Evaluation of an injection depot formulation of buprenorphine: placebo comparison


George E. Bigelow 5510 Nathan Shock Drive Baltimore MD 21224 USA Tel: 410-550-0035 Fax: 410-550-0030 E-mail: bigelow@jhmi.edu


Aims  Buprenorphine is a mu-opioid partial agonist that is marketed in a sublingual formulation as a treatment for opioid dependence. A microcapsule depot sustained-release formulation has been developed which may offer effective treatment  of  opioid  dependence  while  also  minimizing  risks  of  illicit  diversion or patient non-compliance. The present study examined the efficacy of depot buprenorphine in suppressing the opioid withdrawal syndrome and in attenuating the effects of exogenous opioid challenge.

Design  A placebo-controlled, double-blind, randomized trial.

Setting  A closed residential research facility.

Participants  A total of 15 opioid-dependent participants were enrolled into the 6-week study.

Intervention  Fifteen participants were randomized to receive a single subcutaneous depot injection containing buprenorphine (58 mg) or placebo. Two participants, both of whom received placebo, terminated participation after depot administration. Thirteen participants (six buprenorphine, seven placebo) completed the 6-week study and were assessed throughout the study for signs and symptoms of opioid withdrawal and for response to weekly subcutaneous challenges with 3 mg hydromorphone.

Measurement  Subjective, physiological and observer-rated indices of opioid withdrawal and opioid agonist effects.

Findings  Depot buprenorphine provided more effective relief from opioid withdrawal than placebo, as evidenced by significantly fewer buprenorphine participants requiring supplemental medications for withdrawal suppression after depot administration compared to participants receiving placebo. In the weekly hydromorphone challenge sessions, depot buprenorphine significantly reduced opioid response on measures of subjective effects and pupillary diameter.

Conclusions  Results from this double-blind, placebo-controlled study indicate that depot buprenorphine is effective in providing both withdrawal suppression and opioid blockade. Future studies examining additional doses and repeated dosing regimens with depot buprenorphine are warranted.