Assessment of Pharmacodynamics of a New “Controlled-Release” Form of Diazepam (Valium® CR Roche) by Quantitative EEG and Psychometric Analysis in Neurotic Subjects

Abstract

In a double-blind, double dummy, placebo-controlled study, the encephalotropic, psychotropic and pharmacodynamic properties of a new controlled-release form of diazepam (Valium CR) and the standard 5 mg tablets were compared by means of quantitative EEG and psychometric analysis methods. Ten patients exhibiting emotional and vegetative lability, nervousness and phobias, with an elevated neuroticism score (Eysenck), were recruited for the study. They were treated according to a crossover design with placebo, 15 mg diazepam CR and 3×5 mg diazepam with a 3-day wash-out interval between each administration period. They all received one tablet t.i.d. (8 a.m., 2 p.m. and 8 p.m.) and one capsule in the evening (8 p.m.). The main difference between the two forms of diazepam can be illustrated by the fact that in the morning, i.e. 8 hours after the evening medication, the increase in the anxiolytic drug effect on the CNS was consistently greater, to a statistically significant degree, during the Valium CR schedule than during the 5 mg tablet schedule. This was the case even after chronic administration of the drug over 5 days. The two forms of diazepam also differed with regard to their acute effects on attention, CFF and CNS activation. Attention deteriorated significantly less after the administration of the controlled-release forms than after 3 × 5 mg diazepam (3 hours after the morning medication). CFF was significantly more augmented in the morning after 5 mg diazepam than after 15 mg diazepam CR. There were no significant psychotropic inter-drug differences after chronic administration. The absence of clinically relevant changes in pulse rate, systolic and diastolic blood pressure and side-effects indicates extremely good tolerance of both forms of diazepam by neurotic patients.