Impact of Depressive Symptom Severity on Buprenorphine/Naloxone and Methadone Outcomes in People With Prescription-Type Opioid Use Disorder: Results From a Pragmatic Randomized Controlled Trial.

OBJECTIVE: To evaluate the impact of depressive symptom severity on opioid use and treatment retention in individuals with prescription-type opioid use disorder (POUD). METHOD: We analyzed data from a multi-centric, pragmatic, open-label, randomized controlled trial comparing buprenorphine/naloxone to methadone models of care in 272 individuals with POUD. Opioid use was self-reported every two weeks for 24 weeks using the Timeline Followback. Depressive symptom severity was self-reported with the Beck Depression Inventory at baseline, week 12 and week 24. RESULTS: Baseline depressive symptom severity was not associated with opioid use nor treatment retention. At week 12, moderate depressive symptoms were associated with greater opioid use while mild to severe depressive symptoms were associated with lowered treatment retention. At week 24, moderate depressive symptoms were associated with greater opioid use. CONCLUSIONS: Ongoing depressive symptoms lead to poorer outcomes in POUD. Clinicians are encouraged to use integrative approaches to optimize treatment outcomes. This study was registered in ClinicalTrials.gov (NCT03033732) on January 27th, 2017, prior to participants enrollment.

Associations Between Buprenorphine\Naloxone and Methadone Treatment and non-Opioid Substance Use in Prescription-Type Opioid Use Disorder: Secondary Analyses From the OPTIMA Study: Associations entre le traitement avec la buprénorphine/naloxone et avec la méthadone et l'utilisation de substances non opioïdes dans le trouble lié à l'usage d'opioïdes de type sur ordonnance : analyses secondaires de l'étude OPTIMA.

OBJECTIVES: There is limited evidence on how opioid agonist treatment (OAT) may affect psychoactive non-opioid substance use in prescription-type opioid use disorder (POUD) and whether this effect might explain OAT outcomes. We aimed to assess the effect of methadone on non-opioid substance use compared to buprenorphine/naloxone (BUP/NX), to explore whether non-opioid substance use is associated with opioid use and retention in treatment, and to test non-opioid use as a moderator of associations between methadone with retention in OAT and opioid use compared to BUP/NX. METHODS: This is a secondary analysis of data from the OPTIMA trial, an open-label, pragmatic, parallel, two-arm, pan-Canadian, multicentre, randomized-controlled trial to compare standard methadone model of care and flexible take-home dosing BUP/NX for POUD treatment. We studied the effect of methadone and BUP/NX on non-opioid substance use evaluated by urine drug screen (UDS) and by classes of non-opioid substances (i.e., tetrahydrocannabinol [THC], benzodiazepines, stimulants) (weeks 2-24) using adjusted generalized estimation equation (GEE). We studied the association between non-opioid substance-positive UDS and opioid-positive UDS and retention in treatment, using adjusted GEE and logistic regressions. RESULTS: Overall, methadone was not associated with non-opioid substance-positive UDS compared to BUP/NX (OR: 0.78; 95%CI, 0.41 to 1.48). When non-opioid substances were studied separately, methadone was associated with lower odds of benzodiazepine-positive UDS (OR: 0.63; 95% CI: 0.40 to 0.98) and THC-positive UDS (OR: 0.47; 95% CI: 0.28 to 0.77), but not with different odds of stimulant-positive UDS (OR: 1.29; 95% CI: 0.78 to 2.16) compared to BUP/NX. Substance-positive UDS, overall and separate classes, were not associated with opioid-positive UDS or retention in treatment. CONCLUSION: Methadone did not show a significant effect on overall non-opioid substance use in POUD compared to BUP/NX treatment but was associated with lower odds of benzodiazepine and THC use in particular. Non-opioid substance use did not predict OAT outcomes. Further research is needed to ascertain whether specific patterns of polysubstance use (quantity and frequency) may affect treatment outcomes.

