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Heroin-assisted treatment for opioid dependence: Randomised controlled trial

  • Christian Haasen (a1), Uwe Verthein (a1), Peter Degkwitz (a1), Juergen Berger (a2), Michael Krausz (a3) and Dieter Naber (a3)...

Heroin-assisted treatment has been found to be effective for people with severe opioid dependence who are not interested in or do poorly on methadone maintenance.


To study heroin-assisted treatment in people on methadone who continue intravenous heroin and in those who are heroin dependent but currently not in treatment.


In an open-label multicentre randomised controlled trial, 1015 people with heroin dependence received a variable dose of injectable heroin (n=515) or oral methadone (n=500) for 12 months. Two response criteria, improvement of physical and/or mental health and decrease in illicit drug use, were evaluated in an intent-to-treat analysis.


Retention was higher in the heroin (67.2%) than in the methadone group (40.0%) and the heroin group showed a significantly greater response on both primary outcome measures. More serious adverse events were found in the heroin group, and were mainly associated with intravenous use.


Heroin-assisted treatment is more effective for people with opioid dependence who continue intravenous heroin while on methadone maintenance or who are not enrolled in treatment. Despite a higher risk, it should be considered for treatment resistance under medical supervision.

Corresponding author
Dr Christian Haasen, Centre for Interdisciplinary Addiction Research, Department of Psychiatry, University Medical Centre Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Email:
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Declaration of interest

None. Funding detailed in Acknowledgements.

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Ali, R., Auriacombe, M., Casas, M., et al (1999) Report of the external panel on the evaluation of the Swiss scientific studies of medically prescribed narcotics to drug addicts. Sucht, 45, 160–70.
Bammer, G., Dobler-Mikola, A., Fleming, P. M., et al (1999) Prescription heroin to dependent users: integrating science and politics. Science, 284, 12771278.
Blanken, P., Hendriks, V. M., Koeter, M. W., et al (2005) Matching of treatment-resistant heroin dependent patients to medical prescription of heroin or oral methadone treatment: results from two randomized controlled trials. Addiction, 100, 8995.
Bühringer, G., Adelsberger, F., Heinemann, A., et al (1997) Schtzverfahren und Schtzungen 1997 zum Umfang der Drogenproblematik in Deutschland [Estimation method and estimates 1997 on the extent of the drug problem in Germany]. Sucht, 43 (suppl. 2), 78143.
Darke, S., Ward, J., Zador, D., et al (1991) A scale for estimating the health status of opioid users. British Journal of Addiction, 86, 13171322.
Darke, S., Hall, W., Wodak, A., et al (1992) Development and validation of a multidimensional instrument for assessing outcome of treatment among opiate users: the Opiate Treatment Index. British Journal of Addiction, 87, 733742.
Derogatis, L. R. (1983) SCL-90-R: Administration, Scoring and Procedures (manual II). Clinical Psychometric Research.
Dijkgraaf, M. G., van der Zanden, B. P., de Borgie, C. A., et al (2005) Cost utility analysis of co-prescribed heroin compared with methadone maintenance treatment in heroin addicts in two randomised trials. BMJ, 330, 12971302.
Farnbacher, G., Basdekis-Josza, R., Krausz, M. (2002) Psychoedukation als Methode in der Drogenhilfe. In Drogenpraxis Drogenrecht Drogenpolitik [Psychoeducation as a method in addiction services. In Practice, Legislation and Policy on Drugs]. (eds Böllinger, L. & Stöver, H.), pp. 386402. Fachhochschulverlag.
Ferri, M., Davoli, M. & Perucci, C. A. (2005) Heroin maintenance for chronic heroin dependents. Cochrane Library, issue 2. Wiley Interscience.
Gossop, M. (1990) The development of a Short Opiate Withdrawal Scale (SOWS). Addictive Behaviours, 15, 487490.
Kokkevi, A. & Hartgers, C. (1995) EuropASI: European adaptation of a multidimensional assessment instrument for drug and alcohol dependence. European Addiction Research, 1, 208210.
Oliva, H., Görgen, W., Schlanstedt, G., et al (2001) Case Management in der Suchtkranken- und Drogenhilfe [Case Management in Addiction Services]. Nomos.
Paterson, S., Lintzeris, N., Mitchell, T. B., et al (2005) Validation of techniques to detect illicit heroin use in patients prescribed pharmaceutical heroin for the management of opioid dependence. Addiction, 100, 18321839.
Perneger, T. V., Giner, F., del Rio, M., et al (1998) Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatments. BMJ, 317, 1318.
Raschke, P., Püschel, K. & Heinemann, A. (2000) Rauschgiftmortalität und Substitutionstherapie in Hamburg (1990–1998) [Narcotics mortality and maintenance treatment in Hamburg (1990–1998)]. Suchttherapie, 1, 4348.
Rathod, N. H., Addenbrooke, W. M. & Rosenbach, A. F. (2005) Heroin dependence in an English town: 33-year follow-up. British Journal of Psychiatry, 187, 421425.
Rehm, J., Gschwend, P., Steffen, T., et al (2001) Feasibility, safety, and efficacy of injectable heroin prescription for refractory opioid addicts: a follow-up study. Lancet, 358, 14171420.
Rook, E., Huitema, A., van den Brink, W., et al (2006) Screening for illicit heroin use in patients in a heroin-assisted treatment program. Journal of Analytical Toxicology, 30, 390394.
Rounsaville, B. J. (1993) Rationale and guidelines for using comparable measures to evaluate substance abusers: an overview. In Diagnsotic Source Book on Drug Abuse Research and Treatment (eds Rounsaville, B. J., Tims, F. M., Horton, A. M., et al), pp. 110. US Department of Health and Human Services.
van den Brink, W., Hendriks, V. M., Blanken, P., et al (2003) Medical prescription of heroin to treatment resistant heroin addicts: two randomised controlled trials. BMJ, 327, 310312.
World Health Organization (1990) Composite International Diagnostic Interview (CIDI). (German version). Wittchen & Semler.
World Health Organization (1993) The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. WHO.
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Heroin-assisted treatment for opioid dependence: Randomised controlled trial

