Advertisement

Drugs

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

Buprenorphine/Naloxone

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

Summary

Abstract

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.

Tolerability

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.

Keywords

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.

References

  1. 1.
    US Department of Health and Human Services. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction: a treament improvement protocol TIP 40 [online]. Available from URL: http://www.naabt.org/links/TIP_40_PDF.pdf [Accessed 2007 Mar 1]
  2. 2.
    Best SE, Oliveto AH, Kosten TR. Opioid addiction: recent advances in detoxification and maintenance therapy. CNS Drugs 1996 Oct; 6(4): 301–14CrossRefGoogle Scholar
  3. 3.
    National Institute on Drug Abuse. Principles of drug addiction treatment: a research-based guide [online]. Available from URL: http://www.drugabuse.gov/PODAT/PODATIndex.html [Accessed 2007 Jun 18]
  4. 4.
    Srivastava A, Kahan M. Buprenorphine: a potential new treatment option for opioid dependence. CMAJ 2006 Jun 20; 174(13): 1835–6PubMedCrossRefGoogle Scholar
  5. 5.
    McCance-Katz EF. Office-based buprenorphine treatment for opioid-dependent patients. Harv Rev Psychiatry 2004 Nov/Dec; 12(6): 321–38PubMedCrossRefGoogle Scholar
  6. 6.
    Mattick RP, Kimber J, Breen C, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2003 Apr 22; (2): CD002207Google Scholar
  7. 7.
    Goldman FR, Thistel CI. Diversion of methadone: illicit methadone use among applicants to two metropolitan drug abuse programs. Int J Addict 1978 Aug; 13(6): 855–62PubMedGoogle Scholar
  8. 8.
    Sullivan LE, Chawarski M, O’Connor PG, et al. The practice of office-based buprenorphine treatment of opioid dependence: is it associated with new patients entering into treatment? Drug Alcohol Depend 2005 Jul; 79(1): 113–6PubMedCrossRefGoogle Scholar
  9. 9.
    Alho H, Sinclair D, Vuori E, et al. Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Drug Alcohol Depend 2007 Apr 17; 88(1): 75–8PubMedCrossRefGoogle Scholar
  10. 10.
    Chapleo CB, Walter DS. The buprenorphine-naloxone combination product. Res Clin Forums 1997; 19(2): 55–8Google Scholar
  11. 11.
    European Medicines Agency. Scientific discussion (Suboxone) [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/suboxone/069706en6.pdf [Accessed 2007 Jan 4]
  12. 12.
    Mégarbane B, Hreiche R, Pirnay S, et al. Does high-dose buprenorphine cause respiratory depression? Possible mechanisms and therapeutic consequences. Toxicol Rev 2006; 25(2): 79–85PubMedCrossRefGoogle Scholar
  13. 13.
    Jasinski DR, Pevnick JS, Griffith JD. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch Gen Psychiatry 1978 Apr; 35(4): 501–16PubMedCrossRefGoogle Scholar
  14. 14.
    Wesson DR. Buprenorphine in the treatment of opiate dependence: its pharmacology and social context of use in the U.S. J Psychoactive Drugs 2004 May; Suppl. 2: 119–28PubMedCrossRefGoogle Scholar
  15. 15.
    Walsh SL, Preston KL, Stitzer ML, et al. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther 1994 May; 55(5): 569–80PubMedCrossRefGoogle Scholar
  16. 16.
    Ciraulo DA, Hitzemann RJ, Somoza E, et al. Pharmacokinetics and pharmacodynamics of multiple sublingual buprenorphine tablets in dose-escalation trials. J Clin Pharmacol 2006; 46: 179–92PubMedCrossRefGoogle Scholar
  17. 17.
    Greenwald MK, Johanson C-E, Moody DE, et al. Effects of buprenorphine maintenance dose on μ-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacology 2003 Nov; 28(11): 2000–9PubMedCrossRefGoogle Scholar
  18. 18.
