Eugenia Socias

Background: North America is facing an opioid epidemic primarily attributable to potent synthetic opioids. There has been a marked increase in methamphetamine/amphetamine use and related harms among people who use opioids. However, little is known about this population and their treatment-related outcomes. The aim of this thesis was to characterize the population of people with prescription-type opioid use disorder (POUD) who use methamphetamine/amphetamine, and to determine the effects of methamphetamine/amphetamine use and opioid agonist therapy (OAT) on treatment-related outcomes. Methods: Secondary analysis of a pan-Canadian pragmatic trial comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care among POUD. Multivariable logistic regression analyses were used to determine correlates of baseline methamphetamine/amphetamine use (measured by urine drug test [UDT] and self-report). Cox proportional hazard models were used to evaluate the impact of baseline methamphetamine/amphetamine use on OAT discontinuation. Generalized linear mixed models were used to examine the comparative effectiveness of buprenorphine/naloxone versus methadone on methamphetamine/amphetamine use. Results: Among the 272 randomized participants, 185 (68.0%) were using methamphetamine/amphetamine at baseline. Fentanyl use in the last 30 days (adjusted odds ratio [AOR] = 11.59, 95% confidence interval [CI] = 5.90 – 23.68] was independently and positively associated with baseline methamphetamine/amphetamine use. Among participants that initiated treatment (n = 210), 130 (61.9%) were using methamphetamine/amphetamine at baseline. Baseline methamphetamine/amphetamine use was associated with shorter median times in assigned OAT (36 versus 168 days, adjusted hazard ratio [aHR] = 2.07, CI = 1.22 – 3.49) and any OAT (41 days versus 168 days, aHR = 1.83, CI = 1.05 – 3.17). Neither treatment type nor time in treatment were significantly associated with the odds of methamphetamine/amphetamine use (p > 0.05). Conclusions: In this sample of people with POUD, methamphetamine/amphetamine use was associated with markers of complex and severe OUD, including fentanyl exposure, and increased risk of OAT discontinuation. Methadone and buprenorphine/naloxone did not have an impact on methamphetamine/amphetamine use over the 24-week intervention. These findings suggest the need for targeted interventions, including development of evidence-based treatments for methamphetamine/amphetamine use within specific subgroups, to prevent future overdoses and optimize treatment outcomes in this population.

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Background: Canada is currently facing an overdose epidemic primarily attributed to prescription and synthetic opioids. Previous work has revealed that individuals with a history of non-fatal overdose (NFO) are at a higher risk of mortality, but little is known about treatment outcomes among this population. The aim of this thesis was to characterize opioid agonist treatment (OAT) seeking individuals with prescription-type opioid use disorder (POUD) and a history of NFO, as well as their treatment outcomes. Methods: Data were drawn from OPTIMA, a multi-site, 24-week, pragmatic, randomized control trial evaluating the relative effectiveness of buprenorphine/naloxone and methadone models of care for adults with POUD. Multivariable logistic regression was used to determine correlates of NFO and to explore treatment retention among participants with a history of NFO. Analysis of covariance (ANCOVA) was used to examine the mean difference in opioid use between treatment arms. Finally, descriptive statistics were produced to determine the prevalence of overdose during treatment and investigate patterns of opioid use before and after overdose.Results: Among the 272 randomized participants, 159 (58%) had a lifetime history of NFO. Homelessness, receiving income assistance and positive urine drug screens (UDS) for fentanyl and methamphetamine were all independently associated with a history of NFO. Among participants with a history of NFO, retention was 17% for the buprenorphine/naloxone group and 18% for the methadone group and was not statistically different between the treatment arms (p = 0.54). Across the study period, there was an 11.9% adjusted mean difference in opioid-free UDS, favouring the buprenorphine/naloxone arm (95% CI= 3.5 to 20.3; p=0.0057). A total of 24 overdoses were reported during the study period (6 participants randomized to buprenorphine/naloxone; 12 randomized to methadone). All participants that initiated treatment continued to use opioids after overdose. Conclusions: Findings from this research indicate that a considerable proportion of OAT-seeking individuals have a history of NFO. Low retention rates and high opioid use in treatment highlight the importance of an individualized, multidimensional approach to treatment for this population. Timely initiation of low-barrier treatment and interventions to address socio-structural barriers could potentially mitigate future overdose and improve treatment outcomes.

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