Titre du document / Document title

Flumazenil-precipitated withdrawal in healthy volunteers following repeated diazepam exposure

Auteur(s) / Author(s)

MINTZER Miriam Z. ⁽¹⁾ ; GRIFFITHS Roland R. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, ETATS-UNIS

Résumé / Abstract

Rationale: Parametric preclinical studies of the benzodiazepine antagonist flumazenil have contributed to the understanding of the physical dependence associated with chronic benzodiazepine use. However, few parametric studies have been conducted in human participants. Objective: This study was designed to assess the effect of duration of benzodiazepine exposure on the intensity of flumazenil-precipitated withdrawal in healthy volunteers. Method: Participants were randomly assigned to receive either oral diazepam (15 mg/70 kg; n=10) or placebo (n=8) capsules nightly for 28 days. Effects of flumazenil (1 mg/70 kg, intravenously administered) were assessed in challenge sessions conducted before capsule ingestion, and after 1, 7, 14, and 28 days of capsule ingestion. Results: Flumazenil produced a profile of participant-rated effects consistent with benzodiazepine withdrawal that peaked immediately after completion of the 5-min flumazenil injection and rapidly dissipated thereafter. The magnitude of these effects was comparable after 7, 14, and 28 days of diazepam. Flumazenil also produced modest elevations in blood pressure and decreases in skin temperature in the diazepam group, both of which were sustained throughout the approximate 60-min session. Conclusions: These findings support previous human research studies indicating that flumazenil precipitates withdrawal after short chronic exposure to benzodiazepines and suggests that duration of exposure does not influence the intensity of withdrawal beyond the first week of exposure.

Revue / Journal Title

Psychopharmacologia   ISSN 0033-3158   CODEN PSYPAG 

Source / Source

2005, vol. 178, n^o2-3, pp. 259-267 [9 page(s) (article)] (44 ref.)

Langue / Language

Anglais

Editeur / Publisher

Springer, Berlin, ALLEMAGNE  (1959) (Revue)

Mots-clés anglais / English Keywords

Benzodiazepine derivatives ; Benzodiazepine receptor ; Benzodiazepine antagonist ; Hypnotic ; Anticonvulsant ; Psychotropic ; Dependence ; Tranquillizer ; Diazepam ; Multiple dose ; Human ; Healthy subject ; Disintoxication ; Poison withdrawal ; Flumazenil ;

Mots-clés français / French Keywords

Benzodiazépine dérivé ; Récepteur benzodiazépinique ; Antagoniste benzodiazépine ; Hypnotique ; Anticonvulsivant ; Psychotrope ; Dépendance ; Tranquillisant ; Diazépam ; Dose répétée ; Homme ; Individu sain ; Désintoxication ; Sevrage toxique ; Flumazénil ;

Mots-clés espagnols / Spanish Keywords

Benzodiazepina derivado ; Receptor benzodiazepínico ; Antagonista benzodiazepina ; Hipnótico ; Anticonvulsivante ; Psicotropo ; Dependencia ; Tranquilizante ; Diazepam ; Dosis múltiple ; Hombre ; Individuo sano ; Desintoxicación ; Destete tóxico ; Flumazenilo ;

Localisation / Location

INIST-CNRS, Cote INIST : 1761, 35400012627320.0180