  • Christian Haasen (a1), Uwe Verthein (a1), Peter Degkwitz (a1), Juergen Berger (a2), Michael Krausz (a3) and Dieter Naber (a3)...
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Response to letter �Important findings for heroin treatment but treatment retention not one of them"

Christian Haasen, psychiatrist
07 September 2007

Dr. Al-Adwani raises an important issue in evaluating the outcome of maintenance treatment, namely how to evaluate the retention rate in an unblinded trial. The special incentive for patients randomised into methadone treatment was the option to switch into the heroin group after completing one year of treatment. Considering the fact that retention is considered one of the main outcome measures for maintenance treatment, ourtrial shows that heroin-assisted treatment (HAT) has two advantages, namely that it reaches a higher number of potential patients (% initiatingtreatment) and that the retention rate of those initiating treatment also is significantly higher for HAT (68.3 vs. 56.3%; LogRank=14.1, p<0.001). Therefore, it is incorrect to say that “retention rates wouldpossibly differ insignificantly”: the difference is certainly less, but still significant. ... More

Conflict of interest: None Declared

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Important findings for heroin treatment but treatment retention not one of them

Andrew Al-Adwani, Consultant Psychiatrist
05 July 2007

Haasen et al (2007) report highly significant findings in their trialof heroin plus methadone maintenance. A small problem is that the heroinplus methadone group were, to a large extent, self-selected with only 2.3%failing to initiate treatment in this group versus 28.8% in the methadone only arms. They state that this “limiting effect is minimised” by randomisation and intention to treat (ITT) analysis. ITT makes their already significant findings even more impressive but randomisation is limited by the unavoidable self-selection in a necessarily unblinded trial. The paper goes on to say “retention was higher in the heroin group, with 67.2% completing the 12 month treatment compared with 40% of the methadone group”, but later this is given as 56.3% for the methadone only group when the 28.8% who did not initiate treatment were excluded. The retention rate would rise again if the dropout (“discontinued”) rate was calculated using the same reduced denominator and therefore retention rates would possibly differ insignificantly. Taking this into consideration would also explain the almost equal numbers of discontinued subjects in the two main arms of the trial.

The findings of this aspect of the trial are not surprising and without doubt it would be difficult to devise a control with the reinforcing power of heroin. Injectable methadone, financial incentives or pleasurable activities might approximate a substitute and produce more accurate retention figures. With the high cost of freeze-dried heroin, asused in the UK, adding these incentives might attract funding for a suitably modified study conducted here. Given that high retention rates are today’s centrally defined most desirable outcome in the UK, this sort of study might be even more attractive within these shores.

Christian Haasen, Uwe Verthein, Peter Degkwitz, Juergen Berger, Michael Krausz, and Dieter Naber (2007) Heroin-assisted treatment for opioid dependence: Randomised controlled trial. British Journal of Psychiatry, 191, 55-62.
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