Double-blind randomized trial of buprenorphine and methadone in opiate dependence

Abstract

This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure. Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and randomly assigned to substitution with buprenorphine or methadone. The retention rate was significantly better in the methadone maintained group (90 vs. 56%; P<0.001). Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine samples (buprenorphine 62%; methadone 59%) and positive urine specimens, as well as mean heroin craving scores decreased significantly over time (P=0.035 and P<0.001). The proportion of cocaine-positive toxicology results did not differ between groups. At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet, and 69.8 mg per day for methadone, respectively. Patient performance during maintenance was similar in both the groups. The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses. Thus, buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages.

Introduction

Although methadone maintenance is effective in reducing illicit heroin use, HIV infection rates, illegal behavior, as well as in improving other health and psychosocial conditions, some patients do not accept methadone treatment for fear of a future long-lasting withdrawal treatment and the need for daily dosing (Ball and Ross, 1991, Resnick et al., 1991). Buprenorphine, a partial -agonist (Martin et al., 1976) and -antagonist (Lewis, 1985) is one of the new pharmacological agents being currently investigated for the treatment of opiate dependence. Buprenorphine has some advantages over methadone; withdrawal symptoms after abrupt stopping are relatively mild compared with those of methadone (Jasinski et al., 1978, Bickel et al., 1988), and it has a long duration of action, which allows alternate-day dosing (Fudala et al., 1990, Amass et al., 1998). Previous clinical trials with buprenorphine have examined its efficacy using a fixed dosing procedure (Johnson et al., 1992, Kosten et al., 1993, Ling et al., 1996; Ling et al., 1998) and have compared a standard buprenorphine dose (8 mg per day) to a relatively low methadone dose in maintenance treatment (20–60 mg per day).

Johnson et al. (1992) have shown that a daily sublingual dose of 8 mg of buprenorphine was comparable with a 60 mg methadone dose concerning retention rates and opioid-negative urinalyses, whereas the study of Ling et al. (1996) revealed high-dose methadone to be superior over 8 mg of buprenorphine in long-term maintenance concerning retention, opioid use and opioid craving. Moreover, in an open study comparing methadone with buprenorphine tablets for heroin substitution Fischer et al. (1999) have found a better retention rate in the methadone maintained group but fewer illicit opiate consumption in the buprenorphine group (completers), using a flexible dosing procedure.

The present study differs by using ‘clinically guided’ dosages (Strain et al., 1994) with possible maxima of 16 mg of buprenorphine and 120 mg of methadone and by comparing the sublingual buprenorphine tablet, instead of the liquid buprenorphine formulation, to the standard liquid methadone. The aim of the study was, therefore, to evaluate the safety, effectiveness, and practicability of the buprenorphine tablet in the maintenance treatment of opioid dependent patients in three outpatient clinics. We hypothesized that buprenorphine would be as effective as the standard methadone maintenance treatment, or even better concerning the outcome measures retention in treatment and illicit opioid use.