Buprenorphine dosing every 1, 2, or 3 days in opioid-dependent patients

Warren K. Bickel, Leslie Amass, John P. Crean, Gary J. Badger

Administration of double the maintenance dose of buprenorphine has been shown to permit every-other-day dosing. Whether longer periods between dosing can be achieved is unknown. To examine whether triple the maintenance dose can be administered every 72 h without opioid withdrawal or intoxication. Sixteen opioid-dependent outpatients each received three conditions (1) the maintenance dose of buprenorphine every 24 h, (2) double the maintenance dose every 48 h, and (3) triple the maintenance dose every 72 h under double-blind placebo-controlled conditions. Each conditions was imposed in a random sequence for 21-22 days. Self report and observer measures were taken at 24-h intervals. No significant differences were observed on measures of opioid agonist and withdrawal effects between the dosing conditions. However, averaging effects across conditions may obscure important within-condition effects. When conditions were analyzed by individual days within a condition, several significant effects were observed. For example, 24 h after administration of triple the maintenance dose, significant effects were observed in eight opioid agonist measures. Also, 72 h after administration of triple the maintenance dose, significant effects were observed on four measures of withdrawal. Neither adverse medical reactions nor excessive opioid intoxication were observed. These results suggest that buprenorphine may be administered safely every 72 h by tripling the maintenance dose, with only minimal withdrawal complaints. Importantly, this 72-h dosing may permit patients to attend clinic thrice weekly without the use of take-home doses.