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Laura Murphy,1 Karen Ng,2 Pearl Isaac,3 Jaris Swidrovich,4 Maria Zhang,3,5 Beth A Sproule3,5 1Department of Pharmacy, University Health Network, Toronto, ON, Canada; 2Toronto Academic Pain Medicine Institute, Toronto, ON, Canada; 3Pharmacy Department, Centre for Addiction and Mental Health, Toronto, ON, Canada; 4College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada; 5Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, CanadaCorrespondence: Beth A SprouleCentre for Addiction and Mental Health (CAMH), 1025 Queen Street West, Toronto, ON, M6J 1H4, CanadaTel +1-416-535-8501 x35601Fax +1-416-583-1277Email beth.sproule@camh.caAbstract: Pharmacists across the healthcare continuum are well positioned to collaborate with patients to effectively manage their chronic pain. Evidence supports positive outcomes when pharmacists undertake these roles; however, there are barriers preventing uptake across the profession. This paper aims to expand awareness of the breadth of these roles, including pharmaceutical care provision, interprofessional collaboration, pain and medication education, support for patients in self-management and acceptance of responsibility to be culturally responsive and decrease stigma. Pharmacists are accessible healthcare professionals and can improve the care of patients with chronic pain.Keywords: chronic pain, pharmacist, patient-centered care, stigma

The purposes of this study were to examine predictors of benzodiazepine use among methadone maintenance treatment patients, to determine whether baseline benzodiazepine use influenced ongoing use during methadone maintenance treatment, and to assess the effect of ongoing benzodiazepine use on treatment outcomes (i.e., opioid and cocaine use and treatment retention). A retrospective chart review of 172 methadone maintenance treatment patients (mean age = 34.6 years; standard deviation = 8.5 years; 64% male) from January 1997 to December 1999 was conducted. At baseline, 29% were 'non-users' (past year) of benzodiazepine, 36% were 'occasional users,' and 35% were 'regular/problem users.' Regular/problem users were more likely to have started opioid use with prescription opioids, experienced more overdoses, and reported psychiatric comorbidity. Being female, more years of opioid use, and a history of psychiatric treatment were significant predictors of baseline benzodiazepine use. Ongoing benzodiazepine users were more likely to have opioid-positive and cocaine-positive urine screens during methadone maintenance treatment. Only ongoing cocaine use was negatively related to retention. Benzodiazepine use by methadone maintenance treatment patients is associated with a more complex clinical picture and may negatively influence treatment outcomes. [ABSTRACT FROM AUTHOR]

The evidence is reviewed for effective serum lithium concentrations for the acute and prophylactic treatment of mania and depression in patients with bipolar disorder. The efficacy of lithium in the treatment of acute manic episodes has been recognised for several decades, primarily using concentrations in the range of 0.8 to 2 mmol/L. The number of patients responding increases as the serum lithium concentration increases, although individual patients may respond at lower concentrations (<0.8 mmol/L). Lithium doses and serum concentrations similar to those used to treat acute mania have been studied in bipolar depression, with no evaluation of a relationship between concentration and clinical response. Several prospective controlled trials have evaluated this relationship in the prophylactic treatment of bipolar disorder. Maintaining higher serum lithium concentrations (0.8 to 1 mmol/L) improves the likelihood of good effect in prophylactic treatment, although individual patients may do well on lower concentrations. Despite the paucity of evidence to specifically support the efficacy of lithium at lower serum lithium concentrations in the elderly, lower target ranges (0.5 to 0.8 mmol/L) are commonly recommended due to an increased sensitivity to adverse effects, particularly neurotoxicity. The serum lithium concentrations recommended in adults have been applied to children; however, this has not been studied. Overall, the evidence suggests a relationship between serum lithium concentration and therapeutic effect, although the exact nature of this relationship is not clear. For example, it is not known why some people respond to lower concentrations and others do not. There are many factors that influence studies trying to elucidate this relationship. Many of these factors are related to the interpretation of the serum lithium concentration. In summary, patients have an increased chance of responding to lithium if 12-hour serum lithium concentrations at steady state are above 0.8 mmol/L. Many patients will respond to lower concentrations (0.4 to 0.7 mmol/L), but we are unable to identify these patients a priori. The relationship between serum lithium concentrations and adverse effects is also very important in determining appropriate target lithium concentrations. The current best advice is to individualise the target serum lithium concentrations based on efficacy and tolerability and to optimise the interpretation of these concentrations by ensuring within-patient consistency with respect to dosage schedule, lithium preparation and the timing of blood sampling. [ABSTRACT FROM AUTHOR]

