0
0

Chapter 21. Buprenorphine Maintenance

Eric C. Strain, M.D.; Michelle R. Lofwall, M.D.
DOI: 10.1176/appi.books.9781585623440.352360

Sections

Excerpt

Buprenorphine is a partial opioid agonist and antagonist that was synthesized in 1973 and initially used for the treatment of pain. In the 1990s there developed growing evidence that buprenorphine was also efficacious for the treatment of opioid dependence; individuals addicted to heroin submitted fewer opioid-positive urine tests and reported less participation in illegal activities while receiving sublingual buprenorphine maintenance treatment (Bickel et al. 1988b; Johnson et al. 1992, 1995b; Ling et al. 1996, 1998; Schottenfeld et al. 1997; Strain et al. 1994). Outside of the United States, several countries, such as France, made buprenorphine available to general practitioners to prescribe in office-based settings for the treatment of opioid addiction and results also were positive (Strain et al. 2003). However, in the United States during the 1990s, the Harrison Narcotic Act of 1914 continued to make it illegal for physicians to prescribe opioids in an office-based setting for opioid addiction. Methadone remained the primary opioid maintenance medication treatment, but its availability was limited and many individuals who were addicted to opioids remained out of treatment despite having sought treatment.

Your session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 21–1. Hypothetical dose response curve for a partial and full opioid agonist.

FIGURE 21–2. Sample treatment contract.
Table Reference Number
TABLE 21–1. Physician qualifications for buprenorphine office-based treatment
Table Reference Number
TABLE 21–2. DSM-IV-TR criteria for substance dependence
Table Reference Number

Buprenorphine is currently a Schedule III medication that is approved for opioid maintenance treatment and that can be used in an office-based setting.

Buprenorphine can be prescribed by a qualified physician that obtains a waiver and X number from the U.S. Drug Enforcement Administration.

Buprenorphine is a partial opioid agonist, which means that it stimulates the opioid receptor, but that there is a limit (ceiling) to the degree of opioid effects (e.g., respiratory depression) that it can produce, thereby enhancing its safety profile.

Naloxone is included in sublingual buprenorphine tablets to decrease the misuse and abuse of the drug; if tablets are tampered with and injected, the naloxone will precipitate opioid withdrawal among persons with opioid physical dependence. If tablets are taken as prescribed by the sublingual route there is little absorption of naloxone.

Buprenorphine is metabolized by the liver cytochrome P450 3A4 enzyme system so inducers or inhibitors of P450 3A4 could interact with buprenorphine's metabolism.

A comprehensive initial evaluation is required before beginning buprenorphine treatment, and treatment requirements (e.g., random urine toxicology screens and/or random pill counts) and expectations should be explicitly communicated between physician and patient prior to commencing treatment.

Effective treatment includes addressing medical and psychiatric comorbidities and rehabilitation of the patient.

Buprenorphine is not currently approved for the treatment of opioid dependence in pregnancy, but early research findings are promising for its use in this population.

Office-based buprenorphine maintenance treatment has the potential to substantially increase the availability of treatment for opioid addiction, but buprenorphine's actual impact will be determined largely by the number of physicians willing to treat these patients.

References

Alford DP, Compton P, Samet JH: Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med 144:127–134, 2006; erratum in Ann Intern Med 144:460, 2006
 
Baker JR, Best AM, Pade PA, et al: Effect of buprenorphine and antiretroviral agents on the QT interval in opioid-dependent patients. Ann Pharmacother 40:392–396, 2006
[PubMed]
 
Berson A, Gervais A, Cazals D, et al: Hepatitis after intravenous buprenorphine misuse in heroin addicts. J Hepatol 34:346–350, 2001
[PubMed]
 
Bickel WK, Stitzer ML, Bigelow GE, et al: Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans. J Pharmacol Exp Ther 247:47–53, 1988a
 
Bickel WK, Stitzer ML, Bigelow GE, et al: A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts. Clin Pharmacol Ther 43:72–78, 1988b
 
Brooner RK, King VL, Kidorf M, et al: Psychiatric and substance use comorbidity among treatment-seeking opioid abusers. Arch Gen Psychiatry 54:71–80, 1997
[PubMed]
 