Differential effect of cannabis use on opioid agonist treatment outcomes: Exploratory analyses from the OPTIMA study.

INTRODUCTION: Conflictual evidence exists regarding the effects of cannabis use on the outcomes of opioid agonist therapy (OAT). In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a trial comparing flexible buprenorphine/naloxone (BUP/NX) take-home dosing model to witnessed ingestion of methadone. METHODS: We analyzed data from a multi-centric, pragmatic, 24-week, open label, randomized controlled trial in individuals with prescription-type opioid use disorder (n = 272), randomly assigned to BUP/NX (n = 138) or methadone (n = 134). The study measured last week cannabis and opioid use via timeline-follow back, recorded at baseline and every two weeks during the study. Craving symptoms were measured using the Brief Substance Craving Scale at baseline, and weeks 2, 6, 10, 14, 18 and 22. The study measured opioid withdrawal symptoms via Clinical Opiate Withdrawal Scale at treatment initiation and weeks 2, 4, and 6. RESULTS: The mean maximum dose taken during the study was 17.3 mg/day (range = 0.5-32 mg/day) for BUP/NX group and 67.7 mg/day (range = 10-170 mg/day) in the methadone group. Repeated measures generalized linear mixed models demonstrated that cannabis use in the last week (mean of 2.3 days) was not significantly associated with last week opioid use (aß ± standard error (SE) = -0.06 ± 0.04; p = 0.15), craving (aß ± SE = -0.05 ± 0.08, p = 0.49), or withdrawal symptoms (aß ± SE = 0.09 ± 0.1, p = 0.36). Bayes factor (BF) for each of the tested models supported the null hypothesis (BF < 0.3). CONCLUSIONS: The current study did not demonstrate a statistically significant effect of cannabis use on outcomes of interest in the context of a pragmatic randomized-controlled trial. These findings replicated previous results reporting no effect of cannabis use on opioid-related outcomes.

Effects of Buprenorphine/Naloxone and Methadone on Depressive Symptoms in People with Prescription Opioid Use Disorder: A Pragmatic Randomised Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effectiveness of flexible take-home dosing of buprenorphine/naloxone (BUP/NX) and methadone standard model of care in reducing depressive symptoms in people with prescription-type opioid use disorder (POUD). This trial also evaluated whether improvements in depressive symptoms were mediated by opioid use. METHODS: Analyzed data came from the OPTIMA study (clinicaltrials.gov identifier: NCT03033732), a pragmatic randomised controlled trial comparing flexible take-home dosing of BUP/NX and methadone standard model of care for reducing opioid use in people with POUD. A total of 272 participants were recruited in four Canadian provinces. Participants were randomised 1:1 to BUP/NX or methadone. After treatment induction, past two-week opioid use was measured using the Timeline Followback every two weeks for a total of 24 weeks. Depressive symptoms were measured with the Beck Depression Inventory at baseline, weeks 12 and 24. RESULTS: Both BUP/NX and methadone significantly reduced depressive symptoms at week 12 (aß ± SE = -3.167 ± 1.233; P < 0.001) and week 24 (aß ± SE = -7.280 ± 1.285; P < 0.001), with no interaction between type of treatment and time (P = 0.284). Improvements in depressive symptoms were only partially mediated by a reduction in opioid use (proportion mediated = 36.8%; 95% confidence interval = -1.158 to -0.070; P = 0.015). CONCLUSIONS: BUP/NX and methadone showed similar effectiveness in decreasing comorbid depressive symptoms in people with POUD. This effect was partially explained by a reduction in opioid use. As both treatments seem equally effective, clinicians are encouraged to tailor the selection of OAT to patients' needs and characteristics.

Buprenorphine/naloxone and methadone effectiveness for reducing craving in individuals with prescription opioid use disorder: Exploratory results from an open-label, pragmatic randomized controlled trial.

