BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. METHODS: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. RESULTS: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. CONCLUSIONS: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.
BACKGROUND: The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials' outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades. METHODS: Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials. RESULTS: Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52-226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1-26). CONCLUSIONS: Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings. TRIAL REGISTRATION: PROSPERO CRD42013006507. Registered on November 25, 2013.
Narcotic Antagonists , Opiate Substitution Treatment , Opioid-Related Disorders , Randomized Controlled Trials as Topic , Humans , Analgesics, Opioid/therapeutic use , Analgesics, Opioid/adverse effects , Data Interpretation, Statistical , Narcotic Antagonists/therapeutic use , Narcotic Antagonists/adverse effects , Opiate Substitution Treatment/methods , Opioid-Related Disorders/drug therapy , Research Design , Treatment Outcome
Many patients with major depressive disorder (MDD) try multiple antidepressants before finding one that works well and is tolerable. Pharmacogenomic (PGx) testing was developed to facilitate more efficacious prescribing. This technology has not been robustly implemented clinically. Patient perspectives are critical to policy decisions, but the views of patients with MDD about the use of PGx testing to guide antidepressant prescribing have not been extensively examined, particularly in publicly funded healthcare systems. The purpose of this qualitative description study was to produce actionable patient perspectives evidence to inform future technology assessment of PGx testing. We conducted semi-structured interviews with 21 adults with MDD for which antidepressants were indicated in Ontario, Canada, and used the Ontario Decision Determinants Framework to conduct an unconstrained deductive content analysis. Patients expressed views about the overall clinical benefit of PGx testing in depression care, preferences for deployment of testing, perspectives on ethical considerations, opinions about equity and patient care, and beliefs regarding the feasibility of adopting PGx testing into the healthcare system. They also worried about the possibility of conflicts of interest between PGx test manufacturers and pharmaceutical companies. This study provides policymakers with patient priorities to facilitate the development of patient-centred policies. It highlights that formal adoption of PGx testing into the healthcare system requires a focus on equity of access and health outcomes.
BACKGROUND: Findings from randomised controlled trials (RCTs) are synthesised through meta-analyses, which inform evidence-based decision-making. When key details regarding trial outcomes are not fully reported, knowledge synthesis and uptake of findings into clinical practice are impeded. AIMS: Our study assessed reporting of primary outcomes in RCTs for older adults with major depressive disorder (MDD). METHOD: Trials published between 2011 and 2021, which assessed any intervention for adults aged ≥65 years with a MDD diagnosis, and that specified a single primary outcome were considered for inclusion in our study. Outcome reporting assessment was conducted independently and in duplicate with a 58-item checklist, used in developing the CONSORT-Outcomes statement, and information in each RCT was scored as 'fully reported', 'partially reported' or 'not reported', as applicable. RESULTS: Thirty-one of 49 RCTs reported one primary outcome and were included in our study. Most trials (71%) did not fully report over half of the 58 checklist items. Items pertaining to outcome analyses and interpretation were fully reported by 65% or more of trials. Items reported less frequently included: outcome measurement instrument properties (varied from 3 to 30%) and justification of the criteria used to define clinically meaningful change (23%). CONCLUSIONS: There is variability in how geriatric depression RCTs report primary outcomes, with omission of details regarding measurement, selection, justification and definition of clinically meaningful change. Outcome reporting deficiencies may hinder replicability and synthesis efforts that inform clinical guidelines and decision-making. The CONSORT-Outcomes guideline should be used when reporting geriatric depression RCTs.
Opioid use disorder continues to be a health concern with a high rate of opioid related deaths occurring worldwide. Medication Assisted Treatments (MAT) have been shown to reduce opioid withdrawal, cravings and opioid use, however variability exists in individual's treatment outcomes. Sex-specific differences have been reported in opioid use patterns, polysubstance use and health and social functioning. Candidate gene studies investigating methadone dose as an outcome have identified several candidate genes and only five genome-wide associations studies have been conducted for MAT outcomes. This study aimed to identify genetic variants associated with MAT outcomes through genome-wide association study (GWAS) and test the association between genetic variants previously associated with methadone dose through a polygenic risk score (PRS). Study outcomes include: continued opioid use, relapse, methadone dose and opioid overdose. No genome-wide significance SNPs or sex-specific results were identified. The PRS identified statistically significant results (p < 0.05) for the outcome of methadone dose (R2 = 3.45 × 10-3). No other PRS was statistically significant. This study provides evidence for association between a PRS and methadone dose. More research on the PRS to increase the variance explained is needed before it can be used as a tool to help identify a suitable methadone dose within this population.