Brooner RK, Kidorf M, King VL, et al: Behavioral contingencies improve counseling attendance in an adaptive treatment model. J Subst Abuse Treat 27:223–232, 2004
[PubMed]
 
Bruce RD, Altice FL: Three case reports of a clinical pharmacokinetic interaction with buprenorphine and atazanavir plus ritonavir. AIDS 20:783–784, 2006
[PubMed]
 
Bruce RD, McCance-Katz E, Kharasch ED, et al: Pharmacokinetic interactions between buprenorphine and antiretroviral medications. Clin Infect Dis 43 (suppl 4):S216–S223, 2006
 
Cheskin LJ, Fudala PJ, Johnson RE: A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids. Drug Alcohol Depend 36:115–121, 1994
[PubMed]
 
Cohen MJM, Jasser SA: Pain management in addicted patients, in The Treatment of Opioid Dependence. Edited by Strain EC, Stitzer ML. Baltimore, MD, The Johns Hopkins University Press, 2006, pp 527–546
 
Comer SD, Collins ED, Fischman MW: Buprenorphine sublingual tablets: effects on IV heroin self-administration by humans. Psychopharmacology (Berl) 154:28–37, 2001
[PubMed]
 
Cone EJ, Gorodetzky CW, Yousefnejad D, et al: The metabolism and excretion of buprenorphine in humans. Drug Metab Dispos 12:577–581, 1984
[PubMed]
 
Correia CJ, Walsh SL, Bigelow GE, et al: Effects associated with double-blind omission of buprenorphine/naloxone over a 98-h period. Psychopharmacology (Berl) 189:297–306, 2006
[PubMed]
 
Cozza KL, Armstrong SC, Oesterheld JR: Concise Guide to Drug Interaction Principles for Medical Practice: Cytochrome P450s, UGTs, P-Glycoproteins, 2nd Edition. Washington, DC, American Psychiatric Publishing, 2003
 
Fiellin DA, Strain EC: Office-based treatment with buprenorphine and other medications, in The Treatment of Opioid Dependence. Edited by Strain EC, Stitzer ML. Baltimore, MD, The Johns Hopkins University Press, 2006, pp 253–276
 
Fiellin DA, Pantalon MV, Charwaski MC, et al: Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. N Engl J Med 355:365–374, 2006
[PubMed]
 
Fingerhood MI, Jasinski DR, Sullivan JT: Prevalence of hepatitis C in a chemically dependent population. Arch Intern Med 153:2025–2030, 1993
[PubMed]
 
Fingerhood MI, Thompson MR, Jasinski DR: A comparison of clonidine and buprenorphine in the outpatient treatment of opiate withdrawal. Subst Abus 22:193–199, 2001
[PubMed]
 
Fischer G, Ortner R, Rohrmeister K, et al: Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study. Addiction 101:275–281, 2006
[PubMed]
 
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 349:949–958, 2003
[PubMed]
 
Galanter M, Dermatis H, Resnick R, et al: Short-term buprenorphine maintenance: treatment outcome. J Addict Dis 22:39–49, 2003
[PubMed]
 
Galanter M, Dermatis H, Glickman L, et al: Network therapy: decreased secondary opioid use during buprenorphine maintenance. J Subst Abuse Treat 26:313–318, 2004
[PubMed]
 
Girotra S, Kumar S, Rajendran KM, et al: Comparison of caudal morphine and buprenorphine for post-operative analgesia in children. Eur J Anaesthesiol 10:309–312, 1993
[PubMed]
 
Gossop M, Griffiths P, Bradley B, et al: Opiate withdrawal symptoms in response to 10-day and 21-day methadone withdrawal programmes. Br J Psychiatry 154:360–363, 1989
[PubMed]
 
Harcus AW, Ward AE, Smith DW, et al: The monitored release of buprenorphine: results in the young. J Int Med Res 8:153–155, 1980
[PubMed]
 
Higgins ST, Silverman K (eds): Motivating Behavior Change Among Illicit-Drug Abusers. Washington, DC, American Psychological Association, 1999
 
Huang P, Kehner GB, Cowan A, et al: Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist. J Pharmacol Exp Ther 297:688–695, 2001
[PubMed]
 