    Zubieta J-K, Greenwald MK, Lombardi U, et al. Buprenorphine-induced changes in mu-opioid receptor availability in male heroin-dependent volunteers: a preliminary study. Neuropsychopharmacology 2000; 23(3): 326–34PubMedCrossRefGoogle Scholar
  19. 19.
    Umbricht A, Huestis MA, Cone EJ, et al. Effects of high-dose intravenous buprenorphine in experienced opioid abusers. J Clin Psychopharmacol 2004 Oct; 24(5): 479–87PubMedCrossRefGoogle Scholar
  20. 20.
    Bickel WK, Stitzer ML, Bigelow GE, et al. Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans. J Pharmacol Exp Ther 1988 Oct; 247(1): 47–53PubMedGoogle Scholar
  21. 21.
    Lintzeris N, Mitchell TB, Bond A, et al. Interactions on mixing diazepam with methadone or buprenorphine in maintenance patients. J Clin Psychopharmacol 2006 Jun; 26(3): 274–83PubMedCrossRefGoogle Scholar
  22. 22.
    Walsh SL, June HL, Schuh KJ, et al. Effects of buprenorphine and methadone in methadone-maintained subjects. Psychopharmacology (Berl) 1995; 119(3): 268–76CrossRefGoogle Scholar
  23. 23.
    European Medicines Agency. Suboxone: summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/suboxone/H-697-PI-en.pdf [Accessed 2009 Feb 11]
  24. 24.
    Eissenberg T, Greenwald MK, Johnson RE, et al. Buprenorphine’s physical dependence potential: antagonist-precipitated withdrawal in humans. J Pharmacol Exp Ther 1996; 276(2): 449–59PubMedGoogle Scholar
  25. 25.
    Bliesener N, Albrecht S, Schwager A, et al. Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence. J Clin Endocrinol Metab 2005 Jan; 90(1): 203–6PubMedCrossRefGoogle Scholar
  26. 26.
    Hallinan R, Byrne A, Agho K, et al. Erectile dysfunction in men receiving methadone and buprenorphine maintenance treatment. J Sex Med 2008 Mar; 5(3): 684–92PubMedCrossRefGoogle Scholar
  27. 27.
    Soyka M, Lieb M, Kagerer S, et al. Cognitive functioning during methadone and buprenorphine treatment: results of a randomized clinical trial. J Clin Psychopharmacol 2008 Dec; 28(6): 699–703PubMedCrossRefGoogle Scholar
  28. 28.
    Wedam EF, Bigelow GE, Johnson RE, et al. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med 2007 Dec 10/24; 167(22): 2469–75PubMedCrossRefGoogle Scholar
  29. 29.
    Fanoe S, Hvidt C, Ege P, et al. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen. Heart 2007 Sep; 93(9): 1051–5PubMedCrossRefGoogle Scholar
  30. 30.
    Endo Laboratories. Narcan® (naloxone hydrochloride injection) label [online]. Available from URL: http://www.fda.gov [Accessed 2007 Jan 30]
  31. 31.
    Loimer N, Hofmann P, Chaudry HR. Nasal administration of naloxone is as effective as the intravenous route in opiate addicts. Int J Addict 1994; 29(6): 819–27PubMedGoogle Scholar
  32. 32.
    Johnson RE, Strain EC, Amass L. Buprenorphine: how to use it right. Drug Alcohol Depend 2003; 70: S59–77PubMedCrossRefGoogle Scholar
  33. 33.
    Robinson GM, Dukes PD, Robinson BJ, et al. The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Drug Alcohol Depend 1993 Jun; 33(1): 81–6PubMedCrossRefGoogle Scholar
  34. 34.
    Robinson SE. Buprenorphine-containing treatments: place in the management of opioid addiction. CNS Drugs 2006; 20(9): 697–712PubMedCrossRefGoogle Scholar
  35. 35.
    Fudala PJ, Yu E, Macfadden W, et al. Effects of buprenorphine and naloxone in morphine-stabilized opioid addicts. Drug Alcohol Depend 1998 Mar 1; 50: 1–8PubMedCrossRefGoogle Scholar
  36. 36.
    Mendelson J, Jones RT, Fernandez I, et al. Buprenorphine and naloxone interactions in opiate-dependent volunteers. Clin Pharmacol Ther 1996 Jul; 60(1): 105–14PubMedCrossRefGoogle Scholar
  37. 37.
    Bigelow GE, Preston KL, Liebson IA. Abuse liability assessment of buprenorphine-naloxone combinations. NIDA Res Monogr 1987; 76: 145–9PubMedGoogle Scholar