Analgesics, Opioid , Opioid-Related Disorders , Male , Female , Humans , Analgesics, Opioid/therapeutic use , Genome-Wide Association Study , Opiate Substitution Treatment , Methadone/therapeutic use , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/genetics , Opioid-Related Disorders/rehabilitation
OBJECTIVE: Co-occurring mental health and substance use disorders (concurrent disorders) lead to significant morbidity in children and youth. Programs for integrated treatment of concurrent disorders have been developed; however, there exists little guidance outlining their structure and activities. Our objective was to synthesize available information on outpatient child and youth concurrent disorders programs and produce a comprehensive framework detailing the components of such programs. METHODS: We used a four-stage critical interpretive synthesis design: (1) systematic review of published and grey literature, (2) data abstraction to identify program components and purposive sampling to fill identified gaps, (3) organization of components into a structured framework, (4) feedback from programs. We employed an iterative process by which programs reviewed data abstraction and framework development and provided feedback. RESULTS: Through systematic review (yielding 1,408 records total and 7 records eligible for inclusion) and outreach strategies (yielding an additional 7 eligible records), we identified 11 programs (4 American, 7 Canadian) and 2 theoretical models from which data could be abstracted. Program activities were categorized into 12 overarching constructs that make up the components of the framework: accessibility, engagement, family involvement, integrated assessment, psychotherapy for patients, psychotherapy for families, medication management, health promotion, case management, vocational support, recreation and social support, and transition services. Program components are informed by the philosophical orientation of the program and models of care. This framework considers health system factors, clinical service factors, program development, and community partnership that impact program structure and activities. Multidisciplinary teams provide care and include addiction medicine, psychiatry, psychology, nursing, social work, occupational therapy, recreation therapy, peer support, and program evaluation. CONCLUSION: We developed a comprehensive framework describing components of child and youth outpatient concurrent disorders programs. This framework may assist programs currently operating, and those in development, to reflect on their structure and activities.
Along with the rising burden of peripheral artery disease (PAD), mental health concerns are increasingly being recognized as a comorbidity to address in the chronic disease management of symptomatic PAD. Apart from a high prevalence of comorbid mental health conditions, the role of pain and changing health behaviors and the broader impacts of illness and adaptation to living with PAD require specialized behavioral health expertise. This scientific statement builds a case that this expertise should be integrated within the multidisciplinary PAD team. Furthermore, areas such as cognitive dysfunction and palliative care are highlighted as needing psychological interventions. Although much of the evidence of the efficacy of psychological and psychotropic interventions has been extrapolated from other cardiovascular populations, evidence for the role of psychological interventions for behavior change, for example, uptake of exercise regimens, is increasingly being accrued within PAD. Areas for behavioral health needs and interactions with PAD treatment are discussed, including the use of opioids, depression management, anxiety and stress reduction interventions, the use of benzodiazepines and antidepressants, smoking cessation, rehabilitation trajectories after amputation, and the role of cognitive decline for PAD treatment and outcomes. A case summary highlights the stigma around mental health and vascular disease and the fragmentation of care. This scientific statement provides remarks for building a road map for integrated behavioral PAD care and potential solutions to overcome these barriers. Instrumental to reaching these changes are interprofessional advocacy efforts and initiatives that help break down the stigma around mental health and promote evidence-based collaborative, nonhierarchical, and multidisciplinary PAD care.
