Skip to main content
PMC home page
International Journal of Methods in Psychiatric Research logoLink to International Journal of Methods in Psychiatric Research
. 2006 Jan 6;14(1):14–28. doi: 10.1002/mpr.14

Buprenorphine and methadone in the treatment of opioid dependence: methods and design of the COBRA study

Hans‐Ulrich Wittchen 1,✉, Sabine M Apelt 1, Gerhard Bühringer 2, Markus Gastpar 3, Markus Backmund 4, Jörg Gölz 5, Michael R Kraus 6, Felix Tretter 7, Jens Klotsche 1, Jens Siegert 1, David Pittrow 8, Michael Soyka 9
PMCID: PMC6878433  PMID: 16097397

Abstract

Buprenorphine and methadone are the two established substitution drugs licensed in many countries for the treatment of opioid dependence. Little is known, however, about how these two drugs are applied and how they work in clinical practice. In this paper we present the aims, methods, design and sampling issues of a collaborative multi‐stage epidemiological study (COBRA) to address these issues.

Based on a nationally representative sample of substitution physicians, the study is designed as an observational, naturalistic study, consisting of three major parts. The first part was a national survey of substitution doctors (prestudy, n = 379 doctors). The second part was a cross‐sectional study (n = 223 doctors), which consisted of a target‐week assessment of 2,694 consecutive patients to determine (a) the severity and problem profiles and treatment targets; (b) the choice and dosage scheme of the substitution drug; (c) past and current interventions, including treatment of comorbid hepatitis C; and (d) cross‐sectional differences between the two drugs with regard to comorbidity, clinical course, acceptance/compliance and social integration. The third part consists of a prospective‐longitudinal cohort study of 48 methadone‐treated and 48 buprenorphine‐treated patients. The cohort is followed up over a period of 12 months to investigate whether course and outcome of the patients differ by type or treatment received in terms of clinical, psychosocial, pharmaco‐economic and other related measures. The response rate among substitution doctors was 57.1%; that among eligible patients was 71.7%. Comparisons with the federal registers reveal that the final samples of doctors and patients may be considered nationally representative with regard to regional distribution, training, type of setting as well as the frequency of patients treated with buprenorphine or methadone. The COBRA study provides a unique comprehensive database, informing about the natural allocation and intervention processes in routine care and about the course and outcome of patients treated with buprenorphine or methadone. Copyright © 2005 Whurr Publishers Ltd.

Keywords: methadone, buprenorphine, epidemiology, opioid dependence, hepatitis C, course, outcome

Full Text

The Full Text of this article is available as a PDF (267.2 KB).

