Treatment of Opiate Addiction with Sublingual Buprenorfine and Naloxone

A follow-up study 2 randomized 1080 opioid-dependent participants entering seven opioid treatment programs in the United States to receive open-label buprenorphine/naloxone or methadone for up to 24 weeks; 795 participants completed in-person interviews (~74% follow-up interview rate) covering on average 4.5 years. Mortality was not different between the two randomized conditions, with 23 (3.6%) of 630 participants randomized to buprenorphine having died versus 26 (5.8%) of 450 participants randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone [42.8 versus 31.7% positive opioid urine specimens, P < 0.01, effect size (h) = 0.23 (0.09 to 0.38); 5.8 days versus 4.4 days of past 30-day heroin use, P < 0.05, effect size (d) = 0.14 (0.00, 0.28)]. Opioid use during the follow-up period by randomization condition was also significant (F(7,39,600) = 3.16; P < 0.001) due mainly to less treatment participation among participants randomized to buprenorphine than methadone. Less opioid use was associated with both buprenorphine and methadone treatment (relative to no treatment); no difference was found between the two treatments. Individuals who are white or used cocaine at baseline responded better to methadone than to buprenorphine.

In a multicentre trial 1 326 opiate-addicted persons were randomized to office-based treatment with either sublingual tablets consisting of buprenorfine 16 mg and naloxone 4 mg, buprenorfine alone 16 mg, or placebo. The proportions of urine samples negative for opiates were greater in the combined-treatment and buprenorfine groups (17.8 and 20.7 percent) than in the placebo group (5.8 percent), p<0.001 for both comparisons. Rates of adverse events were similar in the active-treatment and placebo groups. Results of an open-label follow-up study indicated that combined treatment was safe and well tolerated.

Comment: The quality of evidence is downgraded by study limitations (open-label study).

Comment: The inclusion of naloxone in the sublingual tablet is not intended to increase the efficacy of treatment but to prevent misuse of buprenorfine by the parenteral route - the combination precipitates withdrawals symptoms when administered intravenously to opiate-dependent persons.

References

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• Hser YI, Evans E, Huang D et al. Long-term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi-site trial. Addiction 2016;111(4):695-705. [PubMed]