  38. 38.
    Mendelson J, Jones RT, Welm S, et al. Buprenorphine and naloxone interactions in methadone maintenance patients. Biol Psychiatry 1997 Jun 1; 41(11): 1095–101PubMedCrossRefGoogle Scholar
  39. 39.
    Mendelson J, Jones RT, Welm S, et al. Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers. Psychopharmacology (Berl) 1999 Jan; 141(1): 37–46CrossRefGoogle Scholar
  40. 40.
    Harris DS, Jones RT, Welm S, et al. Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine. Drug Alcohol Depend 2000 Dec 22; 61(1): 85–94PubMedCrossRefGoogle Scholar
  41. 41.
    Preston KL, Bigelow GE, Liebson IA. Buprenorphine and naloxone alone and in combination in opioid-dependent humans. Psychopharmacology (Berl) 1988; 94(4): 484–90CrossRefGoogle Scholar
  42. 42.
    Stoller KB, Bigelow GE, Walsh SL, et al. Effects of buprenorphine/naloxone in opioid-dependent humans. Psychopharmacology (Berl) 2001 Mar; 154(3): 230–42CrossRefGoogle Scholar
  43. 43.
    Reckitt Benckiser Pharmaceuticals, Inc. Suboxone (buprenorphine HCl and naloxone HCl dihydrate sublingual tablets)/Subutex (buprenorphine HCl sublingual tablets): US prescribing information [online]. Available from URL: http://www.suboxone.com/patients/pi/ [Accessed 2009 Feb 11]
  44. 44.
    Strain EC, Walsh SL, Bigelow GE. Blockade of hydromor-phone effects by buprenorphine/naloxone and buprenorphine. Psychopharmacology (Berl) 2002 Jan 1; 159(2): 161–6CrossRefGoogle Scholar
  45. 45.
    Comer SD, Walker EA, Collins ED. Buprenorphine/naloxone reduces the reinforcing and subjective effects of heroin in heroin-dependent volunteers. Psychopharmacology (Berl) 2005 Oct; 181(4): 664–75CrossRefGoogle Scholar
  46. 46.
    Correia CJ, Walsh SL, Bigelow GE, et al. Effects associated with double-blind omission of buprenorphine/naloxone over a 98-h period. Psychopharmacology (Berl) 2006 Sep 30; 189(3): 297–306CrossRefGoogle Scholar
  47. 47.
    Rosado J, Walsh SL, Bigelow GE, et al. Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained on 100 mg of daily methadone. Drug Alcohol Depend 2007 Oct 8; 90(2): 261–9PubMedCrossRefGoogle Scholar
  48. 48.
    Weinhold LL, Preston KL, Farre M, et al. Buprenorphine alone and in combination with naloxone in non-dependent humans. Drug Alcohol Depend 1992 Aug; 30(3): 263–74PubMedCrossRefGoogle Scholar
  49. 49.
    Mintzer MZ, Correia CJ, Strain EC. A dose-effect study of repeated administration of buprenorphine/naloxone on performance in opioid-dependent volunteers. Drug Alcohol Depend 2004 May 10; 74(2): 205–9PubMedCrossRefGoogle Scholar
  50. 50.
    Rapeli P, Fabritius C, Alho H, et al. Methadone vs. buprenorphine/naloxone during early opioid substitution treatment: a naturalistic comparison of cognitive performance relative to healthy controls. BMC Clin Pharmacol 2007 Jun 12; 7: 5PubMedCrossRefGoogle Scholar
  51. 51.
    Baker JR, Best AM, Pade PA, et al. Effect of buprenorphine and antiretroviral agents on the QT interval in opioid-dependent patients. Ann Pharmacother 2006 Mar; 40(3): 392–6PubMedCrossRefGoogle Scholar
  52. 52.
    Chiang CN, Hawks RL. Pharmacokinetics of the combination tablet of buprenorphine and naloxone. Drug Alcohol Depend 2003 May 21; 70 Suppl. 2: S39–47PubMedCrossRefGoogle Scholar
  53. 53.
    Elkader A, Sproule B. Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet 2005; 44(7): 661–80PubMedCrossRefGoogle Scholar
  54. 54.
    Compton P, Ling W, Chiang N, et al. Pharmacokinetics of buprenorphine: a comparison of sublingual tablet versus liquid after chronic dosing. J Addict Med 2007 Jun; 1(2): 88–95PubMedCrossRefGoogle Scholar
  55. 55.