Mental Health , Peripheral Arterial Disease , Humans , Risk Factors , American Heart Association , Peripheral Arterial Disease/epidemiology , Comorbidity
AIM: To determine whether the coronavirus disease 2019 (COVID-19) pandemic was associated with a change in psychiatric symptoms in people with preexisting obsessive-compulsive, eating, anxiety, and mood disorders compared to their prepandemic levels. METHODS: We searched MEDLINE, CINAHL, PsycINFO, and Embase from inception until February 16, 2022. Studies were included if they reported prepandemic and during-pandemic psychiatric symptoms, using validated scales, in people with preexisting mood, anxiety, eating, or obsessive-compulsive disorders. Two reviewers independently screened studies, extracted data, and assessed evidence certainty. Random-effects meta-analyses were conducted. Effect sizes were reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: Eighteen studies from 10 countries were included. Of the 4465 included participants, 68% were female and the average age was 43 years. Mood and obsessive-compulsive disorders were the most studied disorders. During-pandemic psychiatric measurements were usually collected during nationwide lockdown. Obsessive-compulsive symptoms worsened among people with obsessive-compulsive and related disorders, with a moderate effect size (N = 474 [six studies], SMD = -0.45 [95% CI, -0.82 to -0.08], I2 = 83%; very low certainty). We found a small association between the COVID-19 pandemic and reduced anxiety symptoms in people with mood, anxiety, obsessive-compulsive, and eating disorders (N = 3738 [six studies], SMD = 0.11 [95% CI, 0.02-0.19], I2 = 63%; very low certainty). No change in loneliness, depressive, or problematic eating symptoms was found. CONCLUSION: People with obsessive-compulsive and related disorders may benefit from additional monitoring during the COVID-19 pandemic and possibly future pandemics. Other psychiatric symptoms were stable in people with the specific disorders studied. Overall, evidence certainty was very low.
COVID-19 , Obsessive-Compulsive Disorder , Female , Humans , Adult , Male , Pandemics , COVID-19/epidemiology , Mood Disorders/epidemiology , Communicable Disease Control , Anxiety/epidemiology , Obsessive-Compulsive Disorder/epidemiology
BACKGROUND: Individuals with an Opioid Use Disorder (OUD) have increased rates of cannabis use in comparison to the general population. Research on the short- and long-term impacts of cannabis use in OUD patients has been inconclusive. A genetic component may contribute to cannabis cravings. AIMS: Identify genetic variants associated with cannabis use through Genome-wide Association Study (GWAS) methods and investigate a Polygenic Risk Score (PRS). In addition, we aim to identify any sex differences in effect size for genetic variants reaching or nearing genome-wide significance in the GWAS. METHODS: The study outcomes of interest were: regular cannabis use (yes/no) (n = 2616), heaviness of cannabis use (n = 1293) and cannabis cravings (n = 836). Logistic and linear regressions were preformed, respectively, to test the association between genetic variants and each outcome, regular cannabis use and heaviness of cannabis use. GWAS summary statistics from a recent large meta-GWAS investigating cannabis use disorder were used to conduct PRS's. Findings are limited to a European ancestry sample. RESULTS: No genome-wide significant associations were found. Rs1813412 (chromosome 17) for regular cannabis use and rs62378502 (chromosome 5) for heaviness of cannabis use were approaching genome-wide significance. Both these SNPs were nominally significant (p<0.05) within males and females, however sex did not modify the association. The PRS identified statistically significant association with cannabis cravings. The variance explained by all PRSs were less than 1.02x10-2. CONCLUSION: This study provides promising results in understanding the genetic contribution to cannabis use in individuals living with OUD.
Cannabis , Opioid-Related Disorders , Humans , Male , Female , Cannabis/genetics , Genome-Wide Association Study/methods , Risk Factors , Opioid-Related Disorders/genetics , Multifactorial Inheritance , Genetic Predisposition to Disease
OBJECTIVES: The objective of our study was to identify outcomes reported in trials for older adults with depression and describe outcome heterogeneity. STUDY DESIGN AND SETTING: We searched four databases to identify trials assessing any intervention for major depressive disorder among older adults published between 2011 and 2021. We grouped reported outcomes thematically and mapped them onto core outcome areas (physiological/clinical, life impact, resource use, adverse events, and death) and used descriptive analysis to summarize outcome heterogeneity. RESULTS: There were 434 total outcomes reported by 49 included trials, which were measured using 135 different outcome measurement instruments and grouped into 100 unique outcome terms. Most outcome terms mapped to the physiological/clinical core area (47%), followed by life impact (42%). More than half of all terms (53%) were reported by only a single study. Most trials (n = 31/49) reported a single, discernible primary outcome. The most commonly reported outcome "depressive symptom severity" was assessed by 36 studies using 19 different outcome measurement instruments. CONCLUSION: There is substantial heterogeneity in the outcomes and outcome measurement instruments used in geriatric depression trials. A standard set of outcomes and accompanying measurement tools is necessary to facilitate comparison and synthesis of trial findings.
