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Medical prescription of heroin to treatment resistant heroin addicts: two randomised controlled trials

BMJ 2003; 327 doi: (Published 07 August 2003) Cite this as: BMJ 2003;327:310

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  1. Wim van den Brink, professor (w.vandenbrink{at},
  2. Vincent M Hendriks, senior researcher3,
  3. Peter Blanken, researcher1,
  4. Maarten W J Koeter, assistant professor2,
  5. Barbara J van Zwieten, delegate to CPMP4,
  6. Jan M van Ree, professor5
  1. 1Central Committee on the Treatment of Heroin Addicts (CCBH), Stratenum, Universiteitsweg 100, 3584 CG Utrecht, Netherlands
  2. 2Amsterdam Institute for Addiction Research, Tafelbergweg 25, 1105 BC Amsterdam, Netherlands
  3. 3Parnassia Addiction Research Centre, PO Box 2505 AA The Hague, Netherlands
  4. 4Netherlands Medicines Evaluation Board, Kalvermarkt 53, The Hague, Netherlands
  5. 5Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, Netherlands
  1. Correspondence to: W van den Brink
  • Accepted 23 May 2003


Objective To determine whether supervised medical prescription of heroin can successfully treat addicts who do not sufficiently benefit from methadone maintenance treatment.

Design Two open label randomised controlled trials.

Setting Methadone maintenance programmes in six cities in the Netherlands.

Participants 549 heroin addicts.

Interventions Inhalable heroin (n = 375) or injectable heroin (n = 174) prescribed over 12 months. Heroin (maximum 1000 mg per day) plus methadone (maximum 150 mg per day) compared with methadone alone (maximum 150 mg per day). Psychosocial treatment was offered throughout.

Main outcome measures Dichotomous, multidomain response index, including validated indicators of physical health, mental status, and social functioning.

Results Adherence was excellent with 12 month outcome data available for 94% of the randomised participants. With intention to treat analysis, 12 month treatment with heroin plus methadone was significantly more effective than treatment with methadone alone in the trial of inhalable heroin (response rate 49.7% v 26.9%; difference 22.8%, 95% confidence interval 11.0% to 34.6%) and in the trial of injectable heroin (55.5% v 31.2%; difference 24.3%, 9.6% to 39.0%). Discontinuation of the coprescribed heroin resulted in a rapid deterioration in 82% (94/115) of those who responded to the coprescribed heroin. The incidence of serious adverse events was similar across treatment conditions.

Conclusions Supervised coprescription of heroin is feasible, more effective, and probably as safe as methadone alone in reducing the many physical, mental, and social problems of treatment resistant heroin addicts.


  • Contributors All authors were responsible for analysis and interpretation, revising the manuscript, and final approval of the paper. WvdB and VMH were also responsible for concept and design and the first draft. BJvZ and JMvR were also responsible for concept and design. WvdB is guarantor.

  • Funding The study was commissioned and financially supported by the Netherlands Ministry of Health, Welfare and Sports. The guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish.

  • Conflict of interest None declared.

  • Ethical approval The study was approved by the Central Committee on Medical Ethics (KEMO) and conducted according to ICH/EU Good Clinical Practice guidelines.21 All participants provided written informed consent

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