BACKGROUND: Craving reduction is an important target in the treatment of prescription-type opioid use disorder (POUD). In this exploratory analysis, we compared the effectiveness of BUP/NX flexible model of care relative to methadone for craving reduction in individuals with POUD. METHODS: We analyzed data from a multicentric, pragmatic, 24-week open-label randomized controlled trial conducted in participants with POUD (N = 272) who were randomly assigned to BUP/NX model of care with flexible take-home dosing (n = 138) or the standard model of care with closely supervised methadone (n = 134). Treatments were prescribed and administered according to local guidelines, in diverse clinical settings. Craving was measured using the Brief Substance Craving Scale at baseline, week 2, 6, 10, 14, 18 and 22. RESULTS: Cravings decreased in both treatment groups over 22 weeks (BUP/NX adjusted mean difference = -5.52, 95% CI = -6.91 to -4.13; methadone adjusted mean difference = -3.95, 95% CI = -5.28 to -2.63; p < 0.001), and were overall lower in the BUP/NX group (adjusted mean = 4.04, 95% CI = 3.43-4.64) than the methadone group (adjusted mean = 5.13, 95% CI = 4.51-5.74; p < 0.001). The time by treatment group interaction (favoring BUP/NX) was statistically significant at week 2 (adjusted mean difference = -1.58, 95% CI = -3.13 to -0.03; p = 0.041). CONCLUSIONS: Compared to the standard methadone model of care, flexible take-home dosing of BUP/NX was associated with lower craving in individuals with POUD. These findings can contribute to guiding shared decision-making regarding OAT treatment in this population.

Commentary on the impact of the COVID-19 pandemic on opioid use disorder treatment among Indigenous communities in the United States and Canada.

This commentary focuses on how some Indigenous communities in the United States (U.S.) and Canada are addressing the opioid epidemic within the context of the COVID-19 pandemic, from the perspective of the co-authors as researchers, clinicians, and pharmacists working within or among Indigenous communities in three eastern Canadian provinces and two western U.S. states. The pandemic has likely exacerbated opioid use problems among Indigenous communities, especially for individuals with acute distress or comorbid mental illness, or who are in need of withdrawal management or residential services. In response to the pandemic, we discuss first how greater prescription flexibility has facilitated and even increased access to medications for opioid use disorder. Second, we describe how Indigenous-serving clinics have expanded telemedicine services, albeit not without some challenges. Third, we note challenges with restricted participation in traditional Indigenous healing practices that can be helpful for addiction recovery. Fourth, we mention providers' worries about the pandemic's impact on their patients' mental health and safety. We argue that certain treatment transformations may be helpful even after the pandemic is over, through enhancing access to community-grounded treatment, decreasing stigma, and promoting patient self-efficacy.

[Opioid use disorder in patients with chronic non-cancer pain]. / Les troubles liés à l'utilisation des opioïdes prescrits médicalement.

Epidemiology Canada now has the second highest number of opioid prescriptions per capita in the world. The rate of prescriptions has increased over the last decade, most notably in adults over 55 years of age. A recognition of the importance of treating pain has influenced this increase, but higher rates of opioid prescribing have produced undesirable outcomes including the misuse of medication as well as an increased number of deaths and emergency department visits attributable to opioids. Diverse psychiatric disorders, such as major depression, now also occur in 40% of those with an opioid use disorder (OUD). Neuroscience We now understand that addictive behaviors are caused by both environmental and genetic factors. Although OUD has historically been perceived as a weakness of character, it is now clear that it is a chronic disease, which results from a complex interaction between a substance, such as opioid, environmental factors, and an individual's genotype. Unfortunately, this evidence has yet to be successfully translated into clinical practice and most physicians are unable to diagnose and manage OUD patients appropriately.Clinical guidelines Many clinical guidelines for the management of chronic, non-cancer pain are available. All guidelines identify the need to assess the patient appropriately and screen for factors associated with misuse before prescribing opioids. Guidelines generally acknowledge that patients should not be denied appropriate pain management, but that some patients will require close supervision and frequent follow-up to prevent the misuse of prescription opioids.