Elsevier

The Lancet

Volume 361, Issue 9358, 22 February 2003, Pages 662-668
The Lancet

Articles
1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial

https://doi.org/10.1016/S0140-6736(03)12600-1Get rights and content

Summary

Background

The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence, but there are few long-term and placebo-controlled studies of its effectiveness. We aimed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence.

Methods

40 individuals aged older than 20 years, who met DSM-IV criteria for opiate dependence for at least 1 year, but did not fulfil Swedish legal criteria for methadone maintenance treatment were randomly allocated either to daily buprenorphine (fixed dose 16 mg sublingually for 12 months; supervised daily administration for a least 6 months, possible take-home doses thereafter) or a tapered 6 day regimen of buprenorphine, thereafter followed by placebo. All patients participated in cognitive-behavioural group therapy to prevent relapse, received weekly individual counselling sessions, and submitted thrice weekly supervised urine samples for analysis to detect illicit drug use. Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat.

Findings

1-year retention in treatment was 75% and 0% in the buprenorphine and placebo groups, respectively (p=0·0001; risk ratio 58·7 [95% CI 7·4–467·4]). Urine screens were about 75% negative for illicit opiates, central stimulants, cannabinoids, and benzodiazepines in the patients remaining in treatment.

Interpretation

The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious, and should be added to the treatment options available for individuals who are dependent on heroin.

Introduction

Heroin dependence is a major cause of morbidity and mortality.1 In the absence of effective treatment, Swedish heroin addicts have a mortality rate 20-fold to 50-fold higher than their sex and age matched peers who are not dependent on heroin.2 Abstinence-oriented treatment continues to be the most commonly offered treatment option in Scandinavia and many other parts of the world; however, this approach is not supported by evidence. Beneficial effects of psychosocial support and psychological treatment for heroin dependence have been reported,3, 4 but their efficacy has always been tested in individuals who are in methadone-maintenance programmes. Without parallel agonist treatment, psychosocial interventions have consistently failed to show effectiveness, mainly because of low retention in treatment programmes despite long detoxification periods and intensive psychosocial interventions.5

By contrast, a large amount of published work shows that maintenance treatment with methadone, a long acting full opiate receptor agonist, can greatly increase adherence to treatment, lessen illicit drug use, and reduce mortality.2, 6, 7 On the basis of this evidence, guidelines implying that methadone maintenance treatment should be expanded have been published.1 Nevertheless, many restrictions remain on the use of methadone in Scandinavia, because of unsubstantiated fears of primary methadone addiction and leakage from treatment programmes to uncontrolled street use. However, although the proportion of patients receiving methadone should increase in accordance with published guidelines, a specific threshold for inclusion does seem to be medically warranted.

Buprenorphine might, therefore, be a useful complementary or alternative option to methadone. The partial opiate-receptor agonist profile of this compound is, in theory, attractive, and this drug could be used to suppress heroin craving and, antagonise heroin effects, while having a limited potential for dose escalation and, toxicity. Individual comparative studies of buprenorphine in heroin dependence8, 9, 10, 11, 12, 13 and meta-analyses of these14, 15 show that this compound is efficacious in comparison with other available options, and observational data from France lend support to the notion of reduced toxicity.16 Because it is a partial agonist, buprenorphine could be especially useful for patients who need only a limited degree of agonist action.

Interpretation of results of published studies of the effectiveness of buprenorphine has long been limited by features of trial design. For example, there are only a few placebo-controlled studies that assess the efficacy of buprenorphine (a 14-day17 and a 12-week trial,18) and with the exception of one study in which the outcome of buprenorphine treatment was clearly inferior to 80 mg methadone maintenance,10 follow-up has been limited to 3–6 months. Furthermore, few attempts have been made to benefit from the increased retention in buprenorphine programmes to deliver concurrent evidence based, behaviour-oriented, psychosocial treatment. Although improved retention in treatment and reduced illicit drug use have been associated with buprenorphine, there has been little structured assesment of the effects of this treatment on other difficulties of heroin addiction. From a practical point of view, several studies have used an alcohol solution of buprenorphine, whereas the marketed product is a sublingual tablet.

We aimed to assess the efficacy of a highly structured, integrated treatment package that consisted of buprenorphine in a daily sublingual dose of 16 mg, relapse-prevention group therapy,19, 20 weekly counselling sessions, and thrice weekly urine screens.

Section snippets

Pilot phase

In the pilot phase in September, 1999, we recruited five individuals who were moderately heroin dependent (ie, had a mean addiction severity index [ASI] composite score of 2·5 [SD 1·76, range 1·9–3·8]) to an open-label pilot trial. The 4 men and 1 woman were aged between 27–34 years at the onset of treatment, had fullfilled DSMIV criteria for heroin dependence for at least 1 year, and had had repeated admissions to a chemical-dependence unit in central Stockholm. Procedures during the first 6

Results

Of 441 patients admitted between May 1, 2000, and April 1, 2001, 43 were eligible for the study (figure 1). The most common reasons for ineligibility were that patients qualified, or might have qualified, for methadone treatment and were offered referral to the Stockholm methadone programme, or they had codependence on other substances. Two eligible patients declined to participate, and one decided to attempt abstinence-oriented treatment. The remaining 40 participants were all randomly

Discussion

We have shown that the combination of buprenorphine and intensive psychosocial treatment is safe and highly effective in the treatment of heroin addiction.

Although previous studies have indicated a potentially useful efficacy of buprenorphine for heroin dependence,8, 9, 10, 11, 12, 13, 14, 15, 23 the placebo-controlled design of our trial provides information not otherwise available. The use of a placebo group in the study was ethically complicated in view of known morbidity and mortality

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