Laura Murphy,1,2 Karen WK Ng,1 Victoria CH Su,3 Sarah Woodworth-Giroux,4 Todd S Levy,1 Beth A Sproule,2,5 Andrea D Furlan1,6 1University Health Network, Toronto, ON, Canada; 2Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; 3St Paul's Hospital, Lower Mainland Pharmacy Services, Vancouver, BC, Canada; 4Windsor Regional Hospital, Windsor, ON, Canada; 5Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; 6Institute for Work and Health, Toronto, ON, Canada Abstract: This paper provides an overview of research, guidelines, and clinical considerations for the use of medications for chronic pain in the management of patients with an alcohol use disorder. A review of the literature identified randomized controlled trials, epidemiological cohort studies, consensus guidelines, and one systematic review and meta-analysis. Where gaps in the literature existed, clinical experience of the authors is included. Use of nonopioid medications should be given priority and may offer a more favorable risk profile as well as benefits beyond pain management, such as improvement in anxiety, depression, or insomnia. Pregabalin and gabapentin have additional benefits to decrease alcohol cravings or time to relapse after a period of abstinence from alcohol. Drug interactions between selected analgesics and alcohol, disulfiram, or naltrexone require careful consideration. Keywords: chronic pain, alcohol use disorder, opioids

Abstract Background There is a significant public health burden associated with substance use in Canada. The early detection and/or treatment of risky substance use has the potential to dramatically improve outcomes for those who experience harms from the non-medical use of psychoactive substances, particularly adolescents whose brains are still undergoing development. The Screening, Brief Intervention, and Referral to Treatment model is a comprehensive, integrated approach for the delivery of early intervention and treatment services for individuals experiencing substance use-related harms, as well as those who are at risk of experiencing such harm. Methods This article describes the protocol for a systematic review of the effectiveness of brief interventions as part of the Screening, Brief Intervention, and Referral to Treatment model for reducing the non-medical use of psychoactive substances. Studies will be selected in which brief interventions target non-medical psychoactive substance use (excluding alcohol, nicotine, or caffeine) among those 12 years and older who are opportunistically screened and deemed at risk of harms related to psychoactive substance use. We will include one-on-one verbal interventions and exclude non-verbal brief interventions (for example, the provision of information such as a pamphlet or online interventions) and group interventions. Primary, secondary and adverse outcomes of interest are prespecified. Randomized controlled trials will be included; non-randomized controlled trials, controlled before-after studies and interrupted time series designs will be considered in the absence of randomized controlled trials. We will search several bibliographic databases (for example, MEDLINE, EMBASE, CINAHL, PsycINFO, CORK) and search sources for grey literature. We will meta-analyze studies where possible. We will conduct subgroup analyses, if possible, according to drug class and intervention setting. Discussion This review will provide evidence on the effectiveness of brief interventions as part of the Screening, Brief Intervention, and Referral to Treatment protocol aimed at the non-medical use of psychoactive substances and may provide guidance as to where future research might be most beneficial.

Objectives: The purpose of this study was to examine sex-stratified independent predictors of patient-initiated discharge from an inpatient withdrawal management service and to determine whether those predictors differed by sex., Methods: This study compared people who had self-initiated versus planned discharges and used sex-stratified generalized estimating equations models to identify independent predictors of patient-initiated discharge. Predictors examined included age, ethnicity, substance of concern, tobacco use, mental health comorbidities, day of discharge, referral source, children, and social assistance funds., Results: Among females, there were 722 discharges, 116 of which were patient initiated. Among females, increasing age was associated with lower odds of patient-initiated discharge ( OR = 0.97, 95% CI [0.95, 0.98]). Racialized females were nearly 2 times more likely to experience patient-initiated discharge compared with White females ( OR = 1.8, 95% CI [1.09, 3.00]). Compared with weekdays, weekends were associated with over 4 times the odds of patient-initiated discharge ( OR = 4.77, 95% CI [2.66, 8.56]). Having one or more mental health comorbidities was associated with lower odds of patient-initiated discharge compared with having no mental health comorbidities ( OR = 0.51, 95% CI [0.32, 0.82]). Among males, there were 1,244 discharges, 185 of which were patient initiated. Among males, increasing age was associated with decreased odds of patient-initiated discharge ( OR = 0.97, 95% CI [0.95, 0.98]). Compared with weekdays, weekends were associated with nearly 15 times the odds of patient-initiated discharge ( OR = 14.9, 95% CI [9.11, 24.3])., Conclusions: Males and females have shared and unique predictors of patient-initiated discharge. Future studies should continue to examine the influence of sex and gender on engagement with addictions care., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2024 International Nurses Society on Addictions.)

