Buprenorphine/naloxone versus methadone and lofexidine in community stabilisation and detoxification: A randomised controlled trial of low dose short-term opiate-dependent individuals

Abstract

Buprenorphine/naloxone, methadone and lofexidine are medications with utility in the treatment of opiate withdrawal. We report the first randomised controlled trial to compare the effects of these two medications on withdrawal symptoms and outcome during opiate induction/stabilisation and detoxification. A double-blind randomised controlled trial was conducted in an outpatient satellite clinic of a specialist drug service. Eighty opiate dependent individuals meeting DSM-IV criteria for opiate dependence, using ⩽ ½ g heroin smoked/chased or ¼ g heroin injected or ⩽ 30mg methadone, with ⩽ 3 years of opioid dependency, underwent a short-term opiate treatment programme involving induction/stabilisation on methadone 30mg or buprenorphine/naloxone 4mg/1mg, followed by detoxification (where the methadone group was assisted by lofexidine). The main outcome measures were urine drug screens for opiates and withdrawal and craving questionnaires. There were no overall differences in positive urine drug screens and drop-outs during any phase of the study. During induction/stabilisation, withdrawal symptoms subsided more slowly for buprenorphine/naloxone than for methadone, and craving was significantly higher in the buprenorphine/naloxone group (p<0.05, 95% confidence interval −3.5, −0.38). During detoxification, withdrawal symptoms were significantly greater and the peak of withdrawal was earlier for the methadone/lofexidine group than the buprenorphine/naloxone group (p<0.01, 95% confidence interval 3.0, 8.3). Methadone/lofexidine and buprenorphine/naloxone had comparable outcomes during rapid outpatient stabilisation and detoxification in low dose opiate users.

Keywords

Buprenorphine methadone lofexidine opiate withdrawal detoxification

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References

Akhurst

(1999) The use of lofexidine by drug dependency units in the United Kingdom. Eur Addict Res 5: 43–49.

APA (1994) Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association.

Bearn

Gossop

Strang

(1996) Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal. Drug Alcohol Depend 43: 87–91.

Bickel

Amass

(1995) Buprenorphine treatment of opioid dependence: A review. Exp Clin Psychopharmacol 3: 477–489.

Bickel

Amass

Crean

(1999) Buprenorphine dosing every 1, 2, or 3 days in opioid-dependent patients. Psychopharmacology (Berl) 146: 111–118.

Bickel

Amass

Higgins

(1997) Effects of adding behavioural treatment to opiate detoxification with buprenorphine. J Consult Clin Psychol 65: 803–810.

Bickel

Stitzer

Bigelow

(1988a) Buprenorphine: Dose-related blockade of opioid challenge effects in opioid dependent humans. J Pharm Exp Ther 247: 47–53.

Bickel

Stitzer

Bigelow

(1988b) A clinical trial of buprenorphine: Comparison with methadone in the detoxification of heroin addicts. Clin Pharmacol Ther 43: 72–78.

Bradley

Gossop

Phillips

(1987) The development of an opiate withdrawal scale (OWS). Br J Addict 82: 1139–1142.

10.

CADTH (2016) Buprenorphine/Naloxone Versus Methadone for the Treatment of Opioid Dependence: A Review of Comparative Clinical Effectiveness, Cost-Effectiveness and Guidelines. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health. Available at: https://www.cadth.ca/sites/default/files/pdf/htis/sep-2016/RD0032_Suboxone_Final.pdf (accessed 23 May 2017).

11.

Frazer

van Horn

Martin

(1961) Methods for evaluating addiction liability (A) “attitude” of opiate addicts towards opiate-like drugs, (b A short-term “direct” addiction test. J Pharm Exp Ther 133: 371–387.

12.

Gowing

Ali

White

(2009) Buprenorphine for the management of opioid withdrawal. Cochrane Database Syst Rev 3: CD002025.

13.

Herman

O’Brien

(1997) Clinical medications development for opiate addiction: Focus on non-opioids and opioid antagonists for the amelioration of opiate withdrawal symptoms and relapse prevention. Semin Neurosci 9: 158–172.

14.

Hussain

Farhat

Rather

(2015) Comparative trial to study the effectiveness of clonidine hydrochloride and buprenorphine-naloxone in opioid withdrawal - a hospital based study. J Clin Diagn Res 9: FC01–FC04.