    Center for Drug Evaluation and Research. Clinical pharmacology and biopharmaceutics reviews: application number: 20-732, 20-733 (Suboxone®) [online]. Available from URL: http://www.fda.gov/cder/foi/nda/2002/20-733_Subutex_BioPharmr.pdf [Accessed 2007 Feb 8]
  56. 56.
    Harris DS, Mendelson JE, Lin ET, et al. Pharmacokinetics and subjective effects of sublingual buprenorphine, alone or in combination with naloxone: lack of dose proportionality. Clin Pharmacokinet 2004; 43(5): 329–40PubMedCrossRefGoogle Scholar
  57. 57.
    Pérez de los Cobos J, Martin S, Etcheberrigaray A, et al. A controlled trial of daily versus thrice-weekly buprenorphine administration for the treatment of opioid dependence. Drug Alcohol Depend 2000 Jun 1; 59(3): 223–33CrossRefGoogle Scholar
  58. 58.
    McCance-Katz EF, Moody DE, Morse GD, et al. Interactions between buprenorphine and antiretrovirals: I. The nonnucleoside reverse-transcriptase inhibitors efavirenz and delavirdine. Clin Infect Dis 2006 Dec 15; 43 Suppl. 4: S224–34PubMedCrossRefGoogle Scholar
  59. 59.
    McCance-Katz EF, Moody DE, Smith PF, et al. Interactions between buprenorphine and antiretrovirals: II. The protease inhibitors nelfinavir, lopinavir/ritonavir, and ritonavir. Clin Infect Dis 2006 Dec 15; 43 Suppl. 4: S235–46PubMedCrossRefGoogle Scholar
  60. 60.
    McCance-Katz EF, Moody DE, Morse GD, et al. Interaction between buprenorphine and atazanavir or atazanavir/ritonavir. Drug Alcohol Depend 2007 Dec 1; 91(2–3): 269–78PubMedCrossRefGoogle Scholar
  61. 61.
    Strain EC, Stitzer ML, Liebson IA, et al. Comparison of buprenorphine and methadone in the treatment of opioid dependence. Am J Psychiatry 1994 Jul; 151(7): 1025–30PubMedGoogle Scholar
  62. 62.
    Johnson RE, Jaffe JH, Fudala PJ. A controlled trial of buprenorphine treatment for opioid dependence. JAMA 1992 May 27; 267(20): 2750–5PubMedCrossRefGoogle Scholar
  63. 63.
    Johnson RE, Chutuape MA, Strain EC, et al. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med 2000 Nov 2; 343(18): 1290–7PubMedCrossRefGoogle Scholar
  64. 64.
    Johnson RE, Eissenberg T, Stitzer ML, et al. A placebo controlled trial of buprenorphine as a treatment for opioid dependence. Drug Alcohol Depend 1995; 40(1): 17–25PubMedCrossRefGoogle Scholar
  65. 65.
    Vigezzi P, Guglielmino L, Marzorati P, et al. Multimodal drug addiction treatment: a field comparison of methadone and buprenorphine among heroin- and cocaine-dependent patients. J Subst Abuse Treat 2006; 31(3): 3–7PubMedCrossRefGoogle Scholar
  66. 66.
    Mattick RP, Ali R, White JM, et al. Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients. Addiction 2003; 98(4): 441–52PubMedCrossRefGoogle Scholar
  67. 67.
    Ling W, Charuvastra C, Collins JF, et al. Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial. Addiction 1998; 93(4): 475–86PubMedCrossRefGoogle Scholar
  68. 68.
    Schottenfeld RS, Chawarski MC, Mazlan M. Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial. Lancet 2008 Jun 28; 371(9631): 2192–200PubMedCrossRefGoogle Scholar
  69. 69.
    Cheskin LJ, Fudala PJ, Johnson RE. A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids. Drug Alcohol Depend 1994; 36(2): 115–21PubMedCrossRefGoogle Scholar
  70. 70.
    O’Connor PG, Carroll KM, Shi JM, et al. Three methods of opioid detoxification in a primary care setting: a randomized trial. Ann Intern Med 1997 Oct 1; 127(7): 526–30PubMedGoogle Scholar
  71. 71.
    Seifert J, Metzner C, Paetzold W, et al. Detoxification of opiate addicts with multiple drug abuse: a comparison of buprenorphine vs. methadone. Pharmacopsychiatry 2002; 35(5): 159–64PubMedCrossRefGoogle Scholar
  72. 72.
    Janiri L, Mannelli P, Persico AM, et al. Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine. Drug Alcohol Depend 1994; 36(2): 139–45PubMedCrossRefGoogle Scholar
