Plasma Concentrations of Diazepam, Nordiazepam and Amylobarbitone after Short-term Treatment of Anxious Patients

Abstract

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.

A comparison of the clinical and psychological effects of diazepam and amylobarbitone in anxious patients.

“…The number of capsules ingested was carefully recorded each day and blood samples were taken during and at the end of each treatment for analysis for plasma concentrations. These results have been presented elsewhere (Tansella, Zimmermann Tansella, Ferrario, Preziati, Tognoni & Lader, 1978). During the trial no other psychotropic drugs were allowed, and no formal psychotherapy was given except of a simple supportive nature.…”

The Long-Term Treatment with Benzodiazepines: Suggestions for Further Research

“…As the most promising, specific, ad hoc measures of performance deficits to test in the laboratory, the card sorting and cancellation tasks, the Gibson Spiral Maze and tapping can be proposed despite their limitations in terms of their unknown relevance to real life performance (Zimmermann Tansella et al, 1978). These tests are economic and require only a few minutes of time, which is of particular importance when testing anxious patients.…”

Symposium Summary

“…There is evidence, by contrast, that the desmethylation of diazepam can be accelerated (Tansella et al, 1978).…”