, Volume 69, Issue 5, pp 577–607 | Cite as


A Review of its Use in the Treatment of Opioid Dependence
  • Jennifer S. Orman
  • Gillian M. KeatingEmail author
Adis Drug Evaluation



Buprenorphine/naloxone (Suboxone®) comprises the partial μ-opioid receptor agonist buprenorphine in combination with the opioid antagonist naloxone in a 4: 1 ratio. When buprenorphine/naloxone is taken sublingually as prescribed, the naloxone exerts no clinically significant effect, leaving the opioid agonist effects of buprenorphine to predominate. However, when buprenorphine/naloxone is parenterally administered in patients physically dependent on full agonist opioids, the opioid antagonism of naloxone causes withdrawal effects, thus reducing the abuse potential of the drug combination.

Buprenorphine/naloxone is an effective maintenance therapy for opioid dependence and has generally similar efficacy to methadone, although more data are needed. Less frequent dispensing of buprenorphine/naloxone (e.g. thrice weekly) does not appear to compromise efficacy and can improve patient satisfaction. Buprenorphine/naloxone is more effective than clonidine as a medically-supervised withdrawal therapy. Moreover, buprenorphine/naloxone is a generally well tolerated medically-supervised withdrawal and maintenance treatment. Thus, sublingual buprenorphine/naloxone is a valuable pharmacotherapy for the treatment of opioid dependence.

Pharmacological Properties

Buprenorphine is a partial agonist at the μ-opioid receptor and an antagonist at the κ-opioid receptor. It has high binding affinity at both receptors and competes with other agonists, such as methadone, heroin (diamorphine) and morphine, at the m-opioid receptor. Opioid agonist effects of buprenorphine are less than the maximal effects of full opioid agonists, such as morphine, and are limited by a ‘ceiling’ effect. The drug may produce a lower degree of physical dependence than full opioid agonists (e.g. heroin, morphine or methadone).

Naloxone is an opioid antagonist without agonist properties. In the absence of opioid agonism by other drugs it exhibits no pharmacodynamic activity when administered in recommended doses. When opioids are present, naloxone prevents or reverses their effects. Limited sublingual absorption and almost complete first-pass metabolism restrict the effects of naloxone when it is administered sublingually in recommended doses.

Following sublingual administration in an opioid-dependent population, buprenorphine/naloxone administered in a 4: 1 ratio has similar physiological and subjective effects to buprenorphine alone at equivalent buprenorphine doses. However, when administered parenterally to individuals dependent on full opioid agonists, this dose ratio increased opioid antagonist effects relative to buprenorphine alone.

Therapeutic Efficacy

In a 52-week pivotal trial of buprenorphine/naloxone maintenance therapy for opioid dependence, both buprenorphine/naloxone and buprenorphine alone increased the percentage of opioid-negative urine samples and decreased patients’ self-reported craving for opioids compared with placebo during a 4-week, double-blind treatment period.

In addition, a 17-week, randomized, single-centre trial comparing maintenance therapy with buprenorphine/naloxone and methadone indicated no significant between-treatment difference in the percentage of opioid-negative urine samples. A 6-month, randomized, multicentre, maintenance therapy trial in opioid-dependent patients also demonstrated that buprenorphine/naloxone-based stepped care (with transition to methadone as necessary) was noninferior to methadone in terms of retention in treatment.

A 24-week, randomized, parallel-group trial, a 13-week, randomized trial of observed versus unobserved administration of buprenorphine/naloxone, and two 3-week, randomized, crossover studies also assessed the efficacy of buprenorphine/naloxone maintenance therapy with different counselling and/or medication-dispensing regimens. There were no significant differences in the reduction of illicit opioid use across study arms. However, patients appeared to prefer administration schedules in which they were less frequently required to attend a clinic or office for medication dispensing; unobserved, compared with observed, administration did not compromise treatment efficacy.

The proportion of patients both completing treatment and providing an opioid-free urine sample at treatment end was higher in patients receiving tapering doses of buprenorphine/naloxone than clonidine during medically-supervised 13-day withdrawal therapy in two randomized, open-label, multicentre studies, one in inpatients and one in outpatients.

A longer tapering schedule (28 vs 7 days) did not improve outcome in opioid-dependent patients in a randomized, open-label, multicentre, outpatient study. Significantly more patients receiving the 7- than the 28-day tapering schedule had a opioid-negative urine test at the end of the taper period, with no significant between-group differences at 1 or 3 months post-taper.

A 12-week tapering schedule of buprenorphine/naloxone was associated with better short-term treatment outcomes than a 14-day medically-supervised withdrawal regimen in adolescents and young adults aged 15–21 years enrolled in a randomized, open-label, multicentre, outpatient study. Longer term, there were no significant differences between the regimens in terms of self-reported opioid use or injecting.


Four weeks’ therapy with buprenorphine/naloxone was generally well tolerated in the pivotal, 52-week trial of buprenorphine/naloxone as a maintenance therapy for opioid dependence, and differences in the overall rate of adverse events were not significant between treatment groups. Across treatment groups, the most commonly reported adverse events were headache, withdrawal syndrome, pain, nausea and insomnia. Of these adverse events, only the occurrence of withdrawal syndrome was significantly different across treatment groups, and this occurred with greater frequency in the placebo group than the buprenorphine/naloxone and buprenorphine alone groups. In the ≈48-week, open-label assessment of safety included in this trial, treatment-related adverse events that occurred in >10% of patients were insomnia, constipation, nausea, sweating, withdrawal syndrome and headache.

Limited tolerability data are available versus active comparators other than buprenorphine alone. Versus clonidine in medically-supervised withdrawal treatment, the number of adverse events reported per patient per day was significantly fewer with buprenorphine/naloxone than clonidine in both the inpatient and outpatient settings.


Clonidine Naloxone Heroin Buprenorphine Opioid Dependence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Wolters Kluwer Health ¦ AdisMairangi Bay, North Shore, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthPhiladelphiaUSA

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