References

  1. Brooks R, Rabin R, de Charro F. (eds). The Measurement and Valuation of Health Status using EQ‐5D: A European Perspective. Amsterdam: Kluwer Academic Publishers, 2003. [Google Scholar]
  2. Carey KB, Purnine DM, Maisto SA, Carey MP. Assessing readiness to change substance abuse: A critical review of instruments. Clinical Psychology: Science and Practice 1999; 6: 245–366. [Google Scholar]
  3. Christl B, Gerlach R. Fragebogen für substituierende Ärzte/Ärztinnen (Methadone‐Buprenorphine staff questionnaire. Caplehorn JRM 2002). Dresden: Technical University Dresden, Institute of Clinical Psychology and Psychotherapy, 2003. [Google Scholar]
  4. Farell M, Howes S, Verster A, Davoli M, Solberg U, Greenwood G, Robertson K. (eds). Reviewing Current Practice in Drug‐substitution Treatment in the European Union. Insights 3, EMCDDA Series. Luxembourg: Office for Official Publications of the European Communities, 2000. [Google Scholar]
  5. Gerra G, Borella F, Zaimovic A, Moi G, Bussandri M, Bubici C, Bertacca S. Buprenorphine versus methadone for opioid dependence: predictor variables for treatment outcome. Drug Alcohol Depend 2004; 75(1): 37–45. [DOI] [PubMed] [Google Scholar]
  6. Gossop M. The development of a short opiate withdrawal scale (SOWS). Addict Behav 1990; 15(5): 487–90. [DOI] [PubMed] [Google Scholar]
  7. Groß A, Soyka M. Buprenorphin—ein neuer Ansatz in der Pharmakotherapie opiatabhängiger Patienten (Buprenorphine – a new approach to pharmacotherapy of opiate‐addicted patients). Suchtmedizin 1999; 1(1): 5–14. [Google Scholar]
  8. Gsellhofer B, Küfner H, Vogt M, Weiler D. European Addiction Severity Index – EuropASI. Manual für Training und Durchführung [Manual for training and execution]. Stuttgart: Schneider Verlag, 1999. [Google Scholar]
  9. Guy W. Clinical global impressions In National Institute of Mental Health (ed.) ECDEU Assessment for Psychopharmacology. 1 edn. Rockville: National Institute of Mental Health, 1976, pp. 221–7. [Google Scholar]
  10. Johnson R‐E, Jaffe J‐H, Fudala P‐J. A controlled trial of buprenorphine treatment for opioid dependence. J Am Med Assoc 1992; 267(20): 2750–5. [PubMed] [Google Scholar]
  11. Johnson W‐A, Sterk C‐E. Late‐onset crack users: an emergent HIV risk group. J Acquir Immune Defic Syndr 2003; 33 Suppl 2: 229–32. [PubMed] [Google Scholar]
  12. Kakko J, Svanborg KD, Kreek MJ, Heilig M. 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): 662–8. [DOI] [PubMed] [Google Scholar]
  13. Kagerer S, Hock B, Wiese B, Lehnert R, Soyka M. Aufmerksamkeit, Konzentration und Gedächtnisleistung bei Opiatabhängigen unter Methadon und unter Buprenorphin (Attention, concentration and memory performance of opioid‐dependent patients under methadone and under buprenorphine). Suchtmed 2004; 6(1): 93–4. [Google Scholar]
  14. Kreek MJ. Biological correlates of methadone maintenance pharmocotherapy. Ann Med Interne (Paris) 1994; 145 Suppl 3: 9–14. [PubMed] [Google Scholar]
  15. Kuefner H, Vogt M, Indlekofer W. Test‐Manual PREDI 2.0. München: Bayerische Akademie für Suchtfragen in Forschung und Praxis BAS eV, 2001. [Google Scholar]
  16. Kuefner H, Hackmann K, Schnabel A, Soyka M. Optimierung der substitutionsgestützten Therapie Drogenabhängiger (OSTD): Entzugssymptome und Suchtverlangen in der ersten Einstellungswoche (Optimising substitution therapy for drug‐dependent patients (OSTD): withdrawal symptoms and craving in the first treatment week). Suchtmed 2004; 6(1): 95–7. [Google Scholar]
  17. Law FD, Nutt DJ. Maintenance buprenorphine for opioid users. Lancet 2003; 361(9358): 634–5. [DOI] [PubMed] [Google Scholar]
  18. Layson‐Wolf C, Goode JV, Small RE. Clinical use of methadone. J Pain Palliat Care Pharmacother 2002; 16(1): 29–59. [PubMed] [Google Scholar]
  19. Ling W, Charuvastra C, Kaim SC, Klett CJ. Methadyl acetate and methadone as maintenance treatments for heroin addicts. a veterans administration cooperative study. Arch Gen Psychiatry 1976; 33(6): 709–20. [DOI] [PubMed] [Google Scholar]
  20. Ling W, Wesson D‐R. Clinical efficacy of buprenorphine: comparisons to methadone and placebo. Drug Alcohol Depend 2003; 70(2 Suppl) : 49–57. [DOI] [PubMed] [Google Scholar]
  21. McLellan AG, Arndt IO, Metzger DS, Woody GE, O'Brien CP. The effects of psychosocial services in substance abuse treatment. J Am Med Assoc 1993; 269: 1953–9. [PubMed] [Google Scholar]