  73. 73.
    Bell J, Byron G, Gibson A, et al. A pilot study of buprenorphine-naloxone combination tablet (Suboxone®) in treatment of opioid dependence. Drug Alcohol Rev 2004 Sep; 23(3): 311–7PubMedCrossRefGoogle Scholar
  74. 74.
    Fudala PJ, Bridge TP, Herbert S, et al. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med 2003 Sep 4; 349(10): 949–58PubMedCrossRefGoogle Scholar
  75. 75.
    Kamien JB, Branstetter SA, Amass LA. Buprenorphine-nalox-one versus methadone maintenance therapy: a randomised double-blind trial with opioid dependent patients. Heroin Addict Relat Clin Probl 2008; 10(4): 5–18Google Scholar
  76. 76.
    Kakko J, Grönbladh L, Svanborg KD, et al. A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial. Am J Psychiatry 2007 May; 164(5): 797–803PubMedCrossRefGoogle Scholar
  77. 77.
    Fiellin DA, Pantalon MV, Chawarski MC, et al. Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. N Engl J Med 2006 Jul 27; 355(4): 365–74PubMedCrossRefGoogle Scholar
  78. 78.
    Amass L, Kamien JB, Mikulich SK. Thrice-weekly supervised dosing with the combination buprenorphine-naloxone tablet is preferred to daily supervised dosing by opioid-dependent humans. Drug Alcohol Depend 2001 Jan 1; 61(2): 173–81PubMedCrossRefGoogle Scholar
  79. 79.
    Amass L, Kamien JB, Mikulich SK. Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine-naloxone tablet. Drug Alcohol Depend 2000 Feb 1; 58(1–2): 143–52PubMedCrossRefGoogle Scholar
  80. 80.
    Bell J, Shanahan M, Mutch C, et al. A randomized trial of effectiveness and cost-effectiveness of observed versus unobserved administration of buprenorphine-naloxone for heroin dependence. Addiction 2007 Dec; 102(12): 1899–907PubMedCrossRefGoogle Scholar
  81. 81.
    Mintzer IL, Eisenberg M, Terra M, et al. Treating opioid addiction with buprenorphine-naloxone in community-based primary care settings. Ann Fam Med 2007 Mar–Apr; 5(2): 146–50PubMedCrossRefGoogle Scholar
  82. 82.
    Cunningham C, Giovanniello A, Sacajiu G, et al. Buprenorphine treatment in an urban community health center: what to expect. Fam Med 2008 Jul–Aug; 40(7): 500–6PubMedGoogle Scholar
  83. 83.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
  84. 84.
    Sullivan LE, Moore BA, Chawarski MC, et al. Buprenorphine/naloxone treatment in primary care is associated with decreased human immunodeficiency virus risk behaviors. J Subst Abuse Treat 2008 Jul; 35(1): 87–92PubMedCrossRefGoogle Scholar
  85. 85.
    Fiellin DA, Moore BA, Sullivan LE, et al. Long-term treatment with buprenorphine/naloxone in primary care: results at 2–5 years. Am J Addict 2008 Mar–Apr; 17(2): 116–20PubMedCrossRefGoogle Scholar
  86. 86.
    Amass L, Ling W, Freese TE, et al. Bringing buprenorphine-naloxone detoxification to community treatment providers: the NIDA Clinical Trials Network field experience. Am J Addict 2004; 13 Suppl. 1: S42–66PubMedCrossRefGoogle Scholar
  87. 87.
    Ling W, Amass L, Shoptaw S, et al. A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network. Addiction 2005 Aug; 100(8): 1090–100PubMedCrossRefGoogle Scholar
  88. 88.
    Ziedonis DM, Amass L, Steinberg ML, et al. Predictors of outcome for short-term medically supervised opioid withdrawal during a randomized, multicenter trial of buprenorphine-naloxone and clonidine in the NIDA clinical trials network drug and alcohol dependence. Drug Alcohol Depend 2009 Jan 1; 99(1–3): 28–36PubMedCrossRefGoogle Scholar
  89. 89.
    NIDA/SAMHSA. Short term opioid withdrawal using buprenorphine [online]. Available from URL: https://casat.unr.edu/mwattc/docs/Detox_Trainer_Guide.pdf [Accessed 2007 Jan 4]
  90. 90.
