Protocol for a qualitative study exploring the pharmacist's role in supporting postsecondary students with psychotropic medication management.

INTRODUCTION: Findings from the National College Health Assessment (2019) stated that anxiety and depression are the most prevalent diagnosed mental illnesses among Canadian postsecondary students with one-fifth of students self-reporting a lifetime diagnosis. Psychotropic medications can be an important component of a multifaceted approach to the management and treatment of mental illness and are the most commonly dispensed via community pharmacies. Community pharmacies provide an opportunity for pharmacists to have a prominent role in supporting patients' psychotropic medication management. However, there has been limited exploration of how pharmacists can address patients' psychotropic medication management needs, experiences and opportunities for improvements especially for emerging adults. METHODS AND ANALYSIS: This qualitative study will incorporate Thorne's approach to interpretative description. Purposeful snowball sampling will be used to identify students (18-25 years) taking psychotropic medication(s) to manage their mental health. Participants will be interviewed one on one using a semistructured interview guide virtually. Inductive thematic analysis is underway with data analysis being iterative and reflexive using NVivo. Information provided from the interviews will be reviewed and summarised into key themes. ETHICS AND DISSEMINATION: This study was approved by the University of Toronto Health Sciences Research Ethics Board (REB #43185). It is expected that there will be a very low risk for mild psychological and social harm for participants as they will have the ability to stop the interview at any time and will be aware of confidentiality. The results from this study will be used to create or adapt healthcare team services including the role of pharmacists within the healthcare ecosystem at the university and contribute to developing the next stage of research to evaluate feasibility and effectiveness of programmes at the university that help postsecondary students to manage psychotropic medication.

Pharmacists as Personalized Medicine Experts (PRIME): Experiences Implementing Pharmacist-Led Pharmacogenomic Testing in Primary Care Practices.

Research exploring the integration of pharmacogenomics (PGx) testing by pharmacists into their primary care practices (including community pharmacies) has focused on the "external" factors that impact practice implementation. In this study, additional "internal" factors, related to the capabilities, opportunities, and motivations of pharmacists that influence their ability to implement PGx testing, were analyzed. Semi-structured interview data from the Pharmacists as Personalized Medicine Experts (PRIME) study, which examined the barriers and facilitators to implementing PGx testing by pharmacists into primary care practice, were analyzed. Through thematic analysis, using the theoretical domains framework (TDF) domains as deductive codes, the authors identified the most relevant TDF domains and applied the behavioural change wheel (BCW) to generate intervention types to aid in the implementation of PGx testing. Pharmacists described how their professional identities, practice environments, self-confidence, and beliefs in the benefits of PGx impacted their ability to provide a PGx-testing service. Potential interventions to improve the implementation of the PGx service included preparing pharmacists for managing an increased patient load, helping pharmacists navigate the software and technology requirements associated with the PGx service, and streamlining workflows and documentation requirements. As interest in the wide-scale implementation of PGx testing through community pharmacies grows, additional strategies need to address the "internal" factors that influence the ability of pharmacists to integrate testing into their practices.

The Role of the Pharmacist in the Care of Patients with Chronic Pain.

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.

Evaluating comparative effectiveness of psychosocial interventions adjunctive to opioid agonist therapy for opioid use disorder: A systematic review with network meta-analyses.

