Open Access Open Access  Restricted Access Subscription or Fee Access

A pilot study about the feasibility and cost-effectiveness of electronic compliance monitoring in substitution treatment with buprenorphine—naloxone combination

Ulrich Tacke, MD, PhD, Hanna Uosukainen, MSci (Pharm), Marjo Kananen, BSci (Pharm), Kirsi Kontra, Pharm Lic, Hannu Pentikäinen, MD


Objectives: The purpose of the study was to investigate whether or not compliance monitoring by microchip could offer a feasible method for reducing abuse and/or diversion of medication from unsupervised substitution treatment for opioid addiction.
Design: Naturalistic, 4-week pilot study in out patients.
Patients and interventions: All our patients (N = 12) on buprenorphine—naloxone combination (Suboxone®) received their medication for 6 days in a compliance-monitoring device (PharmaDDSi®, StoraEnso), which registers date and time of tablet removal. Patients were instructed to take all tablets as one dose. Time cues were displayed and discussed with the patients during their weekly visits for supervised drug administration and counseling.
Main outcome measures: Regularity of registered time cues, treatment costs in comparison with routine treatment, patients’ answers from a questionnaire on acceptability, and effect on drug diversion.
Results: Six patients showed good compliance, in two patients irregularities were minor, but in two others lack of adherence to treatment instructions was detected. Patients with several comorbid psychiatric diagnoses showed on an average the longest intervals between removal of first and last tablet of the daily dose. One-fourth of the patients reported that compliance monitoring had helped to avoid diversion. Total cost savings during the 4-week period was a reduction of 39 percent, which was mainly due to fewer visits to the clinic.
Conclusions: Compliance monitoring by PharmaDDSI® with weekly feedback was well accepted and subjectively increased compliance with substitution treatment. Future studies will show whether a technical solution for compliance monitoring in real time can help to reduce drug abuse and noncompliance in substitution treatment and other opioid treatments.


compliance monitoring, microchip, buprenorphine, naloxone, substitution treatment

Full Text:



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. 2003; 361(9358): 662-668.

Davids E, Gastpar M: Buprenorphine in the treatment of opioid dependence. Eur Neuropsychopharmacol. 2004; 14(3): 209-216.

Amato L, Davoli MCAP, Ferri M, et al.: An overview of systematic reviews of the effectiveness of opiate maintenance therapies: Available evidence to inform clinical practice and research. J Subst Abuse Treat. 2005; 28(4): 321-329.

Mattick RP, Kimber J, Breen C, et al.: Buprenorphine maintenance versus placebo or methadone aintenance for opioid dependence (Review). Cochrane Database Syst Rev. 2009; 1: CD002207.

Obadia Y, Perrin V, Feroni I, et al.: Injecting misuse of buprenorphine among French drug users. Addiction. 2001; 96(2): 267-272.

Tacke U: Abuse of buprenorphine by intravenous injection–The french connection. Addiction. 2002; 97(10): 1355.

Alho H, Sinclair D, Vuori E, et al.: Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Drug Alcohol Depend. 2007; 88(1): 75-78.

European Monitoring Centre for Drugs and Drug Addiction (EMCDDA): 2008 Annual report: The state of the drugs problem in Europe. Available at Accessed April 10, 2009.

European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and STAKES: National report 2007: Finland: National focal point, October 2007. Available at Accessed April 28, 2009.

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. 2003; 69: 175-181.

Jenkinson RA, Clark NC: Buprenorphine diversion and injection in Melbourne, Australia: An emerging issue? Addiction. 2005; 100(2): 197-205.

Winstock AR, Bell J: Clinical guidelines, assessing suitability for unsupervised medication doses in the treatment of opioid dependency. The Royal Australasian College of Physicians, Adult Medicine Division, Australasian Chapter of Addiction Medicine 2006. Available at Accessed November 13, 2008.

Smith MY, Baily JE, Woody GE, et al.: Abuse of buprenorphine in the United States 2003-2005. J Addict Dis. 2007; 26(3): 107-111.