Background: The COVID-19 pandemic has accelerated and amplified the use of virtual research methods. While online research has several advantages, it also provides greater opportunity for individuals to misrepresent their identities to fraudulently participate in research for financial gain. Participant deception and fraud have become a growing concern for virtual research. Reports of deception and preventative strategies have been discussed within online quantitative research, particularly survey studies. Though, there is a dearth of literature surrounding these issues pertaining to qualitative studies, particularly within substance use research. Results: In this commentary, we detail an unforeseen case study of several individuals who appeared to deliberately misrepresent their identities and information during participation in a virtual synchronous qualitative substance use study. Through our experiences, we offer strategies to detect and prevent participant deception and fraud, as well as challenges to consider when implementing these approaches. Conclusions: Without general awareness and protective measures, the integrity of virtual research methods remains vulnerable to inaccuracy. As online research continues to expand, it is essential to proactively design innovative solutions to safeguard future studies against increasingly sophisticated deception and fraud.

Background: Uptake and retention for opioid agonist treatment (OAT) remains low. Novel extended-release formulations may improve OAT accessibility by reducing the frequency of healthcare visits. Our aim was to examine uptake, characteristics, treatment patterns and retention of individuals initiating extended-release subcutaneous buprenorphine (BUP-ER), a monthly injectable OAT., Methods: We conducted a population-based cohort study among adults aged 18+ initiated on BUP-ER between February 3, 2020 and March 31, 2022 in Ontario, Canada. Using administrative health data, we defined continuous BUP-ER use based on repeat injections within a 56-day period and used Kaplan-Meier curves to estimate time on treatment. Among new BUP-ER recipients, we described individual and prescriber characteristics, healthcare utilization and treatment patterns., Results: 2366 individuals initiated BUP-ER. The median time to BUP-ER discontinuation was 183 days (interquartile range: 66-428 days) and 52.0% of individuals were co-prescribed buprenorphine/naloxone at least once throughout the period of BUP-ER receipt. Among individuals who initiated on a dose of 300mg BUP-ER and had three or more injections, 18.8% continued to receive only 300mg doses (N=276 of 1470). Furthermore, 28.6% of those whose dose was reduced to 100mg (N=341 of 1194) had a subsequent dose increase to 300mg., Conclusions: On average, people initiating BUP-ER discontinue within the first 6 months of treatment. While BUP-ER is likely providing an important OAT option, the high occurrence of discontinuation, supplementation with buprenorphine/naloxone, and frequent dose increases suggest inadequacy of current dosing recommendations among a proportion of individuals., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Rationale: Methamphetamine use and related harms have risen at alarming rates. While several psychosocial and pharmacologic interventions have been described in the literature, there is uncertainty regarding the best approach for the management of methamphetamine use disorder (MUD) and problematic methamphetamine use (PMU). We conducted a scoping review of recent systematic reviews (SR), clinical practice guidelines (CPG), and primary controlled studies of psychosocial and pharmacologic treatments for MUD/PMU., Methods: Guided by an a priori protocol, electronic database search updates (e.g., MEDLINE, Embase) were performed in February 2022. Screening was performed following a two-stage process, leveraging artificial intelligence to increase efficiency of title and abstract screening. Studies involving individuals who use methamphetamine, including key subgroups (e.g. those with mental health comorbidities; adolescents/youths; gay, bisexual, and other men who have sex with men) were sought. We examined evidence related to methamphetamine use, relapse, use of other substances, risk behaviors, mental health, harms, and retention. Figures, tables and descriptive synthesis were used to present findings from the identified literature., Results: We identified 2 SRs, one CPG, and 54 primary studies reported in 69 publications that met our eligibility criteria. Amongst SRs, one concluded that psychostimulants had no effect on methamphetamine abstinence or treatment retention while the other reported no effect of topiramate on cravings. The CPG strongly recommended psychosocial interventions as well as self-help and family support groups for post-acute management of methamphetamine-related disorders. Amongst primary studies, many interventions were assessed by only single studies; contingency management was the therapy most commonly associated with evidence of potential effectiveness, while bupropion and modafinil were