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


METHODS
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.


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


METHODS
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.


CONCLUSIONS
High dose diazepam significantly alters subjective drug responses and psychological performance in patients maintained on methadone and buprenorphine.
Lintzeris
Nicholas
N
National Addiction Centre, Institute of Psychiatry, Kings College London, and South London and Maudsley NHS Trust, P.O. Box 48, 4 Windsor Walk, Denmark Hill, London SE5 8AF, United Kingdom. nicholas.lintzeris@sswahs.nsw.gov.au
Mitchell
Timothy B
TB
Bond
Alyson J
AJ
Nestor
Liam
L
Strang
John
J
D000328:Adult; D002047:Buprenorphine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D003975:Diazepam / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006207:Half-Life; D006801:Humans; D008657:Metabolic Clearance Rate; D008691:Methadone / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D009293:Opioid-Related Disorders / Q000097:blood / Q000188:drug therapy*; D010100:Oxygen / Q000097:blood
D002047:Buprenorphine; D003975:Diazepam; D010100:Oxygen; D008691:Methadone