Depression , Depressive Disorder, Major , Humans , Aged , Depression/drug therapy , Depressive Disorder, Major/drug therapy
Importance: It is known that only minority of patients with opioid use disorder (OUD) receive treatment, of which only a fraction successfully complete treatment as intended. Factors associated with poor treatment outcomes remain unclear, and there is emerging but conflicting evidence that cannabis use may mitigate opioid use. Objective: To analyze predictors of relapse amongst patients receiving buprenorphine-naloxone for OUD and identify the association between cannabis use and time to relapse. Design: Data were prospectively collected between May 2018 and October 2020, and patients were followed for 12 months. Setting: Thirty-one outpatient opioid agonist treatment clinics across Ontario, Canada. Participants: All patients 16 years of age or older receiving buprenorphine-naloxone for OUD who had a urine toxicology screen negative for opioids at baseline were eligible for inclusion. Of the 488 patients consecutively sampled, 466 were included. Exposure: Cannabis use. Main outcome and measure: Relapse to opioid use assessed using urine toxicology screens. We employed a multivariable Cox-proportional hazard model for our analyses. Results: We found that cannabis use was not protective against relapse [hazard ratio (HR) = 1.03, 95% confidence interval (CI): 0.78, 1.36, p = 0.84]. We found that participants who have been in treatment for at least two years had a 44% decrease in the hazard of relapse compared to those in treatment for less than a year (HR = 0.56, 95% CI: 0.34, 0.92, p = 0.021). We also found that the hazard of relapse was 2.6 times higher for participants who were intravenous drug users (HR = 2.61, 95% CI: 1.74, 3.91, p < 0.001), and that for every 1mg increase in the participants' buprenorphine-naloxone dose, the hazard of relapse is 2% greater (HR = 1.02, 95% CI: 1.01, 1.03, p < 0.001). Conclusion: Our analysis failed to show cannabis to be protective against relapse to opioid use in patients receiving buprenorphine-naloxone for OUD. We identified that individuals who inject drugs, are on higher doses of buprenorphine-naloxone, or have been in treatment for less than two years have a higher hazard for relapse. The presence of such factors may thus warrant closer patient follow-up and more stringent treatment protocols to mitigate risk of relapse and potential overdose.
Introduction: Patient centred care is needed now more than ever in the treatment of opioid use disorder. Trials, policy makers, and service providers have most often used treatment retention and opioid urine screens as measures of treatment effectiveness. However, patients receiving medication for opioid use disorder treatment (MOUD) may prioritise the use of different ways to assess treatment success. Objective: The aim of this review is to synthesize literature examining the self-reported goals patients would like to achieve in MOUD for opioid use disorder. Methods: We searched MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform from inception until April 30th, 2021. No restrictions were placed on language, age, or type of MOUD. A qualitative synthesis is presented given that a meta-analysis was not possible. Results: The search yielded a total of 21,082 records from which 8 met criteria for inclusion in the qualitative synthesis. We identified a total of 43 patient-reported treatment goals from the 8 studies. Twelve domains were created from the 43 goals reported. These domains cover a range of important areas for patients' goals related to living a normal life, physical health, mental health, treatment, and substance use specific areas. Conclusion: This review highlights several patient goals that they would like to achieve during treatment for opioid use disorder that are not commonly considered as markers of treatment effectiveness. Goals related to health, living a normal life, and overall substance use concerns by patients should be taken into consideration by clinical trialists, researchers, policy makers, service providers, patients, and communities engaged in developing and tailoring treatment plans for opioid use disorder. Systematic Review Registration: PROSPERO CRD42018095553.