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 35:501–516, 1978
[PubMed]
 
Jasinski DR, Boren JJ, Henningfield JE, et al: Progress report from the NIDA Addiction Research Center. Baltimore, Maryland. NIDA Res Monogr 49:69–76, 1984
[PubMed]
 
Johnson RE, Jaffe JH, Fudala PJ: A controlled trial of buprenorphine treatment for opioid dependence. JAMA 267:2750–2755, 1992
[PubMed]
 
Johnson RE, Eissenberg T, Stitzer ML, et al: Buprenorphine treatment of opioid dependence: clinical trial of daily versus alternate-day dosing. Drug Alcohol Depend 40:27–35, 1995a
 
Johnson RE, Eissenberg T, Stitzer ML, et al: A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence. Drug Alcohol Depend 40:17–25, 1995b
 
Johnson RE, Chutuape MA, Strain EC, et al: A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med 343:1290–1297, 2000
[PubMed]
 
Johnson RE, Jones HE, Fischer G: Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend 70 (suppl 2):S87–S101, 2003
 
Jones HE, Johnson RE, Jasinski DR, et al: Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Drug Alcohol Depend 79:1–10, 2005
[PubMed]
 
Jones HE, Johnson RE, Milio L, et al: Post-cesarean pain management of patients maintained on methadone or buprenorphine. Am J Addict 15:258–259, 2006
[PubMed]
 
Kakko J, Svanborg KD, Kreek MJ, et al: 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet 361:662–668, 2003
[PubMed]
 
Kidorf M, Stitzer ML: Contingent access to clinic privileges reduces drug abuse in methadone maintenance patients, in Motivating Behavior Change Among Illicit-Drug Abusers. Edited by Higgins ST, Silverman K. Washington, DC, American Psychological Association, 1999
 
Kintz P: Deaths involving buprenorphine: a compendium of French cases. Forensic Sci Int 121:65–69, 2001
[PubMed]
 
Kosten TR, Kleber HD: Buprenorphine detoxification from opioid dependence: a pilot study. Life Sci 42:635–641, 1988
 
Kosten TR, Morgan C, Kleber HD: Phase II clinical trials of buprenorphine: detoxification and induction onto naltrexone. NIDA Res Monogr 121:101–119, 1992
[PubMed]
 
Lange WR, Fudala PJ, Dax EM, et al: Safety and side-effects of buprenorphine in the clinical management of heroin addiction. Drug Alcohol Depend 26:19–28, 1990
[PubMed]
 
Lavelle TL, Hammersley R, Forsyth A: The use of buprenorphine and temazepam by drug injectors. J Addict Dis 10:5–14, 1991
[PubMed]
 
Ling W, Charuvastra C, Collins JF, et al: Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial. Addiction 93: 475–486, 1998
[PubMed]
 
Ling W, Wesson DR: Clinical efficacy of buprenorphine: comparisons to methadone and placebo. Drug Alcohol Depend 70 (Suppl 2):S49–S57, 2003
 
Ling W, Wesson DR, Charuvastra C, et al: A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Arch Gen Psychiatry 53:401–407, 1996
[PubMed]
 
Lofwall MR, Stitzer ML, Bigelow GE, et al: Comparative safety and side effect profiles of buprenorphine and methadone in the outpatient treatment of opioid dependence. Addictive Disorders and Their Treatment 4:49–64, 2005
 
Marquet P: Pharmacology of high-dose buprenorphine, in Buprenorphine Therapy of Opiate Addiction. Edited by Kintz P, Marquet P. Totowa, NJ, Humana Press, 2002, pp 1–11
 
Marsch LA, Bickel WK, Badger GJ, et al: Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial. Arch Gen Psychiatry 62:1157–1164, 2005
[PubMed]
 
Mattick RP, Kimber J, Breen C, et al: Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews, Issue 2, Article No: CD002207, 2003
 
McCance-Katz EF, Rainey PM, Friedland G, et al: Effect of opioid dependence pharmacotherapies on zidovudine disposition. Am J Addict 10:296–307, 2001
[PubMed]
 
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 43 (suppl 4):S224–S234, 2006a
 