analogously the most common pharmacologic interventions. Nearly all interventions showed signs of potential benefit on at least one methamphetamine-related outcome measure., Discussion: This scoping review provides an overview of available interventions for the treatment of MUD/PMU. As most interventions were reported by a single study, the effectiveness of available interventions remains uncertain. Primary studies with longer durations of treatment and follow-up, larger sample sizes, and of special populations are required for conclusive recommendations of best approaches for the treatment of MUD/PMU., Competing Interests: BH has previously received honoraria from Eversana Inc for provision of methodologic advice related to the conduct of systematic reviews. All other authors have no conflicts to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Hersi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction The Routine Opioid Outcome Monitoring (ROOM) Tool was developed for use in community pharmacies in Australia. It facilitates pharmacists' screening and brief interventions regarding an individual's opioid use for chronic pain. At our academic teaching hospital, the ROOM Tool was adapted to incorporate a communication tool that includes a pharmacist's assessment and recommendations for primary care providers. This modified ROOM Tool was implemented as part of usual care in our outpatient pharmacies; however, the value to primary care providers is unknown. Aim The aim of this study was to determine primary care provider perspectives on the modified ROOM Tool. Methods Focus groups were conducted with primary care providers from an Academic Family Health Team. The focus group encompassed topics related to the positive and negative aspects of the modified ROOM Tool in supporting the care of patients using opioids for chronic pain. Qualitative content analysis of transcripts was performed to identify themes. Results Three focus groups were conducted with a total of six participants. Four themes emerged: (i) Facilitators to using the tool, (ii) Barriers to using the tool, (iii) Recommendations for improvement, (iv) Impact of the tool on patient care and safety. Discussion The ROOM Tool paired with the communication tool supports collaboration between pharmacists and primary care providers. The communication tool standardises the approach for communicating the pharmacist's assessment and recommendations. Recommendations to refine this modified ROOM Tool may increase its utility to primary care providers and enhance the impact on patient care and safety.

Background: Slow-release oral morphine (SROM) is used to manage pain, and as opioid agonist treatment (OAT). Between 2017 and 2021 in Canada, several drug shortages occurred for Kadian© (SROM-24). The purpose of this study was to evaluate the impact of these shortages on people's ability to remain on this medication., Methods: We conducted a retrospective population-based time series analysis of SROM-24 dispensed between January 1, 2014, and December 31, 2021, in Ontario, Canada. Using interventional autoregressive integrated moving average models (ARIMA) models, we evaluated the association between SROM-24 drug shortages and treatment discontinuation. Analyses were also stratified by the SROM-24 indication (pain or OAT)., Results: We identified 22,479 SROM-24 recipients, of which one-third (33.9%) were aged 65 or above and just over half (51.9%) were female. In our primary analysis of monthly SROM-24 discontinuation, we observed a significant sustained monthly increase following the shortages in November 2019 (+0.29%/month; 95% CI: 0.16%, 0.43%; p < .001) with significant sudden, temporary changes following the shortages in March 2020 (+2.00%; 95% CI: 0.95%, 3.05%; p < .001), July 2021 (+3.53%; 95% CI: 2.20%, 4.86%; p < .001), and August 2021 (+4.98%; 95% CI: 3.49%, 6.47%; p < .001). Similar results were observed in our stratified analyses, with sustained high rates of discontinuation among people accessing SROM-24 as OAT., Conclusions: The SROM-24 shortages resulted in significant treatment disruptions across all recipients. These findings have important implications for those with few treatment alternatives, including people using SROM-24 as OAT who are at risk of adverse outcomes following treatment disruptions., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Co-use of alcohol and cannabis is associated with increased frequency and intensity of use and related problems. This study examined acute effects of alcohol and cannabis on mood, subjective experience, cognition, and psychomotor performance. Twenty-eight healthy cannabis users aged 19-29 years with recent history of binge drinking completed this within-subjects, double-blind, double-dummy, placebo-controlled, randomized clinical trial. Participants received: placebo alcohol and placebo cannabis (<0.1% THC); alcohol (target breath alcohol content [BrAC] 80 mg/dL) and placebo cannabis; placebo alcohol and active cannabis (12.5% THC); and active alcohol and cannabis over four sessions. Profile of Mood States (POMS), Addiction