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

Abstract 

Objectives: To measure GABA_A benzodiazepine receptor sensitivity in patients taking benzodiazepines and compare with matched controls. Methods: Seven patients who were on prescribed benzodiazepines for an anxiety disorder or insomnia were recruited from general practice and an adult mental health service outpatient clinic. They were matched with seven volunteers. All subjects received an intravenous injection of midazolam 50 µg/kg in 10 ml normal saline over 10 min. Objective responses to midazolam were assessed using saccadic eye movement velocity slowing and subjective assessments using visual analogue scales. Measurements were recorded for 120 min and plasma midazolam concentrations obtained at 15-min intervals post-infusion to 120 min. Ratios of pharmacodynamic/pharmacokinetic effects were obtained for each individual to estimate GABA_A benzodiazepine receptor sensitivity. Results: Patients had an attenuated response to midazolam on both subjective and objective measures. GABA_A benzodiazepine receptor sensitivity was significantly reduced in the patient group. Conclusions: Chronic treatment with benzodiazepines was associated with reduced effects of midazolam. Saccadic eye movement velocity was especially sensitive as a measure of attenuated response.