Examining the limits of the buprenorphine interdosing interval: daily, every-third-day and every-fifth-day dosing regimens

Addiction. 2001 Jun;96(6):823-34. doi: 10.1046/j.1360-0443.2001.9668234.x.


Aims: Opioid-dependent outpatients may be more likely to present for pharmacological treatment if less than daily dosing can be arranged. These studies compared opioid withdrawal symptoms during 24-, 72-, and 120-hour buprenorphine dosing regimens and evaluated participants' preferences for these different dosing regimens.

Participants: Thirty-three opioid-dependent participants received daily sublingual maintenance doses of 4 mg/70 kg (n = 14) or 8 mg/70 kg (n = 19) of liquid buprenorphine.

Methods: In Study I participants received, in a random order, three dosing regimens for five repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg), triple the daily maintenance dose every 72 hours (12 or 24 mg/70 kg) and quintuple the daily maintenance dose every 120 hours (20 or 40 mg/70 kg). Doses were administered under double-blind procedures, and placebos were administered on the interposed days during the latter two regimens. Subjective and observer ratings of opioid withdrawal symptoms were assessed daily prior to receipt of each dose. In Study II, a new group of participants received each of the three dosing regimens under open-dosing procedures and then chose between the different dosing regimens.

Findings: Opioid withdrawal symptoms increased significantly during the every-fifth-day dosing regimen in both the blind- and open-dosing studies. In the choice phase of Study II, only one participant (7%) chose quintuple-every-fifth-day dosing over all other dosing options.

Conclusions: These results suggest that the maximum duration of action of buprenorphine is less than 5 days when five times the daily maintenance dose is provided.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Appointments and Schedules
  • Buprenorphine / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Narcotics / administration & dosage*
  • Opioid-Related Disorders / drug therapy*
  • Patient Compliance
  • Patient Satisfaction
  • Substance Withdrawal Syndrome / drug therapy
  • Treatment Outcome


  • Narcotics
  • Buprenorphine