History of Treatment Access and Drug Use among Participants in a Trial Testing Injectable Opioids under Supervision for Long-Term Heroin Injectors

Background: For opioid-dependent patients not benefitting from conventional treatments (i.e., oral methadone), evidence suggests that supervised injectable medications are effective. The present study aims to describe participants’ baseline characteristics in a study comparing injectable diacetylmorphine and hydromorphone and factors independently associated with prior access to methadone at high doses. Methods: SALOME (Study to Assess Longer-term Opioid Medication Effectiveness) is a phase III, randomized, double blind controlled trial comparing injectable diacetylmorphine and hydromorphone in 202 chronic, opioid-dependent, current injection opioid users in Vancouver who had at least one prior episode of opioid maintenance treatment (OMT). Measures included questionnaires and drug dispensation records. In addition to descriptive statistics, multivariable logistic regression was used to determine characteristics associated with reaching a stable weekly average methadone dose of 100 mgs daily or more during a methadone treatment episode. Results: Participants had a mean of fifteen years of illicit opioid use, several OMT attempts, medical problems, criminal justice histories, unstable housing, daily use of illicit opioids and regular use of cocaine. Multivariable analysis showed that individual characteristics, such as separation from biological parents, prior prescription of opioids for pain and other medical conditions, and preferred methadone dose were independently associated with prior methadone episodes that reached 100 mgs. Conclusions: These data emphasize that study participants were in need of alternative treatments at the time of enrolment and fit the profile of patients to whom supervised injectable treatment should be offered. Adding specific dose and duration requirements with respect to prior OMT might exclude individuals who would benefit significantly from injectable treatment. Central Oviedo-Joekes et al. (2015) Email: J Addict Med Ther 3(1): 1015 (2015) 2/11 in these trials were in their late thirties, had used heroin for fifteen years or more, had two to four prior MMT attempts, and presented with poor physical and psychological health and many psychosocial problems such as unstable housing, illegal activities, repeated incarceration and unemployment [9,14,15]. Although these studies reached very similar target populations, eligibility criteria regarding prior and current methadone treatment differed significantly by setting. For example, currently being on MMT was an inclusion criterion in the trials conducted in the Netherlands and the United Kingdom [8,16], while for the Canadian trial it was an exclusion criterion [12]. For the other trials, it was neither [10,11,15,17]. A previous MMT attempt was an inclusion criterion for the trials in the Netherlands [8], Spain [11], Canada [12] and Belgium [15], and some of them further specified that participants received at least 60 milligrams (mg) of methadone for at least one month. It has been proposed that treatment with injectable DAM should be offered as a second line option, after the patient has attempted maintenance treatment with oral methadone (or buprenorphine) and if not currently fully benefiting from this or other treatment [13]. Current guidelines state that most MMT patients will achieve stability on daily maintenance doses of 60 mg and above [18], and higher doses have been encouraged when patients cannot reach abstinence or minimal use of illicit opioids [16,19,20]. As this was the case for the target population of the DAM trials (i.e., continuing regular use of illicit opioids), the average MMT dose of the methadone arm in most of these trials was around 100 mg [9-12]. Some have argued that injectable medications such as DAM, should be restricted only to those who have previously experienced extended exposure to methadone doses of 100 mg or higher [21]. Even though there is some evidence suggesting that higher methadone doses may be clinically beneficial for people still using illicit opioids, a high dose is not necessarily the appropriate dose [19,22] and flexible individualized doses are recommended for MMT [18]. Roux et al. [23] recently showed that perceived methadone dose inadequacy (too low or too high), and not MMT dose itself, was independently associated with long-term nonadherence. Together with the fact that the DAM trials reached similar populations despite differences in MMT entry criterion suggests that prior detailed MMT requisites might not be enough or adequate as a clinical indicator of treatment with injectables. Moreover, recent evidence showed that DAM was more effective than MMT for those without a prior history of MMT [24]. This opens the possibility that offering injectable maintenance treatment only to individuals who have a history of MMT might further neglect many heroin-dependent individuals who have always remained outside of treatment. Injectable medications are an effective approach to attracting such people into treatment, who may later transition into MMT [25]. SALOME (Study to Assess Longer-term Opioid Medication Effectiveness) is an ongoing randomized double-blind controlled trial testing whether injectable hydromorphone is as effective as diacetlymorphine for the treatment of long-term opioiddependent individuals who are not benefitting sufficiently from available treatments. The present study aims first, to describe participants’ characteristics at study entry; and second, to determine factors independently associated with prior methadone episodes in which participants received high doses. These results could provide clinicians and policy makers with evidence to decide whether high doses of prior MMT should be required to be eligible for treatment with injectable medications.