Diazepam and methadone interactions in methadone maintenance

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Abstract
Survey study data and high diazepam use/abuse rates in methadone maintenance suggest that acute diazepam administration with daily methadone doses may enhance methadone effects. Acute subjective and physiologic effects of single oral doses of placebo, diazepam (20 and 40 mg), methadone (100, 150 and 200% of the maintenance dose) and 4 diazepam methadone dose combinations (20 and 40 mg diazepam with 100 and 150% of the maintenance dose) were assessed under double blind conditions. The subjects were 5 adult male patients on methadone maintenance with diazepam abuse histories who were receiving 50 to 60 mg methadone a day. Physiologic measures were continuously monitored for 30 min before and for 2 h after dosing. Pupil diameter and subjective responses were measured 15 min before dosing and 15, 30, 45, 60, 90 and 120 min after dosing. Methadone induced dose dependent increases in pupil constriction and scores on a subjective opioid effects rating scale, but diazepam had no significant effect on either. Methadone at 150% maintenance dose with 40 mg diazepam induced increases in these measures greater than those induced by either drug dose alone. Drug combinations, however, were more frequently identified as being benzodiazepine/barbiturate-like than as methadone-like. Although the subjective effcts of the drug combination are distinguishable from methadone alone, diazepam with methadone in methadone maintenance appears to increase some physiologic and subjective opioid efects that may be related to the relatively great diazepam use/abuse in this population.