A randomised trial of the cost effectiveness of buprenorphine as an alternative to methadone maintenance treatment for heroin dependence in a primary care setting.

BACKGROUND AND AIM: Buprenorphine offers an alternative to methadone in the treatment of heroin dependence, and has the advantage of allowing alternate-day dosing. This study is the first to examine the cost effectiveness of buprenorphine as maintenance treatment for heroin dependence in a primary care setting using economic and clinical data collected within a randomised trial. STUDY DESIGN AND METHODS: The study was a randomised, open-label, 12-month trial of 139 heroin-dependent patients in a community setting receiving individualised treatment regimens of buprenorphine or methadone. Those who were currently on a methadone program (n = 57; continuing therapy subgroup) were analysed separately from new treatment recipients (n = 82; initial therapy subgroup). The study took a broad societal perspective and included health, crime and personal costs. Data on resource use and outcomes were a combination of clinical records and self report at interview. The main outcomes were incremental cost per additional day free of heroin use and per QALY. An analysis of uncertainty calculated the likelihood of net benefits for a range of acceptable money values of outcomes. All costs were in 1999 Australian dollars (DollarA). RESULTS: The estimated mean number of heroin-free days did not differ significantly between those randomised to methadone (225 [95% CI 91, 266]), or buprenorphine (222 [95% CI 194, 250]) over the year of the trial. Buprenorphine was associated with an average 0.03 greater QALYs over 52 weeks (not significant). The total cost was DollarA 17,736 (95% CI -DollarA 2981, DollarA 38,364) with methadone and DollarA 11,916 (95% CI DollarA 7697, DollarA 16,135) with buprenorphine; costs excluding crime were DollarA 4513 (95% CI DollarA 3495, DollarA 5531) and DollarA 5651 (95% CI DollarA 4202, DollarA 7100). With additional heroin-free days as the outcome, and crime costs included buprenorphine has a lower cost but less heroin-free days. If crime costs are excluded buprenorphine has a higher cost and worse outcome than methadone. With additional QALYs as the outcome, the cost effectiveness of buprenorphine is DollarA 39,404 if crime is excluded, but buprenorphine is dominant if crime is included. CONCLUSIONS: The trial found no significant differences in costs or outcomes between methadone and buprenorphine maintenance in this particular setting. Although some of the results suggest that methadone may have a cost advantage, it is difficult to infer from the trial data that offering buprenorphine as an alternative would have a significant effect on total costs or outcomes. The point estimates of costs and outcomes suggest that buprenorphine may have an advantage in those initiating therapy. The confidence intervals were wide, however, and the likelihood of net benefits from substituting one treatment for another was close to 50%.

Reducing drug-related harm: Australia leads the way.

Harm-reduction approaches are more easily embedded in policy when drugs are legally regulated.

A randomized trial comparing levo-alpha acetylmethadol with methadone maintenance for patients in primary care settings in Australia.

AIMS: The present study aimed to compare the efficacy of levo-alpha-acetylmethadol (LAAM) and methadone, as measured by retention in treatment and heroin use, in a randomized trial conducted under naturalistic conditions. SETTING: This study is the first randomized trial comparing LAAM with methadone in the primary care setting. Participants were recruited through 29 medical practitioners working in specialist and generalist settings in Australia. PARTICIPANTS: Existing methadone maintenance patients, aged 18 years and over and able to give informed consent, were randomized to receive either LAAM or methadone. A total of 93 patients participated. INTERVENTION: After being trained in the use of LAAM, existing methadone prescribers were then able to determine an individually tailored treatment regimen for each patient. The trial was an open-label study. Methadone and LAAM dosing was supervised through local community pharmacies. Participation in ancillary services (e.g. counselling) was optional for all patients. The treatment period for the trial was 12 months. MEASUREMENTS: Baseline, 3-, 6- and 12-month interviews were conducted. Outcome measures were retention in treatment, self-reported heroin use and serious adverse events. FINDINGS: There were no significant differences between LAAM and methadone on retention in treatment, nor heroin use. There was a trend for LAAM patients to have lower heroin use than methadone patients. Of the seven serious adverse events in the LAAM group, three were not drug-related. There were two dosing errors. CONCLUSIONS: This study demonstrates (a) the efficacy of LAAM as a treatment for heroin dependence, and (b) the capacity for LAAM to be effectively delivered in primary care settings by trained general practitioners and pharmacists. The next challenge is to resolve outstanding safety concerns with LAAM.

Cessation of methadone maintenance treatment using buprenorphine: transfer from methadone to buprenorphine and subsequent buprenorphine reductions.

BACKGROUND: Buprenorphine is used in the treatment of opioid dependence. Due to its pharmacology, the transfer from methadone to buprenorphine may precipitate withdrawal symptoms. METHODS: Methadone maintained patients with clinical indicators of stability who were seeking withdrawal from methadone were recruited from three Australian states. Patients on methadone doses between 30 and 40 mg were randomised to transfer to buprenorphine by a fixed dose (transfer at 30 mg methadone) or by a variable dose induction (transfer when 'uncomfortable'). A third group of patients with methadone doses less than 30 mg were transferred to buprenorphine at their entry methadone dose. Fifty-one patients were inducted onto buprenorphine using the same dosing protocol with the first dose of 4 mg buprenorphine. Following stabilisation on buprenorphine, patients gradually reduced the buprenorphine dose to 0 mg. Withdrawal severity and drug use was monitored. RESULTS: There were no significant difference between the transfer at 30 mg and transfer when 'uncomfortable' dosing protocols in severity of withdrawal on transfer from methadone to buprenorphine. Those on doses less than 30 mg reported significantly less withdrawal discomfort at transfer. All but one patient stabilised on buprenorphine. Thirty-eight of the 51 patients inducted onto buprenorphine reached 0 mg. CONCLUSIONS: Transfer from methadone to buprenorphine can safely occur from doses of around 30 mg of methadone. Buprenorphine dose reductions were well tolerated. Thirty-one percent of patients were not using heroin or methadone at 1-month follow-up.

Naltrexone in the treatment of heroin dependence: relationship with depression and risk of overdose.

OBJECTIVE: This article examines the use of naltrexone in the treatment of heroin dependence. The relationship between naltrexone and depression as well as risk of overdose is examined. METHOD: The existing literature is reviewed along with recent interim data from clinical trials underway in Victoria. RESULTS: Naltrexone is a recent addition to treatment for heroin dependence in Australia. The relationship between depression and naltrexone has been examined in previous literature. Underlying rates of depression in heroin users are high and treatment may resolve or exacerbate depression. Research to date demonstrates that the addition of naltrexone does not necessarily increase depression in patients. The risk of non-fatal heroin overdose is significantly elevated after naltrexone treatment as a result of reduced tolerance. Data from clinical trials underway in Victoria demonstrate a significantly elevated rate of non-fatal overdose in naltrexone patients compared to those in substitution maintenance treatment. The mortality rate subsequent to naltrexone treatment appears to be equivalent to or greater than that for untreated heroin users. Further research is required. CONCLUSIONS: Clinicians need to carefully monitor depression in patients, and warn patients of the risks of reduced tolerance to opiates following naltrexone treatment. Agonist treatments such as methadone, LAAM and buprenorphine carry much less risk of overdose.