BACKGROUND: Guidelines recommend that individuals with opioid use disorder (OUD) receive pharmacological and psychosocial interventions; however, the most appropriate psychosocial intervention is not known. In collaboration with people with lived experience, clinicians, and policy makers, we sought to assess the relative benefits of psychosocial interventions as an adjunct to opioid agonist therapy (OAT) among persons with OUD. METHODS: A review protocol was registered a priori (CRD42018090761), and a comprehensive search for randomized controlled trials (RCT) was conducted from database inception to June 2020 in MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials. Established methods for study selection and data extraction were used. Primary outcomes were treatment retention and opioid use (measured by urinalysis for opioid use and opioid abstinence outcomes). Odds ratios were estimated using network meta-analyses (NMA) as appropriate based on available evidence, and in remaining cases alternative approaches to synthesis were used. RESULTS: Seventy-two RCTs met the inclusion criteria. Risk of bias evaluations commonly identified study limitations and poor reporting with regard to methods used for allocation concealment and selective outcome reporting. Due to inconsistency in reporting of outcome measures, only 48 RCTs (20 unique interventions, 5,404 participants) were included for NMA of treatment retention, where statistically significant differences were found when psychosocial interventions were used as an adjunct to OAT as compared to OAT-only. The addition of rewards-based interventions such as contingency management (alone or with community reinforcement approach) to OAT was superior to OAT-only. Few statistically significant differences between psychosocial interventions were identified among any other pairwise comparisons. Heterogeneity in reporting formats precluded an NMA for opioid use. A structured synthesis was undertaken for the remaining outcomes which included opioid use (n = 18 studies) and opioid abstinence (n = 35 studies), where the majority of studies found no significant difference between OAT plus psychosocial interventions as compared to OAT-only. CONCLUSIONS: This systematic review offers a comprehensive synthesis of the available evidence and the limitations of current trials of psychosocial interventions applied as an adjunct to OAT for OUD. Clinicians and health services may wish to consider integrating contingency management in addition to OAT for OUD in their settings to improve treatment retention. Aside from treatment retention, few differences were consistently found between psychosocial interventions adjunctive to OAT and OAT-only. There is a need for high-quality RCTs to establish more definitive conclusions. TRIAL REGISTRATION: PROSPERO registration CRD42018090761.

Understanding the effects of chronic benzodiazepine use in depression: a focus on neuropharmacology.

Benzodiazepines are frequently prescribed on an ongoing basis to individuals with depression, mainly to alleviate anxiety or insomnia, despite current guideline recommendations that continuous use should not exceed 4 weeks. Currently, there are no efficacy trials published beyond 8 weeks. Several antidepressant trials demonstrate that the concomitant use of a benzodiazepine is associated with poorer depressive outcomes and functional status; however, it is unclear why this is the case. Patients with depression receiving a benzodiazepine may reflect a more ill or high anxiety group, although even within anxiety disorders, the use of a benzodiazepine is associated with poorer outcomes. The neuroadaptive consequences of long-term benzodiazepine use may be a factor underlying these findings. Chronic benzodiazepine use results in decreased gamma-aminobutyric acid and monoaminergic function, as well as interference with neurogenesis, which are all purported to play a role in antidepressant efficacy. This review will discuss the oppositional neuropharmacological interactions between chronic benzodiazepine use and antidepressant mechanism of action, which could result in reduced antidepressant efficacy and function in depression.

A Continuing Professional Development Program for Pharmacists Implementing Pharmacogenomics into Practice.

A continuing professional development (CPD) program for pharmacists practicing in community and team-based primary care settings was developed and evaluated using Moore's framework for the assessment of continuing medical education. The program had three components: online lectures, a two-day training workshop, and patient case studies. Knowledge (pre-post multiple choice test); attitudes, readiness, and comfort with applying pharmacogenomics in their practices (pre-post surveys); and experiences of implementing pharmacogenomics in practice (semi-structured interviews) were assessed. Twenty-one of 26 enrolled pharmacists successfully completed the program, and were satisfied with their experience. Almost all achieved a score of 80% or higher on the post-training multiple choice test, with significantly improved scores compared to the pre-training test. Pre- and post-training surveys demonstrated that participants felt that their knowledge and competence increased upon completion of the training. In the follow-up, 15 pharmacists incorporated pharmacogenomics testing into care for 117 patients. Ten pharmacists participated in semi-structured interviews, reporting strong performance in the program, but some difficulty implementing new knowledge in their practices. This multi-component CPD program successfully increased pharmacists' knowledge, readiness, and comfort in applying pharmacogenomics to patient care in the short-term, yet some pharmacists struggled to integrate this new service into their practices.

Improving opioid guideline adherence: evaluation of a multifaceted, theory-informed pilot intervention for family physicians.