BACKGROUND: Suicidal behaviour remains a major public health concern and countries have responded by authoring guidelines to help mitigate death by suicide. Guidelines can include family-based recommendations, but evidence for the level and category of family-based involvement that is needed to effectively prevent suicide is unclear. AIMS: To explore the association between family-based recommendations in guidelines and countries' crude suicide rates. PROSPERO registration: CRD42019130195. METHOD: MEDLINE, Embase, PsycInfo, Web of Science and WHO MiNDbank databases and grey literature were searched within the past 20 years (1 January 2000 to 22 June 2020) for national guidelines giving family-based recommendations in any of three categories (prevention, intervention and postvention). RESULTS: We included 63 guidelines from 46 countries. All identified guidelines included at least one family-based recommendation. There were no statistically significant differences seen between mean World Health Organization crude suicide rates for countries that included only one, two or all three categories of family-based recommendations. However, a lower spread of crude suicide rates was seen when guideline recommendations included all three categories (mean crude suicide rates for one category: 11.09 (s.d. = 5.71); for two categories: 13.42 (s.d. = 7.76); for three categories: 10.68 (s.d. = 5.20); P = 0.478). CONCLUSIONS: Countries should work towards a comprehensive national suicide guideline that includes all categories of family-based recommendations. Countries with previously established guidelines should work towards the inclusion of evidence-based recommendations that have clear implementation plans to potentially help lower suicide rates.
Cannabinoids are commonly perceived by the public as safe and effective for improving mental health, despite limited evidence to support their use. We discuss reasons why cannabinoids may be particularly compelling for our patients and provide strategies for how psychiatrists can counsel and educate patients on the evidence regarding cannabinoids.
BACKGROUND: Amphetamine-type stimulants continue to dominate the global drug markets. Despite this, no pharmacotherapy has been approved for treatment of amphetamine and methamphetamine use disorder (AMD). We evaluate the efficacy of mirtazapine in the treatment of AMD, given emerging evidence that it may alleviate methamphetamine and amphetamine (MA/A) cravings and withdrawals. METHODS: We searched five databases from inception until January 28, 2021 for studies with a comparator group evaluating mirtazapine for treatment of AMD. We collected data on reduction in MA/A use, treatment retention, sexual behaviors, depression symptoms, cravings and adverse events. We assessed certainty of evidence using GRADE. Where appropriate, we conducted fixed-effect meta-analyses weighted by inverse variance and calculated the absolute risk reduction. RESULTS: Among the 206 studies screened, we included two parallel-arm placebo-controlled RCTs conducted among cis-gender men and transgender women (n = 180). We found that mirtazapine use likely results in a small reduction of methamphetamine use compared to placebo after 12-weeks (relative risk [RR]=0.81, 95% confidence interval [CI]: 0.63, 1.03; n = 133; moderate certainty evidence due to imprecision). We also found that the use of mirtazapine probably does not improve retention in treatment (RR=1.01, 95% CI: 0.91, 1.12; n = 180; moderate certainty evidence) or depression symptom severity (mean difference [MD]=0.45, 95% CI: -2.88, 3.78; n = 53; moderate certainty evidence). There were no serious adverse events. CONCLUSIONS AND RELEVANCE: Mirtazapine probably results in a small reduction in continued methamphetamine use among cisgender men and transgender women with AMD, but probably does not improve patients' retention in treatment or depression symptom severity. STUDY REGISTRATION: PROSPERO ID: CRD42021236806.
Central Nervous System Stimulants , Methamphetamine , Mirtazapine , Substance-Related Disorders , Central Nervous System Stimulants/adverse effects , Female , Humans , Male , Methamphetamine/adverse effects , Mirtazapine/therapeutic use , Remission Induction , Substance-Related Disorders/drug therapy
For many patients and healthcare providers, the move to virtual psychiatric care has been fast-tracked by the COVID-19 pandemic. In this article, we consider a patient perspective and a provider perspective on the transition to virtual psychiatric care and its strengths and limitations, as well as a call for much-needed future research.
OBJECTIVES: The opioid use disorder (OUD) crisis in North America has become "an epidemic within a pandemic" in the context of the COVID-19 virus. We aimed to explore the association between the COVID-19 pandemic and changes in opioid use patterns among patients receiving treatment for OUD. METHODS: We used prospectively collected data from 456 patients attending 31 opioid agonist clinics across Ontario, Canada. All included participants underwent routine urine drug screens (UDSs) both before and after the onset of the COVID-19 pandemic. A paired sample t -test was used to compare the proportion of opioid-positive UDSs collected pre- and post-pandemic, and linear regression analysis was used to explore factors associated with this change. RESULTS: Participants had a mean age of 39.9 years (standard deviation = 10.9), 52%were male, and 81%were receivingmethadone treatment. The percentage of opioid-positive UDSs increased significantly during the pandemic, on average by 10.6% (95% confidence interval [CI] 8.17, 12.95, P < 0.001). Continued opioid use before the pandemic was associated with 9.43% increase, on average, in the percentage of opioid-positive UDSs during the pandemic (95% CI 3.79, 15.07). Self-reported past-month cocaine (adjusted betacoefficient 6.83, 95% CI 0.92, 12.73) and amphetamine (adjusted beta-coefficient 13.13, 95% CI 5.15, 21.1) use at study entry were also associated with increases in opioid-positive UDSs. CONCLUSIONS: Increased opioid use is one measure of the negative impact the COVID-19 pandemic has had on individuals with OUD, an already marginalized population. Understanding factors associated with worse outcomes is essential to ensuring that treatment programs appropriately adapt to better serve this population during the pandemic.