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; 349(10): 949-958.

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; 141(1): 37-46.

Johnson RE, McCagh JC: Buprenorphine and naloxone for heroin dependence. Curr Psychiatry Rep. 2000; 2: 519-526.

Stoller KB, Bigelow GE, Walsh SL, et al.: Effects of buprenorphine/naloxone in opioid-dependent humans. Psychopharmacology. 2001; 154(3): 230-242.

Strain EC, Stoller K, Walsh SL, et al.: Effects of buprenorphine versus buprenorphine/naloxone tablets in non-dependent opioid abusers. Psychopharmacology. 2000; 148(4): 374-383.

Comer SD, Collins ED: Self-Administration of intravenous buprenorphine and the buprenorphine/naloxone combination by recently detoxified heroin abusers. J Pharmacol Exp Ther. 2002; 303(2): 695-703.

Bruce RD, Govindasamay S, Sylla L, et al.: Lack of reduction in buprenorphine injection after introduction of co-formulated buprenorphine/naloxone to the Malaysian market. Am J Drug Alcohol Abuse. 2009; 35(2): 68-72.

Winstock AR, Lea T, Jackson AP: Methods and motivations for buprenorphine diversion from public opioid substitution treatment clinics. J Addict Dis. 2009; 28(1): 57-63.

MacAleer SD, Mills RJ, Polack T, et al: Pharmacokinetics of high-dose buprenorphine following single administration of sublingual tablet formulations in opioid naïve healthy male volunteers under a naltrexone block. Drug Alcohol Depend. 2003; 72(1): 75-83.

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; 23: 311-317.

Amass L, Bickel WK, Crean JP, et al.: Alternate-day buprenorphine dosing is preferred to daily dosing by opioiddependent humans. Psychopharmacology (Berl). 1998; 136(3): 217-225.

Marsch LA, Bickel WK, Badger GJ, et al.: Buprenorphine treatment for opioid dependence: The relative efficacy of daily, twice and thrice weekly dosing. Drug Alcohol Depend. 2005; 77(2): 195-204.

Latt N, Conigrave K, Saunders JB, et al. (eds.): Addiction Medicine. Oxford: Oxford University Press, 2009.

Amass L, Kamien JB, Mikulich SK: Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine-naloxone tablet. Drug Alcohol Depend. 2000; 58(1-2): 143-152.

Ministry of Social Affairs and Health: Decree of the Ministry of Social Affairs and Health on the detoxification and substitution treatment of opioid addicts with certain medicinal products, No. 33/2008. Available at Accessed April 10, 2009.

Fudala PJ, Johnson RE: Development of opioid formulations with limited diversion and abuse potential. Drug Alcohol Depend. 2005; 83(1): S40-S47.

Katz NP, Adams EH, Benneyan JC, et al.: Foundations of opioid risk management. Clin J Pain. 2007; 23(2): 103-118.

Hall W, Degenhardt L (editorial): Regulating opioid prescribing to provide access to effective treatment while minimizing diversion: An overdue topic for research. Addiction 2007; 102: 1685-1688.

Kreek MJ, Nielsen DA, Butelman ER, et al.: Genetic influences and impulsivity, risk taking, stress resposivity and vulnerability to drug abuse and addiction. Nat Neurosci. 2005; 8(11): 1450-1457.

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; 102(12): 1899-1907.

Strain EC, Brooner RK, Bigelow GE: Clustering of multiple substance use and psychiatric diagnoses in opiate addicts. Drug Alcohol Depend. 1991; 74: 37-43.

McLellan AT: Psychiatric severity as a predictor of outcome from substance abuse treatments. In Meyer RE (ed.): Psychopathology and Addictive Disorders. NewYork, NY: Guilford Press, 1986: 97-139.

Compton WM, Volkow ND: Major increases in opioid analgesic abuse in the United States: Concerns and strategies. Drug Alcohol Depend. 2006; 81(2): 103-107.



  • There are currently no refbacks.