PHARMACODYNAMICS OF TEMAZEPAM IN PRIMARY INSOMNIA - ASSESSMENT OF THEVALUE OF QUANTITATIVE ELECTROENCEPHALOGRAPHY AND SACCADIC EYE-MOVEMENTS IN PREDICTING IMPROVEMENT OF SLEEP

Background and objective: Quantitative electroencephalographic paramet ers and saccadic eye movements are frequently used as pharmacodynamic measures of benzodiazepine effect. We investigated the relationship be tween these measures and the hypnotic effect. Methods: The correlation between the pharmacodynamic measures and sleep quality was determined in 21 patients with primary insomnia, The pharmacokinetic-pharmacodyn amic relationships were characterized after administration of 20 mg or al temazepam, The hypnotic effect was determined on the basis of polys omnographic sleep recordings and a subjective sleep evaluation questio nnaire, Correlations between pharmacodynamic measures and the improvem ent of sleep were investigated. Results: The pharmacokinetic-pharmacod ynamic relationships for the parameters derived from electroencephalog raphy and saccadic eye movements showed considerable interindividual v ariability. Administration of temazepam led to a significant improveme nt in the objective parameters sleep period efficiency, wake time afte r sleep onset, and sleep efficiency and in the subjective assessment o f sleep quality. No significant correlations were observed between the pharmacokinetic-pharmacodynamic-derived parameters and the improvemen t in objective or subjective sleep parameters. Conclusion: In subjects with primary insomnia the administration of 20 mg oral temazepam resu lts in changes in both the pharmacodynamic measures and in quality of sleep. No individual correlations between the pharmacodynamic measures and quality of sleep were observed. We concluded that the investigate d pharmacodynamic measures are of value in the first assessment of cli nical efficacy and for the selection of the dose(s) to be investigated in subsequent trials that aim at showing clinical efficacy. However, the conclusive quantification of clinical efficacy should be performed only on the basis of the clinical end point itself.