15.

Kahan

Srivastava

Ordean

(2011) Buprenorphine: New treatment of opioid addiction in primary care. Can Fam Physician 57: 281–289.

16.

Kanof

PDK

Aronson

Ness

(1993) Organic mood syndrome associated with detoxification from methadone maintenance. Am J Psychiatry 150: 423–428.

17.

Law

Bailey

Allen

(1997) The feasibility of abrupt methadone-buprenorphine transfer in British opiate addicts in an outpatient setting. Addict Biol 2: 191–200.

18.

Law

Myles

Daglish

MRC

(2004) The clinical use of buprenorphine in opiate addiction: evidence and practice. Acta Neuropsychiatr 16: 246–274 (erratum at 2004, 16, 362).

19.

Lewis

(1985) Buprenorphine. Drug Alcohol Depend 14: 363–372.

20.

Lewis

(1995) Clinical pharmacology of buprenorphine in relation to its use as an analgesic. In: Cowan

Lewis

(eds) Buprenorphine Combatting Drug Abuse with a Unique Opioid. New York, NY: Wiley-Liss, pp.151–163.

21.

Ling

Amass

Shoptaw

; Buprenorphine Study Protocol Group (2005) 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 100: 1090–1100.

22.

McCaul

Stitzer

Bigelow

(1984) Contingency management interventions: Effects on treatment outcome during methadone detoxification. J Appl Behav Anal 17: 35–43.

23.

Myles

(1996) Alpha-2-adrenoceptors in addiction. J Psychopharmacol 10(Suppl. 3): 49–52.

24.

NICE (2007a) Methadone and Buprenorphine for the Management of Opioid Dependence. NICE Technology Appraisal 114. London: National Institute for Health and Clinical Excellence.

25.

NICE (2007b) Drug Misuse: Opioid Detoxification. NICE Clinical Guideline No. 52. London: National Institute for Health and Clinical Excellence.

26.

Nutt

(1997) Receptor pharmacology of buprenorphine. Res Clin Forum 19: 9–15.

27.

Orman

Keating

(2009) Buprenorphine/naloxone: A review of its use in the treatment of opioid dependence. Drugs 69: 577–607.

28.

Raistrick

West

Finnegan

(2005) A comparison of buprenorphine and lofexidine for community opiate detoxification: Results from a randomized controlled trial. Addiction 100: 1860–1867.

29.

Rance

Dickens

(1978) The influence of drug-receptor kinetics on the pharmacological and pharmo-kinetic profiles of buprenorphine. In: Van Ree

Pereniums

(eds) Characteristics and Function of Opioids. Amsterdam: Elsevier/North Holland Biomedical Press, pp.65–66.

30.

Rounsaville

Kosten

Kleber

(1985) Success and failure at outpatient opioid detoxification: Evaluating the process of clonidine- and methadone-assisted withdrawal. J Nerv Ment Dis 173: 103–110.

31.

Spear

(2014) Reducing readmissions to detoxification: An interorganizational network perspective. Drug Alcohol Depend 137: 76–82.

32.

Strain

Moody

Stoller

(2004) Relative bioavailability of different buprenorphine preparations under chronic dosing conditions. Drug Alcohol Depend 74: 37–43.

33.

Tetrault

Fiellin

(2012) Current and potential pharmacological treatment options for maintenance therapy in opioid-dependent individuals. Drugs 72: 217–228.

34.

Wright

Sheard

Adams

(2011) Comparison of methadone and buprenorphine for opiate detoxification (LEEDS trial): A randomised controlled trial. Br J Gen Pract 61: e772– e780.

35.

Yokell

Zaller

Green

(2011) Buprenorphine and buprenorphine/naloxone diversion, misuse, and illicit use: An international review. Curr Drug Abuse Rev 4: 28–41.

36.

Miotto

Akerele

(2008) A phase 3 placebo-controlled, double blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Drug Alcohol Depend 97: 158–168.

37.

Ziaaddini

Nasirian

Nakhaei

(2010) Comparison of buprenorphine and clonidine in heroin detoxification. Addict Health 2: 1–2.

38.

Ziedonis

Amass

Steinberg

(2009) 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 99: 28–36.

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