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Abstract Objective Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2‐item scale polygenic score with anxiety in MS. Methods Using a case–control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview‐diagnosed, and lifetime self‐report physician‐diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome‐wide association study and was tested using regression. Results A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta‐analyses identified that in MS, each 1‐SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09–1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease. Interpretation Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.

Abstract Background Postpartum depression and anxiety are major public health concerns that affect 3–39% of women after childbearing and can adversely affect maternal and child health. Most studies have investigated postpartum depression and anxiety and their associated factors among women 4–12 weeks after delivery. There is a scarcity of research among women immediately after delivery from low- and middle-income countries, the gap this study aimed to fill. Methods A descriptive cross-sectional study was conducted among 386 postpartum women within one week after delivery. The Edinburg Postnatal Depression Scale was used to assess depressive symptoms and the Generalized Anxiety Disorder − 7 scale was used to screen for symptoms of generalized anxiety disorder. Participants were systematically selected from the postnatal wards and interviewed by trained research assistants from November 2019 to March 2020. Results Using standard cut points, the prevalence of depressive and anxiety symptoms was 25.39%, and 37.31% respectively. Having a baby with a weight of 2.5 kgs or more and having partner support were associated with decreased odds of both depression and anxiety symptoms. In contrast, complications during delivery, caesarian section, marital status, and partner violence, were associated with increased odds of depressive and anxiety symptoms post-delivery. Conclusion There was a high prevalence of postpartum depression and anxiety symptoms among the study participants in the first week post-delivery, with delivery complications and outcome and psychosocial supports identified as associated factors for depression and anxiety symptoms. These findings highlight the need for early screening to identify those at risk for appropriate intervention.

Abstract Background The transition from childhood to adolescence is associated with an increase in rates of some psychiatric disorders, including major depressive disorder, a debilitating mood disorder. The aim of this systematic review is to update the evidence on the benefits and harms of screening for depression in primary care and non-mental health clinic settings among children and adolescents. Methods This review is an update of a previous systematic review, for which the last search was conducted in 2017. We searched Ovid MEDLINE® ALL, Embase Classic+Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and CINAHL on November 4, 2019, and updated on February 19, 2021. If no randomized controlled trials were found, we planned to conduct an additional search for non-randomized trials with a comparator group. For non-randomized trials, we applied a non-randomized controlled trial filter and searched the same databases except for Cochrane Central Register of Controlled Trials from January 2015 to February 2021. We also conducted a targeted search of the gray literature for unpublished documents. Title and abstract, and full-text screening were completed independently by pairs of reviewers. Results In this review update, we were unable to find any randomized controlled studies that satisfied our eligibility criteria and evaluated the potential benefits and harms of screening for depression in children and adolescents. Additionally, a search for non-randomized trials yielded no studies that met the inclusion criteria. Conclusions The findings of this review indicate a lack of available evidence regarding the potential benefits and harms of screening for depression in children and adolescents. This absence of evidence emphasizes the necessity for well-conducted clinical trials to evaluate the effectiveness of depression screening among children and adolescents in primary care and non-mental health clinic settings. Systematic review registration PROSPERO CRD42020150373 .

Abstract Background Major depressive disorder is common, debilitating, and affects feelings, thoughts, mood, and behaviors. Childhood and adolescence are critical periods for the development of depression and adolescence is marked by an increased incidence of mental health disorders. This protocol outlines the planned scope and methods for a systematic review update that will evaluate the benefits and harms of screening for depression in children and adolescents. Methods This review will update a previously published systematic review by Roseman and colleagues. Eligible studies are randomized controlled trials (RCTs) assessing formal screening in primary care to identify children or adolescents not already self-reporting symptoms of, diagnosed with, or treated for depression. If no or only a single RCT is available, we will consider controlled studies without random assignment. Studies of participants with characteristics associated with an elevated risk of depression will be analyzed separately. Outcomes of interest are symptoms of depression, classification of major depressive disorder based on a validated diagnostic interview, suicidality, health-related quality of life, social function, impact on lifestyle behavior (e.g., substance use, school performance, lost time at work, or school), false-positive results, overdiagnosis, overtreatment, labeling, and other harms such as those arising from treatment. We will search MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, and grey literature sources. Two reviewers will independently screen the titles and abstracts using the liberal accelerated method. Full-text screening will be performed independently by two reviewers using pre-specified eligibility criteria. Data extraction and risk of bias assessments will be performed independently by two reviewers. Pre-planned analyses, including subgroup and sensitivity analyses, are detailed within this protocol. Two independent reviewers will assess and finalize through consensus the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and prepare GRADE evidence profiles and summary of findings tables for each outcome of interest. Discussion The systematic review will provide a current state of the evidence of benefits and harms of depression screening in children and adolescents. These findings will be used by the Canadian Task Force on Preventive Health Care to inform the development of recommendations on depression screening. Systematic review registration PROSPERO CRD42020150373

