Commentary on Nikoo et al. (2017): The role of research.

Abstract

Opium tincture (OT) is used in Iran because it has two critical advantages—it is cheap, and it is less stigmatized than methadone. Stigma, and the problem of funding stigmatized treatments, is an issue in every country. Might OT be a solution? The evidence is limited, but reviewing it is useful. Nikoo and colleagues 1 report that in Iran there are 64 000 people in treatment with opium tincture (OT), the majority in slow withdrawal programmes. They have weighed the evidence concerning this preparation and found it wanting. They found observational trials of OT in substitution treatment, but no controlled trials. There were two controlled trials of OT in opioid withdrawal, with inconclusive results. Is OT a suitable medication for managing opioid dependence? Cost is one reason why the government of Iran used OT, and in low-income countries lower-cost treatment options are critical. Parsimony might seem a poor basis for choosing a medication without evidence to support it. However, absence of evidence of effectiveness is not evidence of absence of effectiveness. There are grounds for believing that almost any opioid can be used satisfactorily in substitution treatment 2. Well-controlled trials might reveal marginal differences in efficacy, but morphine, codeine and dihydrocodeine, to name a few opioids, have been used in observational studies 3, 4. OST medications do not even need to be long-acting or administered orally, as demonstrated by the effectiveness of injectable diamorphine and hydromorphone 5. Substitute medications work more effectively if they attenuate the effect of injected heroin—which is why high-dose methadone, inducing high opioid tolerance, is more effective than lower doses 6. As expected, a dose effect with OT was noted by Nikoo, with higher doses being more effective. In choosing between opioid drugs for substitution treatment, it might be a case of ‘anything goes’ (as long as given in sufficient dose); but in delivering medication to individuals, it is not the case that any approach is good enough. There are wide variations in how treatment is delivered 7—and better structured and supported treatment is more expensive to deliver and produces more effective outcomes 8. A more relevant question is whether slow opioid withdrawal a suitable treatment. Nikoo and colleagues comment that ‘we still do not have a satisfactory safe and effective treatment for detoxification and maintenance treatment of opioid dependence’; but spontaneous opioid withdrawal is not life-threatening. Most people dependent upon street opioids go through multiple episodes of withdrawal without formal treatment. On safety grounds, there is little need to offer detoxification—on the contrary, there is consistent evidence that post-detoxification heroin users are at increased risk of death 9. We can make withdrawal faster (rapid detoxification), or we can make it slower and less aversive, but however it is conducted relapse rates are high and risks of death post-withdrawal are increased 2, 10. The other major for using OT in Iran was the stigma against methadone. Stigma corrodes all aspects of substitution treatment. Stigma deters people from participating, and families pressure patients to avoid OST 11. People hate being on methadone, and drop out. Stigma against substitution treatment is one reason that professionals offer, and patients choose, detoxification rather than maintenance. The research reviewed by Nikoo and colleagues may permit few conclusions about OT relative to other medications, but it is important, none the less. Research helps to destigmatize treatment. It frames addiction as an empirical problem to be investigated, rather than an ethical problem to be corrected. It focuses not on the daily frustrations of dosing large numbers of people with minimal friction, but on the question of whether there are things we could do more effectively. It identifies end-points against which to evaluate treatment, guiding staff and patients towards realistic objectives and away from magical thinking. These ‘side effects’ of research into addiction are its greatest benefits—more valuable even than the occasional reporting of a vaguely relevant finding. Most of us have given up waiting for the big breakthrough that will cure addiction, but we still value the research enterprise. Research, even negative findings, helps us to think—and to cope with the stigma that bears down upon everyone involved in addiction. J.B. has received speaker's fees from Indivior and consultancy fees from Martindale Pharma.