    Ling W, Hillhouse M, Domier C, et al. Buprenorphine tapering schedule and illicit opioid use. Addiction 2009 Feb; 104(2): 256–65PubMedCrossRefGoogle Scholar
  91. 91.
    Woody GE, Poole SA, Subramaniam G, et al. Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA 2008 Nov 5; 300(17): 2003–11PubMedCrossRefGoogle Scholar
  92. 92.
    Brigham GS, Amass L, Winhusen T, et al. Using buprenorphine short-term taper to facilitate early treatment engagement. J Subst Abuse Treat 2007 Jun; 32(4): 349–56PubMedCrossRefGoogle Scholar
  93. 93.
    Renzelli CM, Capretto NA. Less pain, more gain: buprenorphine-naloxone and patient retention in treatment. J Addict Dis 2006; 25(3): 97–104PubMedCrossRefGoogle Scholar
  94. 94.
    Collins ED, Horton T, Reinke K, et al. Using buprenorphine to facilitate entry into residential therapeutic community rehabilitation. J Subst Abuse Treat 2007 Mar; 32(2): 167–75PubMedCrossRefGoogle Scholar
  95. 95.
    Drugs and Poisons Regulation Group. Policy for maintenance pharmacotherapy for opioid dependence [online]. Available from URL: http://www.health.vic.gov.au/dpu/downloads/poilicy-opioid.pdf [Accessed 2006 Dec 8]
  96. 96.
    Vocci FJ, Acri J, Elkashef A. Medication development for addictive disorders: the state of the science. Am J Psychiatry 2005 Aug; 162(8): 1432–40PubMedCrossRefGoogle Scholar
  97. 97.
    Ling W, Cunningham-Rathner J, Rawson R. Diffusion of substance abuse treatment: will buprenorphine be a success? J Psychoactive Drugs 2004 May; Suppl. 2: 115–7PubMedCrossRefGoogle Scholar
  98. 98.
    Nielsen S, Dietze P, Lee N, et al. Concurrent buprenorphine and benzodiazepines use and self-reported opioid toxicity in opioid substitution treatment. Addiction 2007 Apr; 102(4): 616–22PubMedCrossRefGoogle Scholar
  99. 99.
    Gerra G, Borella F, Zaimovic A, et al. Buprenorphine versus methadone for opioid dependence: predictor variables for treatment outcome. Drug Alcohol Depend 2004 Jul 15; 75(1): 37–45PubMedCrossRefGoogle Scholar
  100. 100.
    Gerra G, Leonardi C, D’Amore A, et al. Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: a retrospective study. Prog Neuropsychopharmacol Biol Psychiatry 2006 Mar; 30(2): 265–72PubMedCrossRefGoogle Scholar
  101. 101.
    Simojoki K, Vorma H, Alho H. A retrospective evaluation of patients switched from buprenorphine (Subutex) to the buprenorphine/naloxone combination (Suboxone). Subst Abuse Treat Prev Policy 2008 Jun 17; 3: 16PubMedCrossRefGoogle Scholar
  102. 102.
    Gowing L, Ali R, White J. Buprenorphine for the management of opioid withdrawal. Cochrane Database Syst Rev 2006 Apr 19; (2): CD002025Google Scholar
  103. 103.
    Fiellin DA. Treatment of adolescent opioid dependence: no quick fix. JAMA 2008 Nov 5; 300(17): 2057–9PubMedCrossRefGoogle Scholar
  104. 104.
    Kleber HD. Pharmacologic treatments for opioid dependence: detoxification and maintenance options. Dialogues Clin Neurosci 2007; 9(4): 455–70PubMedGoogle Scholar
  105. 105.
    Doran CM. Buprenorphine, buprenorphine/naloxone and methadone maintenance: a cost-effectiveness analysis. Expert Rev Pharmacoeconomics Outcomes Res 2005; 5(5): 583–91CrossRefGoogle Scholar
  106. 106.
    Raisch DW, Fudala PJ, Saxon AJ, et al. Pharmacists’ and technicians’ perceptions and attitudes toward dispensing buprenorphine/naloxone to patients with opioid dependence. J Am Pharm Assoc 2005 Jan–Feb; 45(1): 23–32CrossRefGoogle Scholar
  107. 107.
    Finch JW, Kamien JB, Amass LA. Two-year experience with buprenorphine/naloxone (Suboxone) for maintenance treatment of opioid dependence within a private practice setting. J Addic Med 2007 Jun; 1(2): 104–10CrossRefGoogle Scholar

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

Personalised recommendations