease. In: Journal of the American Medical Association. 1992 ; Vol. 268, No. 18. pp. 2523-2529.
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N2 - Objective.-To compare efficacy and safety of tacrine hydrochloride with placebo in patients with probable Alzheimer's disease. Design.-A 12-week, double-blind, placebo-controlled, parallel-group study. Setting.-Outpatients at 23 centers. Patients.-Men and women with probable Alzheimer's disease, at least 50 years old, mildly to moderately impaired, without other significant medical conditions. Interventions.-In the initial 6 weeks, patients received placebo, 20 mg/d of tacrine, or 40 mg/d of tacrine. In the second 6 weeks, half received the same treatment and half increased tacrine dose: those receiving placebo increased to 20 mg/d, those receiving 20 mg/d increased to 40 mg/d, and those receiving 40 mg/d increased to 80 mg/d. Primary Outcome Measures.-Alzheimer's Disease Assessment Scale (ADAS) cognitive component and clinician-rated Clinical Global Impression of Change (CGIC). Results.-Four hundred sixty-eight patients entered. After 12 weeks, dose-related improvement was significant on the ADAS cognitive (P=.014), clinician-rated CGIC (P=.014), and caregiver-rated CGIC (P=.006). Comparison of 80 mg/d with placebo showed significant improvement on the ADAS cognitive (P=.015), clinician-rated CGIC (P=.016), and caregiver-rated CGIC (P=.028). Significant effects appeared as early as 6 weeks on the ADAS cognitive and caregiver-rated CGIC. Among patients receiving 80 mg/d of tacrine, 51% achieved a four-point or greater improvement of the ADAS cognitive component after 12 weeks of treatment. Reversible asymptomatic transaminase elevations greater than three times normal occurred in 25% of patients. Other treatment-related events included nausea and/or vomiting (8%), diarrhea (5%), abdominal pain (4%), dyspepsia (3%), and rash (3%). Conclusions.-These results confirm the efficacy and safety of tacrine in some patients with Alzheimer's disease. After 12 weeks, the magnitude of the treatment effect is clinically important and recognized by the physician and caregiver. Liver toxicity is reversible and easily detected by weekly alanine aminotransferase determinations.

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