A controlled trial of tacrine in Alzheimer's disease. The Tacrine Study Group.
OBJECTIVE
To compare efficacy and safety of tacrine hydrochloride with placebo in patients with probable Alzheimer's disease.


METHODS
A 12-week, double-blind, placebo-controlled, parallel-group study.


METHODS
Outpatients at 23 centers.


METHODS
Men and women with probable Alzheimer's disease, at least 50 years old, mildly to moderately impaired, without other significant medical conditions.


METHODS
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.


METHODS
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.
Farlow
M
M
Center for Alzheimer's Disease and Related Disorders, Indiana University Medical Center, Indianapolis.
Gracon
S I
SI
Hershey
L A
LA
Lewis
K W
KW
Sadowsky
C H
CH
Dolan-Ureno
J
J
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D013619:Tacrine / Q000627:therapeutic use*; D016896:Treatment Outcome
D013619:Tacrine