Effectiveness of hypnotic drugs with prolonged use: Flurazepam and pentobarbital

This study represents the first attempt to rigorously evaluate the effectiveness of hypnotic drugs under conditions of prolonged use. Flurazepam, 30 mg, and pentobarbital, 100 mg, were separately evaluated in identical 47-night sleep laboratory drug evaluation studies on insomniac subjects, which included 4 weeks of drug administration. Flurazepam was found to be effective in inducing and maintaining sleep over all treatment conditions. With long-term use, only a slight loss of effectiveness was suggested. Flurazepam also produced a moderate decrease in REM sleep and marked decrease in eye movement density and stage 4 sleep with short- and intermediate-term use. While the decreases in both REM sleep and eye movement density lessened with long-term use, stage 4 sleep remained markedly suppressed. No rebound was noted in any of these parameters after withdrawal. Pentobarbital was found to be effective in inducing and maintaining sleep only with short-term drug administration. This strongly suggests that it is of limited value for insomniac patients who require nightly medication beyond short-term use. Pentobarbital caused a minimal decrease in REM sleep with short- and intermediate-term administration, and slight rebound following withdrawal. Stages 3 and 4 sleep were decreased with short-term use and increased above baseline levels after withdrawal.