Controlled opioid withdrawal evaluation during 72 h dose omission in buprenorphine-maintained patients

Buprenorphine's clinical utility as an opioid dependence pharmacotherapy may be enhanced with less-than-daily dosing. This study assessed opioid withdrawal after an acute 72 h dose omission in buprenorphine-maintained patients (8 mg/day s.l.). Eight outpatients required to remain free of opioids, cocaine and benzodiazepines completed four double-blind, double-dummy, Latin-square ordered conditions. Test conditions of 8 or 16 mg s.l. buprenorphine were followed by 2 days of placebo dosing. Control conditions were buprenorphine maintenance (8 mg/day), to provide a reference for evaluation of placebo test days and naloxone administration (10 mg/70 kg i.m.) during 8 mg buprenorphine maintenance to assess withdrawal measure sensitivity. Subjective measures and pupil diameter were significantly influenced only by naloxone. The lack of subjective symptoms and physiological signs of opioid withdrawal during 72 h of acute dose omission supports the feasibility of less-than-daily dosing at buprenorphine doses of 8 mg/day in patients who have demonstrated an ability to remain drug-free for an extended period.