COVID-19 , Opioid-Related Disorders , Adult , Analgesics, Opioid/therapeutic use , Female , Humans , Male , Ontario/epidemiology , Opiate Substitution Treatment , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/rehabilitation , Pandemics , Prospective Studies
BACKGROUND: The incidence of opioid-related fatality has reached unparalleled levels across North America. Patients with comorbid hepatitis C virus (HCV) remain the most vulnerable and difficult to treat. Considering the unique challenges associated with this population, we aimed to re-examine the impact of HCV on response to medication assistant treatment for opioid use disorder and establish sex-specific risk factors affecting care. METHODS: This study employs a multi-center prospective cohort design, with 1-year follow-up. Patients aged ≥18, receiving methadone for opioid use disorder were recruited from a network of outpatient opioid addiction treatment centers across Southern Ontario, Canada. Patients with ≥50% positive opioid urine screens over 1 year of follow-up were classified as poor responders. The prognostic impact of HCV on response was established using a propensity score matched analysis. Sex-specific regression models were constructed to evaluate risk factors for treatment response. RESULTS: Among participants eligible for inclusion (n = 1234), HCV was prevalent in 25% (n = 307). HCV patients exhibited significantly higher rates of high-risk opioid consumption patterns 35.29% (standard deviation 0.478). Sex-specific examination revealed females with HCV incur a 2 times increased risk for high-risk opioid consumption behaviors (female odds ratio: 1.95, 95% confidence interval 1.23, 3.10; P = 0.01). CONCLUSIONS: Findings from this study establish the link between HCV and poor treatment response, with differentially higher risk among female patients. In light of the high potential for overdose among this population, concerted efforts are required for distinguishing the source for sex-based disparities, in addition to establishing trauma and gender informed treatment protocols.
Hepatitis C , Opioid-Related Disorders , Analgesics, Opioid/therapeutic use , Female , Hepacivirus , Hepatitis C/complications , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Humans , Male , Ontario/epidemiology , Opiate Substitution Treatment/methods , Opioid-Related Disorders/complications , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Prospective Studies , Risk Factors
Genetic variants in the OPRM1 and CYP2B6 genes, respectively coding for an opioid receptor and methadone metabolizers, have been linked to negative treatment outcomes in patients undergoing methadone maintenance treatment, with little consensus on their effect. This study aims to test the associations between pre-selected SNPs of OPRM1 and CYP2B6 and outcomes of continued opioid use, relapse, and methadone dose. It also aims to observe differences in associations within the sexes. 1,172 participants treated with methadone (nMale = 666, nFemale = 506) were included in this study. SNPs rs73568641 and rs7451325 from OPRM1 and all the tested CYP2B6 SNPs were detected to be in high linkage disequilibrium. Though no associations were found to be significant, noteworthy differences were observed in associations of OPRM1 rs73568641 and CYP2B6 rs3745274 with treatment outcomes between males and females. Further research is needed to determine if sex-specific differences are present.
Cytochrome P-450 CYP2B6/genetics , Receptors, Opioid, mu/genetics , Substance-Related Disorders/genetics , Adult , Alleles , Analgesics, Opioid/therapeutic use , Cytochrome P-450 CYP2B6/metabolism , Female , Gene Frequency/genetics , Genotype , Humans , Linkage Disequilibrium/genetics , Male , Methadone/therapeutic use , Ontario/epidemiology , Opiate Substitution Treatment/methods , Opioid-Related Disorders/drug therapy , Polymorphism, Single Nucleotide/genetics , Receptors, Opioid, mu/metabolism , Recurrence , Sex Characteristics , Sex Factors , Substance-Related Disorders/metabolism , Treatment Outcome
