Tolerance and Rebound During and After Short-term Administration of Quazepam, Triazolam and Placebo to Healthy Human Volunteers

Abstract

Quazepam 15 mg, triazolam 0.25 mg and placebo were administered to 12 healthy volunteers. Each drug was given for 14 nights using a balanced design with at least 28 days between drug administrations. A test battery of physiological, psychological and subjective measures was administered on the mornings of days 1, 8, 14, 15 and 22 of the drug and post-drug periods. Seven days prior to and on days 1 to 28 of the drug and post-drug periods, sleep and self evaluation questionnaires were completed. Quazepam was associated with definite EEG effects, an unexpected improvement in simple motor performance and an increase in several bodily symptoms and ratings of sedation. Triazolam-impaired performance and also increased ratings of bodily symptoms and sedation. Two symptom increases with triazolam--metallic taste and touch sensitivity--might reflect day-time rebound. Sleep quality was improved by both drugs. There was little evidence of tolerance to drug effects on EEG or psychomotor tests. However tolerance was seen to the bodily symptoms and mood ratings. Rebound after drug discontinuation was not convincingly detected.