Podcast: Clonidine, lofexidine, and similar medications for the management of opioid withdrawal

The Cochrane Drugs and Alcohol Group oversees the reviews of interventions to help people with alcohol and other drug problems. In May 2016, their review of the use of alpha two adrenergic agonists for managing opioid withdrawal was updated by Linda Gowing from the University of Adelaide in Australia and her colleagues. Linda describes the latest findings in this podcast.

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John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. The Cochrane Drugs and Alcohol Group oversees the reviews of interventions to help people with alcohol and other drug problems. In May 2016, their review of the use of alpha two adrenergic agonists for managing opioid withdrawal was updated by Linda Gowing from the University of Adelaide in Australia and her colleagues. Linda describes the latest findings in this podcast.

Linda: People who are dependent on opiates such as heroin, oxycontin or morphine, need to undergo withdrawal as a first step to longer-term treatment. Although withdrawal from opioid drugs is not usually life-threatening, uncomfortable symptoms and intense craving make it difficult for most people. Approaches to the management of opioid withdrawal involve either the use of non-opioid medications to reduce the signs and symptoms of withdrawal, or the use of opioid medications to suppress withdrawal, with doses of medications then reduced over a short period of time.
Alpha2-adrenergic agonists are a group of non-opioid drugs that help to reduce the physical signs and symptoms of withdrawal by dampening the sympathetic nervous system response. Examples are clonidine, lofexidine and guanfacine. We found 26 studies that considered the use of alpha2-adrenergic agonists in opioid withdrawal and met our eligibility criteria for the review. Six studies compared an alpha2-adrenergic agonist with placebo, 12 studies used reducing doses of methadone as the comparison; and five directly compared different alpha2-adrenergic agonists.
We found low to moderate evidence that treatment regimes based on clonidine or lofexidine had similar efficacy to those based on reducing doses of methadone over a period of around 10 days. The severity of withdrawal associated with either approach is similar, although the signs and symptoms of withdrawal occur and resolve earlier with adrenergic agonists, and the duration of treatment is significantly longer with reducing doses of methadone. At first, this might be perceived as a negative outcome if completion of withdrawal was the end of addiction, but further, structured treatment is needed for sustained abstinence to be achieved, and so a longer period of managed withdrawal provides greater opportunities for planning aftercare and should be seen as a positive outcome. 
The placebo controlled trials showed that alpha2-adrenergic agonists are more effective than placebo in reducing the severity of withdrawal and supporting the completion of withdrawal treatment. We were not able to make detailed comparison of different alpha2-adrenergic agonists but the available data did suggest that lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine.
There is still a need for more research into the relative efficacy of clonidine, lofexidine and other alpha2-adrenergic agonists. This might be more easily done using descriptive outcome studies rather than controlled clinical trials, and such an approach would provide information on the performance of these medications when used in routine clinical practice. Further investigation of the effect of treatment setting (inpatient or outpatient) is also desirable.

John: If you would like to find more about the existing evidence base for the use of alpha2-adrenergic agonists in the management of opioid withdrawal, and to watch for future updates when further research becomes available, go online to Cochrane Library dot com and search ‘adrenergic agonists for opioid withdrawal’ to find Linda’s full review.

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