OBJECTIVES: Opioid-related deaths continue to increase in North America, an epidemic that was initiated by high rates of opioid prescribing. We designed a multifaceted, theory-informed Opioid Self-Assessment (OSA) package, to increase adherence to the Canadian Opioid Guideline among family physicians. This study aimed to assess changes in Canadian family physicians' knowledge and practices after completing the OSA package. DESIGN: We conducted a mixed-method evaluation using a pre-test and post-test design that involved the collection of both qualitative and quantitative data. SETTING: This research was conducted in the primary care setting in Ontario, Canada. PARTICIPANTS: We recruited a purposive sample of nine family physicians in Ontario who use long-term opioid therapy to treat patients with chronic pain. INTERVENTIONS: The OSA package included four components: an online knowledge test, an online learning programme, a safe medication practice self-assessment questionnaire and chart audit with feedback. OUTCOME MEASURES: Our measures included changes in knowledge, opioid safety practices and physicians' perspectives on the OSA package. RESULTS: We found statistically significant improvements between pre-test and post-test knowledge scores at both baseline and 6-month follow-up. Physicians' scores improved significantly on five of the seven core characteristics of the practice self-assessment questionnaire. On the chart audits, we observed an improvement in patient education between baseline and 6 months. Qualitative interviews showed that participants appreciated embedded resources in the OSA package. The completion of the package stimulated identification of gaps or deficits in practice and served as a useful reminder to discuss risk and safety with patients. Participants described the chart review as helpful in prompting discussions with their patients, identifying deficits and strengths and a 'primary motivator' for project participation. CONCLUSIONS: The OSA package has the potential to improve medication safety practices in primary care related to opioid monitoring and adherence to current opioid guidelines.

Impact of timing of methadone initiation on perinatal outcomes following delivery among pregnant women on methadone maintenance therapy in Ontario.

BACKGROUND AND AIMS: Methadone maintenance therapy (MMT) is associated with improved outcomes for children exposed to maternal opioid dependence in utero. We examined Ontario's population of pregnant women on MMT and determined the impact of timing of MMT initiation on perinatal outcomes. DESIGN: Cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women eligible for public drug benefits and on MMT during pregnancy between 2005 and 2015. MEASUREMENTS: We stratified women based on their timing of MMT initiation: (1) stabilized prior to conception, (2) newly initiated prior to conception, (3) initiation in trimester 1, (4) initiation in trimester 2 or (5) initiation in trimester 3. The primary outcomes in the multivariable logistic regression analysis were key perinatal health indicators: small for gestational age, preterm birth, congenital anomalies, severe maternal morbidity, caesarean section and induced labor. Secondary outcomes were specific to maternal opioid dependence: neonatal abstinence syndrome (NAS), admission to a neonatal intensive care unit (NICU), NAS treatment, removal from mother's custody at hospital discharge and neonatal death. FINDINGS: Among 1842 women on MMT during pregnancy, 87.6% (n = 1614) initiated MMT before conception. Almost a quarter of their infants (22.2%; n = 408) were born small for gestational age, 17.5% (n = 323) were preterm and 5.9% (n = 109) were born with a congenital anomaly. The odds of primary outcomes occurring did not differ based on timing of methadone initiation; however, infants of mothers who initiated methadone during pregnancy had up to a fourfold increase in the odds of social services removal at the hospital [adjusted odds ratio (aOR) range = 3.70-4.19] compared with those whose mothers were stabilized on MMT prior to conception. CONCLUSIONS: Later initiation of methadone maintenance therapy among pregnant women in Ontario, Canada has not been found to be clearly related to most key perinatal adverse health outcomes.

Evaluating comparative effectiveness of psychosocial interventions for persons receiving opioid agonist therapy for opioid use disorder: protocol for a systematic review.

INTRODUCTION: The opioid crisis has resulted in increasing rates of death caused by problematic opioid use. Current clinical guidelines recommend that individuals with persons with opioid use disorder (OUD) receive pharmacological (eg, opioid agonist therapy) and psychosocial (eg, cognitive behavioural therapy) therapy; however, the best combination of pharmacologic and psychosocial components is not known. Our objective of the planned study is to conduct a comprehensive systematic review to assess the relative benefits of psychosocial interventions as an adjunct to opioid agonist therapy among persons with OUD. METHODS AND ANALYSIS: A comprehensive search for randomised controlled trials published in English or French will be conducted from database inception to March 2018. The search will be conducted in MEDLINE and translated for Embase, PsycINFO and the Cochrane Central Register of Controlled Trials. Two independent reviewers will screen, extract and assess risk of bias of eligible articles. Primary outcomes of interest will be treatment retention and opioid use (based on urinalysis results). Secondary outcomes will include self-reported opioid use, abstinence from illicit drugs, adherence to psychosocial therapy and opioid agonist therapy, risk for sexually transmitted disease, risk for blood borne pathogens, changes in mental health symptoms (eg, depression), measures of craving and changes in patients' quality of life and relevant adverse events. If sufficient data and adequate homogeneity exists, network meta-analyses (NMA) will be performed. ETHICS AND DISSEMINATION: This will be the first systematic review to incorporate NMA to compare psychosocial treatments used as an adjunct to opioid agonist therapy for OUD. Results of this review will inform clinical management of persons with OUD. TRIAL REGISTRATION NUMBER: CRD42018090761.

