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

Lintzeris, Nicholas; Mitchell, Timothy B.; Bond, Alyson J.; Nestor, Liam; Strang, John

doi:10.1016/j.drugalcdep.2007.05.019

« Previous Next »Drug and Alcohol Dependence
Volume 91, Issue 2 , Pages 187-194, 1 December 2007

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

Nicholas Lintzeris
- 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
- National Drug and Alcohol Research Centre, UNSW, Australia
- Corresponding author. Tel.: +61 431 585 515.
Timothy B. Mitchell
- 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
Alyson J. Bond
- 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
Liam Nestor
- Institute of Neuroscience, Trinity College, University of Dublin, Dublin, Ireland
John Strang
- 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

Received 26 May 2006; received in revised form 30 April 2007; accepted 24 May 2007.

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, 2×2 cross-over design in which the effects of diazepam dose (0mg versus 40mg) 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.

Keywords: Methadone, Buprenorphine, Benzodiazepines, Diazepam, Pharmacodynamic, Interactions