Research Centre Inventory (ARCI), verbal free recall (VFR), Digit Symbol Substitution Test (DSST), Continuous Performance Test (CPT), and grooved pegboard (GPB) task were administered before and approximately 75 min after drinking alcohol (1 h after smoking cannabis ad libitum). Significant effects of condition were found for the POMS (Tension-Anxiety, Confusion) and ARCI (MBG, LSD, PCAG, Euphoria, Sedation), predominantly with greater increases emerging after cannabis or alcohol-cannabis combined relative to placebo. Significant effects were found for VFR (immediate total and delayed recall, percent retained), DSST (trials attempted, trials correct, reaction time), and GPB (non-dominant hand) predominantly with greater declines in performance after alcohol and alcohol-cannabis combined relative to placebo and/or cannabis. Cannabis appeared to affect mood and subjective experience, with minimal impact on cognitive performance. Alcohol appeared to impair cognitive and psychomotor performance, with minimal impact on mood and subjective experience. Acute effects of alcohol and cannabis combined were additive at most., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: To characterize comparative risks and benefits of methadone versus buprenorphine/naloxone in a contemporary cohort where the unregulated drug supply is dominated by fentanyl., Design, Setting and Participants: Population-based propensity-score matched cohort study conducted in Ontario, Canada among people aged 18+ initiating opioid agonist therapy (OAT) for an opioid use disorder between October 2016 and December 2018 (n = 18 880)., Intervention: Initiation of methadone versus buprenorphine/naloxone., Measurements: The primary outcome was opioid overdose (fatal and non-fatal) while on treatment, with secondary outcomes including opioid overdose (first 30 days of treatment), treatment discontinuation, health-care interactions related to treatment of opioid use disorder, receiving a weekly supply of take-home doses and opioid overdose within 30 days of treatment discontinuation. Outcomes were assessed over 1 year., Findings: Overall, 7517 people initiating buprenorphine were matched to an equal number of methadone-treated individuals. Risk of opioid overdose while on treatment [hazard ratio (HR) = 0.50; 95% confidence interval (CI) = 0.37-0.68] or within the first 30 days of treatment (HR = 0.51, 95% CI = 0.31-0.85) was lower among buprenorphine recipients compared to methadone recipients. In secondary analyses, people initiating buprenorphine had a higher risk of treatment discontinuation within the first year (median time to discontinuation 104 versus 265 days, HR = 1.43, 95% CI = 1.37-1.49), had lower rates of health-care interactions for OUD (186.4 versus 254.3 per person-year; rate ratio = 0.73; 95% CI = 0.72-0.75), and a higher rate of receiving weekly take-home doses (HR = 2.33; 95% CI = 2.20-2.46). Overdose rates in the period following OAT discontinuation were higher than those observed while on treatment, but did not differ significantly by OAT type., Conclusions: Although treatment retention is higher among methadone recipients, overdose risk is also elevated compared to buprenorphine recipients. These findings demonstrate the benefits of any OAT on avoidance of overdose, particularly following treatment discontinuation and with the increasingly unpredictable drug supply in North America., (© 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: The opioid epidemic is an international public health concern. Pharmacists are in a strategic position to promote and implement effective opioid stewardship due to both their central role on health care teams and frequent interaction with patients. Despite this integral role, pharmacists do not have harmonized scopes of practice in opioid stewardship., Objectives: This scoping review was conducted to identify and critically review the role of pharmacists in opioid stewardship and identify future areas of study., Methods: The scoping review was conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases were searched for original, peer-reviewed research; PubMed (MEDLINE), Ovid Embase, Ovid International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo., Results: In 92% of the included studies (n = 77), opioid stewardship interventions led by either a pharmacist or in an interdisciplinary team resulted in improvements in at least one outcome measure, with education and medication therapy adjustments being the most predominant activities. Other areas supported by evidence include community stakeholder education, policy and guideline setting, and risk assessment., Conclusion: This scoping review provides valuable insight into the various roles pharmacists can have in opioid stewardship. The findings from this review identified opioid stewardship activities that can make significant contributions towards reducing the impact of the opioid crisis. This review informs future research and has the potential to influence pharmacy practice on a national and international scale., (Copyright © 2021 Elsevier Inc. All rights reserved.)