Cardiovascular and Neuropsychiatric Events after Varenicline Use for Smoking Cessation.

RATIONALE: Varenicline aids in smoking cessation but has also been associated with serious adverse events. OBJECTIVES: The aim of this study was to determine the risks of cardiovascular and neuropsychiatric events after varenicline receipt in a real-world setting. METHODS: A population-based, self-controlled risk interval study using linked universal health administrative data from the diverse, multicultural population of Ontario, Canada, was conducted. In two separate analyses, new varenicline users between September 1, 2011 and February 15, 2014 were observed from 1 year before to 1 year after varenicline receipt. The relative incidences of cardiovascular and neuropsychiatric hospitalizations and emergency department visits in the 12 weeks after varenicline receipt (the risk interval) compared with the remaining observation period (the control interval) were estimated in two separate fixed-effect conditional Poisson regressions. Sensitivity analyses tested the robustness of the results. MEASUREMENTS AND MAIN RESULTS: Among 56,851 new users of varenicline, 6,317 cardiovascular and 10,041 neuropsychiatric hospitalizations and emergency department visits occurred from 1 year before to 1 year after receipt. The incidence of cardiovascular events was 34% higher in the risk compared with the control interval (relative incidence, 1.34; 95% confidence interval, 1.25-1.44). Findings were consistent in sensitivity analyses, most notably in those without any history of previous cardiovascular disease. The relative incidence of neuropsychiatric events was marginally significant in the primary (relative incidence, 1.06; 95% confidence interval, 1.00-1.13) but not all sensitivity analyses. CONCLUSIONS: Varenicline appears to be associated with an increased risk of cardiovascular but not neuropsychiatric events.

Impact of large-scale distribution and subsequent use of free nicotine patches on primary care physician interaction.

BACKGROUND: Large-scale distribution efforts of free nicotine replacement therapy (NRT) have been documented to be cost-effective interventions for increasing smoking quit rates. However, despite nearly a dozen studies evaluating their effectiveness, none have examined whether free NRT provision promotes further primary care help-seeking and the impact that it may have on cessation efforts. METHODS: In the context of a randomized controlled trial, a secondary analysis was conducted on 1000 adult regular smokers randomized to be mailed a 5-week supply of nicotine patches or to a no intervention control group. Recipients and users of free nicotine patches at an 8 week follow-up were successfully case matched to controls based on age, gender, baseline level of nicotine dependence and intent to quit (n = 201 per group). Differences in physician interaction between the two groups were evaluated at both 8 week and 6 month follow-ups. The impact of physician interaction on self-reported smoking abstinence at each follow-up was also examined. RESULTS: Although no differences in physician interaction were noted between groups at the 8 week follow-up, at the 6 month follow-up, nicotine patch users reported greater frequency of discussing smoking with their physician (43.9%), as compared to the control group (30.3%) (p = 0.011). Across both groups, over 90% of those that discussed smoking with a physician were encouraged to quit and approximately 70% were provided with additional support. Separate ANOVAs revealed no significant impact of physician interaction on cessation (p > 0.05), regardless of group or follow-up period, however, at the 6 month follow-up, nicotine patch users who discussed cessation with a physician had made serious quit attempts at significantly greater rates (72.6%), compared to controls (49.1%) (p = 0.007). CONCLUSIONS: Irrespective of group, the majority of smokers in the present study did not discuss cessation with their physician. Recipients and users of nicotine patches however, were more likely to discuss smoking with their physician, suggesting that the provision of free NRT particularly to those who are likely to use it may facilitate opportunities for benefits beyond the direct pharmacological effects of the medication. TRIAL REGISTRATION: clinicaltrials.gov , NCT01429129 . Registered: 2 September 2011.

Mailed distribution of free nicotine patches without behavioral support: Predictors of use and cessation.

