Assessment of GABA(A) benzodiazepine receptor (GBzR) sensitivity in patients on benzodiazepines

Objectives: To measure GABA(A) benzodiazepine receptor sensitivity in patie nts taking benzodiazepines and compare with matched controls. Methods: Seve n patients who were on prescribed benzodiazepines for an anxiety disorder o r insomnia were recruited from general practice and an adult mental health service outpatient clinic. They were matched with seven volunteers. All sub jects received an intravenous injection of midazolam 50 mu g/kg in 10 ml no rmal saline over 10 min. Objective responses to midazolam were assessed usi ng saccadic eye movement velocity slowing and subjective assessments using visual analogue scales. Measurements were recorded for 120 min and plasma m idazolam concentrations obtained at 15-min intervals post-infusion to 120 m in. Ratios of pharmacodynamic/pharmacokinetic effects were obtained for eac h individual to estimate GABA(A) benzodiazepine receptor sensitivity. Resul ts: Patients had an attenuated response to midazolam on both subjective and objective measures, GABA(A) benzodiazepine receptor sensitivity was signif icantly reduced in the patient group. Conclusions: Chronic treatment with b enzodiazepines was associated with reduced effects of midazolam. Saccadic e ve movement velocity was especially sensitive as a measure of attenuated re sponse.