The efficacy and toxicity of tacrine have been debated since dramatic improvement of cognition in patients with Alzheimer's disease after treatment with tacrine was reported in 1986.1 The scientific validity of this study was contested2 and cases of hepatotoxicity were reported3,4; the first major trial of tacrine was suspended after 2 months.5 In an attempt to reduce toxicity, the design of several large trials6-8 incorporated a lower maximum dosage (usually 80 mg/d), but results demonstrated considerably smaller benefits still accompanied by significant adverse effects and high drop-out rates.
See also pp 985 and 992.
In this issue of THE JOURNAL, Knapp et al9 report the first large randomized controlled study to use a higher dosage of tacrine (maximum dosage, 160 mg/d) in a 30-week trial. Although hepatotoxicity and adverse effects produced high dropout rates, the results eventually led to Food and Drug Administration approval
Winker MA. Tacrine for Alzheimer's DiseaseWhich Patient, What Dose?. JAMA. 1994;271(13):1023-1024. doi:10.1001/jama.1994.03510370075036