INTRODUCTION: There is growing evidence that the mailed distribution of free nicotine replacement therapy (NRT), usually as part of smokers' helplines, can been effective in increasing the odds of cessation on a population level. However, limited information is available on the utilization of NRT when it is provided for free, and factors associated with regimen adherence have remained largely unexplored. METHODS: In the context of a randomized controlled trial, 500 adult smokers across Canada hypothetically interested in free NRT were mailed a 5week supply of nicotine patches, but no other support was offered. Analyses evaluated which a priori-defined demographic and smoking characteristics predicted nicotine patch use at 8week follow-up of 421 patch recipients, as well as examined the association between patch use and smoking cessation at 6months. RESULTS: At 8weeks, 10.9% had used all, 47.5% had used some but not all, and 41.6% had not used any of the provided nicotine patches. Lower age, unemployment, past NRT use and intent to quit in the next 30days at baseline (preparation stage of change) were all identified as independent predictors of some nicotine patch use. Only use of all patches was associated with greater odds of smoking cessation, compared to non-users (Adj. OR=2.96; 95%CI=1.06-8.27). CONCLUSIONS: The mailed distribution of free nicotine patches to smokers at large can be effective at promoting cessation, particularly among financially disadvantaged groups, those with previous NRT experience and among individuals with already advanced intent to quit.

Sex and gender-based analysis in pharmacy practice research: A scoping review.

BACKGROUND: Recognizing the potential effect of sex and gender on health outcomes, there is a shift toward conducting sex and gender-based analysis (SGBA) within health research. However, little is known about the extent to which SGBA has been incorporated into pharmacy practice research. OBJECTIVES: To understand the extent to which SGBA is included in pharmacy practice research. METHOD: Scoping review of English-language studies identified through MEDLINE, Embase, International Pharmacy Abstracts (IPA), and CINAHL (inception to Jan 2014). Two raters independently screened citations to identify titles and abstracts that included key words related to sex or gender and studies that could be categorized as pharmacy practice research. One author extracted data from included studies related to study design, population, intervention/exposure and outcomes, with results reviewed by another. All authors reviewed eligible articles to categorize them based on a previously-developed typology, and to assess four criteria: 1) the inclusion of sex or gender in research objectives, 2) the depth of sex/gender analysis incorporated into study designs and reporting, 3) the inclusion of sex or gender considerations in interpretation of study results, 4) the intentional and accurate use of sex/gender language. RESULTS: Of 458 unique search results, only six articles met the inclusion criteria. Two of these six publications included sex/gender considerations in a model consistent with sex/gender based analysis as described by Hammarström. Three of the six studies inaccurately applied sex and gender terminology, whereas the two studies that featured sex or gender in their primary research question did use these terms appropriately. CONCLUSION: Despite increasing attention on the need for considering sex and gender, there was a paucity of pharmacy practice research publications that conducted SGBA. This presents an opportunity to explore sex, gender and intersectionality when pursuing studies that explore the impact of pharmacists interventions on patient outcomes.

Impact of self-reported lifetime depression or anxiety on effectiveness of mass distribution of nicotine patches.

BACKGROUND: Large-scale public health initiatives providing free nicotine replacement therapy have been shown to increase smoking cessation rates; however, their effectiveness among the highly prevalent population of smokers with depression and anxiety disorders has not been explored. The aim of this study was to investigate the influence of lifetime history of depression or anxiety on smoking cessation success following the free distribution of nicotine patches. METHOD: In the context of a randomised controlled trial, a secondary analysis was conducted on 1000 adult regular smokers randomised to be mailed a 5-week supply of nicotine patches or to a no intervention control group. Participants were divided into subgroups based on the presence of self-reported lifetime diagnosis of depression and anxiety. RESULTS: Irrespective of self-reported lifetime history of depression or anxiety, odds of self-reported cessation at 6 months were significantly greater among groups receiving nicotine patches compared to no intervention control (no history of depression or anxiety: OR 2.20; 95% CI 1.05 to 4.63; history of depression or anxiety present: OR 3.90; 95% CI 1.28 to 11.88). Among nicotine patch recipients only, quit outcomes did not differ between those with and without self-reported lifetime depression or anxiety in models unadjusted and adjusted for differences in demographic and smoking characteristics. CONCLUSIONS: The mass distribution of free nicotine patches (without behavioural support) is effective among smokers with or without lifetime history of depression or anxiety alike, providing further support for the adoption of similar initiatives as a means of promoting tobacco cessation on a population level. TRIAL REGISTRATION NUMBER: NCT01429129, Post-results.

