Regular article Controlled trial of prescribed heroin in the treatment of opioid addiction Joan Carles March, (Ph.D.) a , Eugenia Oviedo-Joekes, (Ph.D.) a, 4 , Emilio Perea-Milla, (Ph.D.) b , Francisco Carrasco, (M.D.) c , the PEPSA team 1 a Andalusian School of Public Health, Granada 18080, Spain b Costa del Sol Hospital, Marbella 29600, Spain c Andalusian Health Care Service, Almeria 04071, Spain Received 16 November 2005; received in revised form 18 April 2006; accepted 18 April 2006 Abstract Aim: This study aimed to assess the efficacy of the prescription of intravenous diacetylmorphine (DAM) versus oral methadone with medical and psychosocial support, with a view of improving physical and mental health as well as social integration among socially excluded, opioid-dependent individuals for whom standard treatments have failed. Design: This study used an open, randomized controlled trial. Setting: This study took place in Granada, Spain. Participants: Sixty-two opioid-dependent participants were randomized, 31 in each treatment group, and 50 of them were analyzed. The participants were recruited directly from the streets, through peer outreach, in well-known meeting places for drug-addicted individuals. Interventions: Participants in the experimental group received injected DAM, twice a day, plus oral methadone, once a day, for 9 months. The control group received only oral methadone, once a day. The two groups received an equivalent opioid dosage. The average DAM dosage was 274.5 mg/day (range: 15–600 mg), and an average methadone dosage was 42.6 mg/day (range: 18–124 mg). The daily methadone dosage in the control group was 105 mg/day (range: 40–180 mg). Comprehensive clinical, psychological, social, and legal support was given to both groups. Measurements: The following were measured in this study: general health, quality of life, drug-addiction-related problems, nonmedical use of heroin, risk behavior for HIV and HCV, and psychological, family, and social status. Findings: Both groups improved with respect to the total domain assessed. Those in the experimental group showed greater improvement in terms of physical health (the improvement was 2.5 times higher; p = .034) and risk behavior for HIV infection (the improvement was 1.6 times higher; p = .012). In addition, this group decreased its street heroin use from 25 days/month to 8 days/month as seen on the Addiction Severity Index ( p = .020), as well as the number of days free from drug-related problems (the improvement was 2.1 times higher; p = .004) or involvement in crime (from 11 days/month to b1 day/month; p = .096 between groups). Conclusions: These findings support the hypothesis that, under the same conditions, DAM could be safely delivered, in our context. Also, in physical health, HIV risk behavior, street heroin use, and days involved in crime, DAM plus methadone 0740-5472/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.jsat.2006.04.007 The study protocol was developed in 2001 and was funded by the Drug Commission, Council for Equality and Social Welfare, Andalusian Government. Recruitment began in February 2003, and the study was finished in December 2004. The guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish. The study obtained ethical approval from the Ethical Committee of Clinical Research (Virgen de las Nieves University Hospital) and was conducted according to Good Clinical Practice guidelines. Patients gave written consent for participation. The EudraCT number 2005-002896-33 has been issued for Protocol Code Number PEPSA-CAS-CD 2001, the experimental drug prescription program in Andalusia (PEPSA), a comparative, randomized, and open study on the difference between intravenous diacetylmorphine and the prescription of oral methadone—both treatments administered as individualized procedures following appropriate protocols and with medical and psychosocial support—through a 9-month period for the treatment of opiate-dependent patients who have failed under previous treatments. 4 Corresponding author. E-mail address: eugenia.oviedojoekes.easp@juntadeandalucia.es (E. Oviedo-Joekes). 1 The PEPSA team is composed of Andre ´s Estrada Moreno, Jose ´ Manuel Rodrı ´guez, Francisco Gonza ´lez-Sa ´iz, Rosario Ballesta, Salvador Rodrı ´guez, Manuel Romero, and Miguel Marset. Journal of Substance Abuse Treatment 31 (2006) 203 – 211