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 43 (suppl 4):S235–S246, 2006b
 
McLellan AT, Arndt IO, Metzger DS, et al: The effects of psychosocial services in substance abuse treatment. JAMA 269:1953–1959, 1993
[PubMed]
 
McLellan AT, Lewis DC, O'Brien CP, et al: Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA 284:1689–1695, 2000
[PubMed]
 
McNicholas L (ed): Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. TIP Series #40 (DHHS Publ No SMA-04-3939). Rockville, MD, U.S. Department of Health and Human Services, 2004
 
Mello NK, Mendelson JH: Buprenorphine suppresses heroin use by heroin addicts. Science 207:657–659, 1980
[PubMed]
 
Mello NK, Mendelson JH, Kuehnle JC, et al: Buprenorphine effects on human heroin self-administration: an operant analysis. J Pharmacol Exp Ther 223:30–39, 1982
[PubMed]
 
Mendelson J, Jones RT, Fernandez I, et al: Buprenorphine and naloxone interactions in opiate-dependent volunteers. Clin Pharmacol Ther 60:105–114, 1996
[PubMed]
 
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 74:205–209, 2004
[PubMed]
 
Novick DM, Richman BL, Friedman JM, et al: The medical status of methadone maintenance patients in treatment for 11–18 years. Drug Alcohol Depend 33:235–245, 1993
[PubMed]
 
Ohtani M, Kotaki H, Sawada Y, et al: Comparative analysis of buprenorphine- and norbuprenorphine-induced analgesic effects based on pharmacokinetic-pharmacodynamic modeling. J Pharmacol Exp Ther 272:505–510, 1995
[PubMed]
 
Petry NM, Bickel WK, Piasecki D, et al: Elevated liver enzyme levels in opioid-dependent patients with hepatitis treated with buprenorphine. Am J Addict 9:265–269, 2000
[PubMed]
 
Resnick RB, Galanter M, Psycha C, et al: Buprenorphine: an alternative to methadone for heroin dependence treatment. Psychopharmacol Bull 28:109–113, 1992
[PubMed]
 
Reynaud M, Petit G, Potard D, et al: Six deaths linked to concomitant use of buprenorphine and benzodiazepines. Addiction 93:1385–1392, 1998
[PubMed]
 
Robinson GM, Dukes PD, Robinson BJ, et al: The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Drug Alcohol Depend 33:81–86, 1993
[PubMed]
 
Rosen MI, Wallace EA, McMahon TJ, et al: Buprenorphine: duration of blockade of effects of intramuscular hydromorphone. Drug Alcohol Depend 35:141–149, 1994
[PubMed]
 
San L, Tremoleda J, Ollé JM, et al: Prevalence of buprenorphine use by heroin addicts undergoing treatment. Med Clin (Barc) 93:645–648, 1989
[PubMed]
 
Schottenfeld RS, Pakes JR, Oliveto A, et al: Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Arch Gen Psychiatry 54:713–720, 1997
[PubMed]
 
Schuh KJ, Walsh SL, Stitzer ML: Onset, magnitude and duration of opioid blockade produced by buprenorphine and naltrexone in humans. Psychopharmacology (Berl) 145:162–174, 1999
[PubMed]
 
Senay EC, Dorus W, Goldberg F, et al: Withdrawal from methadone maintenance. Rate of withdrawal and expectation. Arch Gen Psychiatry 34:361–367, 1977
[PubMed]
 
Sigmon SC, Wong CJ, Chausmer AL, et al: Evaluation of an injection depot formulation of buprenorphine: placebo comparison. Addiction 99:1439–1449, 2004
[PubMed]
 
Sigmon SC, Moody DE, Nuwayser ES, et al: An injection depot formulation of buprenorphine: extended bio-delivery and effects. Addiction 101:420–432, 2006
[PubMed]
 
Strain EC: Clinical use of buprenorphine, in The Treatment of Opioid Dependence. Edited by Strain EC, Stitzer ML. Baltimore, MD, The Johns Hopkins University Press, 2006a, pp 230–252
 
Strain EC: Pharmacology of buprenorphine, in The Treatment of Opioid Dependence. Edited by Strain EC, Stitzer ML. Baltimore, MD, The Johns Hopkins University Press, 2006b, pp 213–229
 