Assessing anhedonia in depression: Potentials and pitfalls.

The resurgence of interest in anhedonia within major depression has been fuelled by clinical trials demonstrating its utility in predicting antidepressant response as well as recent conceptualizations focused on the role and manifestation of anhedonia in depression. Historically, anhedonia has been understood as a "loss of pleasure", yet neuropsychological and neurobiological studies reveal a multifaceted reconceptualization that emphasizes different facets of hedonic function, including desire, effort/motivation, anticipation and consummatory pleasure. To ensure generalizability across studies, evaluation of the available subjective and objective methods to assess anhedonia is necessary. The majority of research regarding anhedonia and its neurobiological underpinnings comes from preclinical research, which uses primary reward (e.g. food) to probe hedonic responding. In contrast, behavioural studies in humans primarily use secondary reward (e.g. money) to measure many aspects of reward responding, including delay discounting, response bias, prediction error, probabilistic reversal learning, effort, anticipation and consummatory pleasure. The development of subjective scales to measure anhedonia has also increased in the last decade. This review will assess the current methodology to measure anhedonia, with a focus on scales and behavioural tasks in humans. Limitations of current work and recommendations for future studies are discussed.

Approach to the pharmacological management of chronic pain in patients with an alcohol use disorder.

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.

Correlates of benzodiazepine use in major depressive disorder: The effect of anhedonia.

BACKGROUND: Current treatment guidelines emphasize the limited role of benzodiazepines in Major Depressive Disorder (MDD), mainly due to the absence of long-term data, risk of abuse and potential adverse effects. However, benzodiazepines continue to be prescribed for long-term use in a significant number of patients. This study sought to evaluate benzodiazepine use in a large sample of MDD patients seen at a tertiary care clinic, and determine whether use is related to illness severity or complexity, as well as to identify the clinical predictors of benzodiazepine use. METHODS: This was a naturalistic cross-sectional study conducted in MDD patients seen at the Mood Disorders Pyschopharmacology Unit at the University Health Network (N=326). Detailed information on current medication regimens was collected. A structured diagnostic interview, in addition to measures of symptom severity, quality of life, and personality were administered. Participants were grouped according to the presence or absence of prescribed benzodiazepines for daily use. RESULTS: The prevalence of regular benzodiazepine use was 25%. Benzodiazepine users were more likely to be female, unemployed, have a history of child abuse, and have comorbid panic disorder. Depression and anxiety scores were not significantly different between groups, although anhedonia was greater in the benzodiazepine group. A logistic regression revealed anhedonia was the strongest predictor of regular benzodiazepine use. CONCLUSION: The groups were similar in clinical profile suggesting benzodiazepine use is not necessarily linked to greater illness complexity or severity. Benzodiazepine use appears to be associated with specific diagnostic and symptom characteristics, possibly providing insight into the potential pharmacodynamic and neurobiological effects of frequent use.

Development and validation of the Dimensional Anhedonia Rating Scale (DARS) in a community sample and individuals with major depression.

Anhedonia, a core symptom of Major Depressive Disorder (MDD), is predictive of antidepressant non-response. In contrast to the definition of anhedonia as a "loss of pleasure", neuropsychological studies provide evidence for multiple facets of hedonic function. The aim of the current study was to develop and validate the Dimensional Anhedonia Rating Scale (DARS), a dynamic scale that measures desire, motivation, effort and consummatory pleasure across hedonic domains. Following item selection procedures and reliability testing using data from community participants (N=229) (Study 1), the 17-item scale was validated in an online study with community participants (N=150) (Study 2). The DARS was also validated in unipolar or bipolar depressed patients (n=52) and controls (n=50) (Study 3). Principal components analysis of the 17-item DARS revealed a 4-component structure mapping onto the domains of anhedonia: hobbies, food/drink, social activities, and sensory experience. Reliability of the DARS subscales was high across studies (Cronbach's α=0.75-0.92). The DARS also demonstrated good convergent and divergent validity. Hierarchical regression analysis revealed the DARS showed additional utility over the Snaith-Hamilton Pleasure Scale (SHAPS) in predicting reward function and distinguishing MDD subgroups. These studies provide support for the reliability and validity of the DARS.