Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal

TLDR

Nineteen heroin‑dependent men received escalating sublingual buprenorphine (2–8 mg daily) for 18 days, then were randomized to daily (8 mg) or alternate‑day dosing for 18 days, followed by 16 days of placebo. Alternate‑day buprenorphine produced greater opioid craving, dysphoria, and pupil dilation on placebo days, while abrupt cessation caused only mild‑to‑moderate withdrawal symptoms peaking at 3–5 days and lasting 8–10 days; daily dosing better controlled subtle withdrawal, yet a 48‑hour interval was tolerable. Clinical Pharmacology and Therapeutics 1990;47:525–534.

Abstract

Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52, all subjects received placebo. Subjects receiving buprenorphine on alternate days reported significantly greater urge for an opioid, increased dysphoria scores, and pupillary dilation on placebo days. After abrupt termination of buprenorphine, no withdrawal signs were detected with the Himmelsbach scale. However, subjects reported mild-to-moderate opioid withdrawal symptoms, peaking at 3 to 5 and lasting for 8 to 10 days. Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between-dose interval of 48 hours. Clinical Pharmacology and Therapeutics (1990) 47, 525–534; doi:10.1038/clpt.1990.67