Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients

Abstract

Background: Benzodiazepine abuse is common among methadone- and buprenorphine-maintained patients; however interactions between these drugs under high dose conditions have not been adequately examined under controlled conditions.

Objective: To investigate the effects of co-administering diazepam with methadone or buprenorphine under high dose conditions.

Design: Double-blind, randomly ordered, 2 x 2 cross-over design in which the effects of diazepam dose (0mg versus 40 mg) and opioid dose (100% versus 150% normal dose) were examined over four sessions in methadone- and buprenorphine-maintained patients.

Participants: Four methadone- and seven buprenorphine-prescribed patients without concurrent dependence on other substances or significant medical co-morbidity.

Measures: Physiological (pulse rate, blood pressure, pupil size, respiratory rate and peripheral SpO2), subjective (ARCI, VAS ratings) and performance (reaction time, cancellation task and Digit Symbol Substitution Test, DSST) measures were taken prior to and for 6h post-dosing.

Results: High dose diazepam was associated with time-dependent increases in the intensity of subjective drug effects (strength of drug effect, sedation) and decreases in psychological performance (reaction time, DSST) for both methadone and buprenorphine patients. These effects were generally independent of the opioid dose administered. High dose opioid administration (150% normal dose) was associated with reductions in overall SpO2 levels and performance (reaction time, DSST) in the methadone patients, but had virtually no impact on pharmacodynamic responses in the buprenorphine group.

Conclusion: High dose diazepam significantly alters subjective drug responses and psychological performance in patients maintained on methadone and buprenorphine.