Strain EC, Preston KL, Liebson IA, et al: Acute effects of buprenorphine, hydromorphone and naloxone in methadone-maintained volunteers. J Pharmacol Exp Ther 261:985–993, 1992
[PubMed]
 
Strain EC, Stitzer ML, Liebson IA, et al: Comparison of buprenorphine and methadone in the treatment of opioid dependence. Am J Psychiatry 151:1025–1030, 1994
[PubMed]
 
Strain EC, Preston KL, Liebson IA, et al: Buprenorphine effects in methadone-maintained volunteers: effects at two hours after methadone. J Pharmacol Exp Ther 272:628–638, 1995
[PubMed]
 
Strain EC, Stitzer ML, Liebson IA, et al: Buprenorphine versus methadone in the treatment of opioid dependence: self-reports, urinalysis, and addiction severity index. J Clin Psychopharmacol 16:58–67, 1996
[PubMed]
 
Strain EC, Walsh SL, Preston KL, et al: The effects of buprenorphine in buprenorphine-maintained volunteers. Psychopharmacology (Berl) 129:329–338, 1997
[PubMed]
 
Strain EC, Walsh SL, Bigelow GE, et al: Blockade of hydromorphone effects by buprenorphine/naloxone and buprenorphine. Psychopharmacology (Berl) 159:161–166, 2002
[PubMed]
 
Strain EC, Clark HW, Auriacombe M, et al: Symposium XV French experience with buprenorphine. NIDA Res Monograph 183:134–141, 2003
 
Strain EC, Moody DE, Stoller KB, et al: Relative bioavailability of different buprenorphine formulations under chronic dosing conditions. Drug Alcohol Depend 74:37–43, 2004
[PubMed]
 
Sullivan LE, Barry D, Moore BA, et al: A trial of integrated buprenorphine/naloxone and HIV clinical care. Clin Infect Dis 43 (suppl 4):S184–S190, 2006
 
Sung HE, Richter L, Vaughan R, et al: Nonmedical use of prescription opioids among teenagers in the United States: trends and correlates. J Adolesc Health 37:44–51, 2005
[PubMed]
 
Umbricht-Schneiter A, Ginn DH, Pabst KM, et al: Providing medical care to methadone clinic patients: referral vs on-site care. Am J Public Health 84:207–210, 1994
[PubMed]
 
U.S. Food and Drug Administration: Drug label. 2002. Available online at: http://www.fda.gov/cder/foi/label/2002/20732lbl.pdf. Accessed December 3, 2007.
 
Vidal-Trecan G, Varescon I, Nabet N, et al: Intravenous use of prescribed sublingual buprenorphine tablets by drug users receiving maintenance therapy in France. Drug Alcohol Depend 69:175–181, 2003
[PubMed]
 
Walsh SL, Preston KL, Stitzer ML, et al: Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther 55:569–580, 1994
[PubMed]
 
Walsh SL, June HL, Schuh KJ, et al: Effects of buprenorphine and methadone in methadone-maintained subjects. Psychopharmacology (Berl) 119:268–276, 1995
[PubMed]
 
Wedam EF, Haigney MCP, et al: EKG QT-prolongation effects of methadone, LAAM, and buprenorphine in a randomized trial. Paper presented at conference of the College on Problems of Drug Dependencem San Juan, Puerto Rico, 2004
 
Zhang W, Ramamoorthy Y, Tyndale RF, et al: Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro. Drug Metab Dispos 31:768–772, 2003
[PubMed]
 
+

CME Activity

Add a subscription to complete this activity and earn CME credit.
Sample questions:
1.
Buprenorphine has a mixed mechanism of action at opioid receptors. What are its main opioid receptor effects?
2.
In the United States, buprenorphine is on which controlled substance schedule?
3.
Which statement regarding the pharmacokinetics of buprenorphine is false?
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Articles
Books
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 14.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 18.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 20.  >
Topic Collections
Psychiatric News
PubMed Articles
Where do we stand in the field of anti-abuse drug discovery? Expert Opin Drug Discov 2014;():1-4.doi:10.1517/17460441.2014.948415.
 
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation