TY - JOUR
T1 - Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients
AU - Lintzeris, N
AU - Mitchell, T B
AU - Bond, A J
AU - Nestor, L
AU - Strang, J
PY - 2007/12/1
Y1 - 2007/12/1
N2 - 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 (0 mg 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 SpO(2)), subjective (ARCI, VAS ratings) and performance (reaction time, cancellation task and Digit Symbol Substitution Test, DSST) measures were taken prior to and for 6 h 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 SpO(2) 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. (c) 2007 Elsevier Ireland Ltd. All rights reserved
AB - 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 (0 mg 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 SpO(2)), subjective (ARCI, VAS ratings) and performance (reaction time, cancellation task and Digit Symbol Substitution Test, DSST) measures were taken prior to and for 6 h 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 SpO(2) 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. (c) 2007 Elsevier Ireland Ltd. All rights reserved
U2 - 10.1016/j.drugalcdep.2007.05.019
DO - 10.1016/j.drugalcdep.2007.05.019
M3 - Article
SN - 1879-0046
VL - 91
SP - 187
EP - 194
JO - Drug and alcohol dependence
JF - Drug and alcohol dependence
IS - 2-3
ER -