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Evidence summaries

Treatment of Opiate Addiction with Sublingual Buprenorfine and Naloxone

A sublingual combination tablet of buprenorfine and naloxone appears to be effective for opiate addiction. Level of evidence: "B"

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

    • Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, Collins J, Raisch D, Casadonte P, Goldsmith RJ, Ling W, Malkerneker U, McNicholas L, Renner J, Stine S, Tusel D, Buprenorphine/Naloxone Collaborative Study Group. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med 2003 Sep 4;349(10):949-58. [PubMed]
    • 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]

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