NDARC Monograph No. 34 (1997)
Executive Summary and Recommendations
Induction onto naltrexone maintenance
The procedure of rapid opioid detoxification using naltrexone is linked to naltrexone maintenance and it is recommended that any measure of effectiveness of rapid detoxification must primarily take account of the long-term outcomes of patients in naltrexone maintenance. Naltrexone maintenance will prove beneficial for some patients wishing to cease opioid use. The objective of any research conducted in this area should be to trial the efficacy, safety and cost-effectiveness of naltrexone maintenance and the ability of different methods of inducting patients onto naltrexone maintenance to achieve long-term abstinence successfully.
Approaches to induction onto naltrexone maintenance
There are a number of methods for commencing naltrexone maintenance, including:
- accelerated induction using naltrexone in conscious patients without sedation/anaesthesia delivered as an in-patient or day-patient and transfer to naltrexone maintenance;
- accelerated induction with anaesthesia using naltrexone and transfer to naltrexone maintenance;
- transfer from heroin/methadone to buprenorphine and then to naltrexone maintenance;
- standard in-patient or out-patient detoxification with clonidine and other medications for symptomatic relief and transfer to naltrexone maintenance.
It is possible that the induction process may influence the outcomes of naltrexone maintenance treatment, and this needs to be investigated. However, anaesthesia may not be required or beneficial, and there is a need to trial nonanaesthesia methods of induction onto naltrexone maintenance. The most parsimonious position at this time is that of Dr Colin Brewer, a long-standing practitioner of anaesthesia-based detoxification, who states that it cannot be claimed that patients having precipitated withdrawal with opioid antagonists show better long-term results than comparable patients who complete conventional inpatient withdrawal programmes (Brewer, 1997b), as there is no evidence to date for or against the claim that anaesthesia improves long-term outcomes. It is recommended that the ability of any procedure inducting patients onto naltrexone to successfully lead to long-term abstinence from opioids be tested carefully.
Planned trials
A number of planned or mooted trials are thought to be important. These include a randomised clinical trial assessing the value of using buprenorphine to transfer stable methadone patients to naltrexone maintenance, a randomised clinical trial of accelerated induction onto naltrexone maintenance treatment, and a randomised clinical trial of anaesthesia assisted accelerated induction onto naltrexone maintenance treatment. As we do not have good knowledge about the effect of antagonists on opiate receptor activity, in any research it will be valuable to examine the functional effect of these medications and their ability to reduce craving and their potential to increase overdose deaths.
Standard of the research
It is recommended that the guidelines for Good Clinical Research Practice (GCRP) in Australia or a similar standard for the research should be adopted in randomised trials, provided that adequate funding is provided. These guidelines have the objective of safeguarding the interests of subjects, investigators, sponsors and society in ensuring that only adequately planned and conducted clinical studies are performed. Unless the entire procedure, including the analysis of data, is adequately conducted, there is a risk of failure and hence an unethical waste of human and financial resources.
Combining data from different trials in Australia
There are likely to be a number of trials mounted of induction onto naltrexone maintenance. Research results from different trials should be combined to allow quasi-experimental comparisons. The other advantage of pooling data is that the individual trials are unlikely to be able to address the question of which patients fare best with each procedure, and a large sample of patients undergoing different procedures will allow the development of an understanding of patient-treatment matching. This will assist to guide policy and practice. The core data set to be collected, and the most appropriate mechanism to support the combination of results from the different research projects, requires further consideration to ensure that the different research groups agree on the data to be collected, its analysis and dissemination.
Serious adverse events associated with induction onto naltrexone maintenance
Deaths associated with rapid induction onto naltrexone maintenance under anaesthesia are relatively unlikely in well supported intensive care units or similarly supported medical wards. There is a lack of clear information concerning symptoms during and soon after accelerated detoxification prior to the induction onto naltrexone. There are sufficient comments in the literature about patients suffering under accelerated detoxification procedures using naltrexone, for extreme caution to be exercised in any trial. One area of concern regarding naltrexone maintenance treatment is that it (like other procedures which lead to abstinence from opioids) may increase the risk of overdose for patients who cease naltrexone treatment and relapse to either occasional or regular opioid use. Another concern is the potential for induction onto naltrexone to destabilise patients who were functioning well in methadone maintenance therapy. It is important to inform patients of the potential risks of destabilisation, and to provide safeguards for these patients, including ensuring entry into methadone maintenance therapy should the patient fare poorly.
Media scrutiny and rational policy development
The level of media attention given to rapid detoxification using naltrexone to date, and the subsequent public perception that this procedure provides a "cure" for opioid dependence remains an issue. Any study of induction onto naltrexone maintenance will receive substantial media attention, and reports of even small groups of "successfully" treated patients could result in considerable pressure for the procedure to be implemented more widely. Any pre-post evaluation of rapid opioid detoxification runs the risk that methods of induction onto naltrexone maintenance will not be subject to the standards of evidence required of other interventions for serious disorders in Australia. Methods to deal with this problem need to be considered.
Key outstanding issues
There are three remaining issues:
- An analysis of current and proposed research projects should be undertaken to ensure that there are no substantial gaps in assessment of the different mechanisms of induction onto naltrexone maintenance.
- A mechanism for centralised, coordinated, national analysis of the outcomes of the various trials needs to be agreed and established in a fashion that protects each groups rights and responsibilities with regard to the data they collect.
- A strategy for managing the media attention and public perceptions regarding unique effectiveness of rapid opioid detoxification should be developed and nationally agreed.