Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. Some patients who take pharmaceutical opioids to treat pain become dependent on them and might need to switch to medications such as opioid agonists. In September 2022, an updated Cochrane Review brought together the relevant evidence and, in this podcast, Addiction Psychiatrist Shalini Arunogiri from Monash University and Turning Point in Melbourne talks with lead author, Suzanne Nielsen (or Suzi) from the Monash Addiction Research Centre in Australia.

Shalini: Hello Suzi. Firstly, can you tell us a little about pharmaceutical opioids and how they might be harmful for some people?

Suzi: Hello Shalini. Pharmaceutical opioids are medicines that are commonly used for pain, but they have similar effects in the body to well-known illicit drugs like heroin. In recent years, there have been dramatic increases in pharmaceutical opioid use in some higher income countries and pharmaceutical drugs contribute to a substantial number of fatal overdoses. For example, here in Australia, prescription opioids cause most of the opioid-related deaths.

Shalini: That's worrying, and makes your review of Opioid Agonist Treatment particularly important, so could you tell us about this therapy and why you did the review? 

Suzi: Opioid agonist treatment, also known as opioid maintenance treatment, involves prescribing maintenance doses of an opioid medication to remove the need to take the drug of dependence; in this case, pharmaceutical opioids. Opioid agonist treatments, which include medications like methadone and buprenorphine, are one of the main evidence-based treatments for people who are dependent on illicit opioids and are also commonly used for people who have become dependent on opioid medications for the treatment of pain. This makes it important to assess the evidence for their use for pharmaceutical opioid dependence, given that most of the research into the effectiveness of opioid agonist treatments has come from studies conducted primarily or exclusively with people who are dependent on heroin. We wanted to see what research is available on opioid agonists specifically for the treatment of pharmaceutical opioid dependence and looked for studies of different types of full and partial opioid agonist maintenance treatments, as well as comparisons of opioid agonist maintenance treatment to placebo, detoxification or other psychological treatments that did not involve an agonist maintenance treatment.

Shalini: What types of effects were you looking for and what studies did you find?

Suzi: We were primarily interested in the effect of these treatments on substance use, as well as how well they keep people in treatment. We had also wanted to look at some other outcomes such as pain, quality of life and employment; but there was insufficient evidence for most of these secondary outcomes in the eight randomised trials, involving just over 700 people, that we found. Seven of the eight studies were from the US and the other was from Iran. Four of the studies directly compared different maintenance agonist treatments (methadone and buprenorphine) and four compared maintenance buprenorphine with non-opioid maintenance treatments (detoxification, brief intervention or naltrexone).

Shalini: What about the quality of the evidence and can we trust it?

Suzi: The overall quality was very low to moderate, which means that there is a need for some caution in interpreting it. This is due to the relatively small size of the studies and the use of open label designs, in which participants and researchers knew which medication the person in the study was receiving.

Shalini: Given those cautions, what about the results of trials. What did you find?

Suzi: We found that when comparing methadone with buprenorphine maintenance treatments, methadone may keep more people in treatment than buprenorphine, but this seems to be driven mainly by the findings of one of the four studies. We also found that people on methadone may report less opioid use than people on buprenorphine, although when the participants' urine was tested for opioids, there was no difference between the two medications.
In the comparison of buprenorphine maintenance with other non-opioid treatments such as detoxification, opioid antagonists like naltrexone or psychological treatments, we found that buprenorphine probably keeps more people in treatment and may be better at helping people reduce opioid use.

Shalini: So, what would you say are the implications for practice of your review?

Suzi: Even though here is low‐certainty evidence favouring maintenance methadone over buprenorphine for pharmaceutical opioid dependence on some outcomes, the benefits are small and unstable. It's also important to note that the safety profile of methadone and its restricted availability in some settings, means that other clinician or treatment system factors and patient preference might also be important for informing the choice of pharmacotherapy for an individual patient.
Focusing on buprenorphine maintenance, this seems to have advantages over non-opioid agonist treatment options in terms of keeping people in treatment, and reducing opioid use, and these findings are consistent with the earlier version of our review.

Shalini Thanks Suzi and, finally, if people would like to read your review, how can they find it?

Suzi: Thanks Shalini. If they go online to Cochrane Library dot com and search 'opioid agonist treatment', they'll be given a link to the review at the top of the list.