Feasibility and outcome of substitution treatment of heroin-dependent patients in specialized substitution centers and primary care facilities in Germany: a naturalistic study in 2694 patients.

BACKGROUND: In many countries, buprenorphine and methadone are licensed for the maintenance treatment (MT) of opioid dependence. Despite many short-term studies, little is known about the long-term (12-month) effects of these treatments in different settings, i.e. primary care-based (PMC) and specialized substitution centers (SSCs). OBJECTIVES: To describe over a period of 12 months: (1) mortality, retention and abstinence rates; (2) changes in concomitant drug use, somatic and mental health; and (3) to explore differences between different types of provider settings. METHODS: 12-Month prospective-longitudinal naturalistic study with four waves of assessment in a prevalence sample of N=2694 maintenance patients, recruited from a nationally representative sample of N=223 substitution physicians. RESULTS: The 12-month retention rate was 75%; the mortality rate 1.1%. 4.1% of patients became "abstinent" during follow-up. 7% were referred to drug-free addiction treatment. Concomitant drug use decreased and somatic health status improved. No significant improvements were observed for mental health and quality of life. When controlling for initial severity, small PMC settings revealed better retention, abstinence and concomitant drug use rates. CONCLUSION: The study underlines the overall 12-month effectiveness of various forms of agonist MT. Findings reveal relatively high retention rates, low mortality rates, and improvements in most 12-month outcome domains, except for mental health and quality of life. PMC settings appear to be a good additional option to improve access to MTs.

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

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.

One-year mortality rates of patients receiving methadone and buprenorphine maintenance therapy: a nationally representative cohort study in 2694 patients.

Mortality rates in drug-dependent patients in substitution treatment remain a matter of debate. Although several retrospective toxicological or forensic postmortem studies on this issue have been conducted, few prospective studies have addressed this problem. In a nationally representative sample of 2694 opioid dependent patients in substitution treatment either with methadone or buprenorphine at baseline were monitored over a 12-month period (response rate, 91%). A total number of 1629 (60.4%) were still in treatment after 12 months. The overall mortality rate was 1.04%. In total, 28 patients of the initial sample deceased within the 1-year follow-up period. Eleven (0.4%) of these deaths are due to a fatal intoxication. Three patients (0.1%) died of human immunodeficiency virus/acquired immunodeficiency syndrome, and 3 (0.1%) committed suicide. Thirteen of these patients (4 with overdose/polyintoxication) were not in substitution treatment at the time of death. Other reasons included accidents and deaths due to other medical conditions. Only in one case the reason could not be ascertained. The mortality rate was similar in methadone as compared with buprenorphine patients. Taking into account the high comorbidity of opioid dependent patients and the severity of dependence, the mortality rate of approximately 1% confirms that maintenance treatment could be regarded as a fairly safe treatment.