Twenty-four anxious inpatients were treated with diazepam, amylobarbitone and placebo, each given in flexible dosage for one week, according to a fully-balanced design. Plasma concentrations of diazepam and of its metabolite nordiazepam and of amylobarbitone were determined after two, four and seven days of treatment. Clinical and psychological assessments were made after seven days of each treatment by means of psychiatrist rating scales, patient's self-rating and a comprehensive battery of performance measures. Diazepam and nordiazepam but not amylobarbitone were accumulating over the seven days of treatment. In patients on diazepam without previous amylobarbitone, nordiazepam accumulated more rapidly than diazepam over the week so that the ratio of diazepam to nordiazepam was 2.21 after two days but only 1.14 after seven days; those with previous amylobarbitone on the other hand always had nordiazepam concentrations higher than those of the administered drug and both were accumulating equally. Diazepam and nordiazepam were still detectable in most patients two weeks after the interruption of treatment. No correlations were found between drug concentrations and clinical and psychological effects.
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