  22. Mattick RP, Ali R, White JM, O'Brien S, Wolk S, Danz C. Buprenorphine versus methadone maintenance therapy: a randomized double‐blind trial with 405 opioid‐dependent patients. Addiction 2003; 98(4): 441–52. [DOI] [PubMed] [Google Scholar]
  23. Mattick RP, Breen C, Kimber J, Davioli M. Methadone maintenance therapy versus no opioid treplacement therapy for opioid dependence (Cochrane Review). The Cochrane Library, 4. Chichester: Wiley, 2004. [Google Scholar]
  24. Mintzer M‐Z, Stitzer M‐L. Cognitive impairment in methadone maintenance patients. Drug Alcohol Depend 2002; 67(1): 41–51. [DOI] [PubMed] [Google Scholar]
  25. Petitjean S, Stohler R, Deglon JJ, Livoti S, Waldvogel D, Uehlinger C, Ladewig D. Double‐blind randomized trial of buprenorphine and methadone in opioid dependence. Drug Alcohol Depend 2001; 62(1): 97–104. [DOI] [PubMed] [Google Scholar]
  26. Poser S, Poser W. Medikamente – Missbrauch und Abhängigkeit: Entstehung. Verlauf. Behandlung (Pharmaceuticals and dependence: onset, course, treatment). Stuttgart: Thieme, 1996. [Google Scholar]
  27. San L, Cami J, Peri JM, Mata R, Porta M. Efficacy of clonidine, guanfacine and methadone in the rapid detoxification of heroin addicts: a controlled clinical trial. Br J Addict 1990; 85(1): 141–7. [DOI] [PubMed] [Google Scholar]
  28. Soyka M, Banzer K, Buchberger R, Völkl M, Naber D. Methadon‐Substitution Opiatabhängiger (Methadone substitution in opioid dependence). Nervenheilkunde 1997; 16: 347–52. [Google Scholar]
  29. Soyka M, Fischer G, Ladewig D, Blanke J, Nowak M, Poehlke T, Penning R, Liess H, Schütz C, Küfner H. Empfehlungen zur Anwendung von Buprenorphin (SUBUTEX) in der Substitutionsbehandlung opiatabhängiger Patienten in der Schweiz, Österreich und Deutschland (Konsensustexte) (Recommendations for buprenorphine (SUBUTEX) substitution therapy for opioid‐dependent patients in Switzerland, Austria and Germany (consensus reports)). Suchtmed 2000; 2(1): 43–53. [Google Scholar]
  30. Sutherland G, Edwards G, Taylor C, Phillips G, Gossop M, Brady R. The measurement of opiate dependence. Br J Addict 1986; 81(4): 485–94. [DOI] [PubMed] [Google Scholar]
  31. Vollmer H‐C, Krauth J. Therapie der Drogenabhängigkeit In Tretter F, Müller A. (eds) Psychologische Therapie der Sucht (Psychological Therapy of Addiction). Hogrefe; Göttingen, 2001, pp. 395–438. [Google Scholar]
  32. Walsh SL, Gilson SL, Jasinski DR, Stapleton JM, Phillips RL, Dannals RF, Schmidt J, Preston KL, Grayson R, Bigelow GE, Sullivan JT, Contoreggi C, London ED. Buprenorphine reduces cerebral glucose metabolism in polydrug abusers. Neuropsychopharmacology 1994; 10: 157–70. [DOI] [PubMed] [Google Scholar]
  33. Waal H, Haga E. Maintenance Treatment of Heroin Addiction: Evidence at the Crossroads. Oslo: Cappelen Akademisk Forlag, 2003. [Google Scholar]
  34. Wittchen H‐U. Reliability and validity studies of the WHO‐Composite International Diagnostic Interview (CIDI): a critical review. Journal of Psychiatric Research 1994a; 28(1): 57–84. [DOI] [PubMed] [Google Scholar]
  35. Wittchen H‐U, Pfister, H . DIA‐X‐Interviews: Manual für Screening‐Verfahren und Interview (Manual for screening procedure and interview); Ergänzungsheft (DIA‐X‐12 Monate) (Supplement (DIA‐X 12 months)). Frankfurt: Swets and Zeitlinger, 1997. [Google Scholar]
  36. Wittchen H‐U, Lachner G, Wunderlich U, Pfister H. Test‐retest reliability of the computerized DSM‐IV Version of the Munich‐Composite International Diagnostic Interview (M‐CIDI). Social Psychiatry and Psychiatric Epidemiology 1998; 33(11): 568–78. [DOI] [PubMed] [Google Scholar]
  37. Wittchen H‐U, Höfler M, Meister W. Prevalence and recognition of depressive syndromes in German primary care settings: poorly recognized and treated? International Clinical Psychopharmacology 2001; 16(3): 121–35. [DOI] [PubMed] [Google Scholar]
  38. Wittchen H‐U, Apelt SM, Christl B, Hagenau K, Groß A, Klotsche J, Soyka M. Die Versorgungspraxis der Substitutionstherapie Opiatabhängiger (COBRA) [The practice of supply in the substitution therapy for opiate addicts (COBRA)]. Suchtmedizin in Forschung und Praxis 2004; 6(1): 80–7. [Google Scholar]

Articles from International Journal of Methods in Psychiatric Research are provided here courtesy of Wiley

RESOURCES