Abstract Background Self-help may reduce the risk of depression, and risk perception of depression may influence initiating self-help. It is unknown how risk perception is associated with self-help behaviours. The objectives of this study are to (1) describe the self-help strategies used by high-risk Canadians in relation to the accuracy of perceived depression risk, by sex, and (2) identify demographic and clinical factors associated with self-help behaviours. Methods Baseline data from a randomized controlled trial including 358 men and 356 women at high-risk of developing depression were used. Following methods used in cancer research, risk perception accuracy was determined by comparing the participant’s self-perceived and objective risk of developing depression and classifying as accurate, over-estimation and under-estimation based on a ± 10% threshold. The participant’s objective depression risk was assessed using sex-specific multivariable risk predictive algorithms. Frequency of using 14 self-help strategies was assessed. One-way ANOVA testing was used to detect if differences in risk perception accuracy groups existed, stratified by sex. Linear regression was used to investigate the clinical and demographic factors associated with self-help behaviours, also stratified. Results Compared to accurate-estimators, male over-estimators were less likely to “leave the house daily,” and “participate in activities they enjoy.” Male under-estimators were also less likely to “participate in activities they enjoy.” Both male ‘inaccurate’ perception groups were more likely to ‘create lists of strategies which have worked for feelings of depression in the past and use them’. There were no significant differences between self-help behaviours and risk perception accuracy in women. Regression modeling showed negative relationships between self-rated health and self-help scores, irrespective of sex. In women, self-help score was positively associated with age and educational attainment, and negatively associated with perceived risk. In men, a positive relationship with unemployment was also seen. Conclusions Sex differences exist in the factors associated with self-help. Risk perception accuracy, work status, and self-rated health is associated with self-help behaviours in high-risk men. In women, factors related to self-help included age, education, self-rated health status, and perceived risk. More research is needed to replicate findings. Trial registration Prospectively registered at ClinicalTrials.gov ( NCT02943876 ) as of 10/21/16.

Abstract Background Major depressive disorder is one of the most prevalent and disabling forms of mental illness in the general population. One public health strategy that may reduce the disease burden is early identification and prevention - identifying people who are at high risk and intervening to prevent symptoms from progressing into a major depressive episode (MDE). Multivariable risk predictive algorithms (MVRP) have been developed to estimate personalized risk (probability) of an MDE. The purpose of this trial is to answer the questions: (1) Does disclosure of personalized depression risk information promote high-risk individuals to take preventive actions? (2) Will disclosure of personalized depression risk information negatively affect the mental health of those at high risk? Methods We are recruiting 350 high-risk men and 350 high-risk women across the country. Individuals are eligible, if they: (1) are 18 years or older, (2) have not had a depressive episode in the past two months, (3) are at high risk of MDE based on the MVRPs (predicted risk of 6.5% + for men and of 11.2% + for women), (4) can communicate in either English or French, and (5) agree to be contacted for follow-up interviews. The MVRPs were developed and validated using longitudinal data from over 10,000 Canadians across the country. Eligible participants are randomized into (1) the control group, and (2) the group receiving personalized depression risk information. The participants are assessed at baseline, 6 and 12 months regarding accuracy of risk perception, use of self-help strategies and changes in psychological distress and functioning. Qualitative interviews are conducted in sub-samples of the intervention groups to explore how the personalized information affects risk perception, self-help behaviors and mental health. Discussion MVRPs can be used for risk stratification and planning preventive actions. The personalized risk information produced by MVRPs may also empower users to actively engage in self-management. This trial will contribute to the knowledge base about the potential health benefits and psychological harms associated with the provision of personalized depression risk information that will inform future implementation and patient-physician communication in the clinical settings. Trial registration NCT02943876. Date of trial registration: October 21st, 2016.

Abstract Background Because the collection of mental health information through interviews is expensive and time consuming, interest in using population-based administrative health data to conduct research on depression has increased. However, there is concern that misclassification of disease diagnosis in the underlying data might bias the results. Our objective was to determine the validity of International Classification of Disease (ICD)-9 and ICD-10 administrative health data case definitions for depression using review of family physician (FP) charts as the reference standard. Methods Trained chart reviewers reviewed 3362 randomly selected charts from years 2001 and 2004 at 64 FP clinics in Alberta (AB) and British Columbia (BC), Canada. Depression was defined as presence of either: 1) documentation of major depressive episode, or 2) documentation of specific antidepressant medication prescription plus recorded depressed mood. The charts were linked to administrative data (hospital discharge abstracts and physician claims data) using personal health numbers. Validity indices were estimated for six administrative data definitions of depression using three years of administrative data. Results Depression prevalence by chart review was 15.9–19.2% depending on year, region, and province. An ICD administrative data definition of ‘2 depression claims with depression ICD codes within a one-year window OR 1 discharge abstract data (DAD) depression diagnosis’ had the highest overall validity, with estimates being 61.4% for sensitivity, 94.3% for specificity, 69.7% for positive predictive value, and 92.0% for negative predictive value. Stratification of the validity parameters for this case definition showed that sensitivity was fairly consistent across groups, however the positive predictive value was significantly higher in 2004 data compared to 2001 data (78.8 and 59.6%, respectively), and in AB data compared to BC data (79.8 and 61.7%, respectively). Conclusions Sensitivity of the case definition is often moderate, and specificity is often high, possibly due to undercoding of depression. Limitations to this study include the use of FP charts data as the reference standard, given the potential for missed or incorrect depression diagnoses. These results suggest that that administrative data can be used as a source of information for both research and surveillance purposes, while remaining aware of these limitations.

Abstract Background In 2018, the World Health Organization reported that depression is the most common cause of disability worldwide, with over 300 million people currently living with depression. Depression affects an individual’s physical health and well-being, impacts psychosocial functioning, and has specific negative short- and long-term effects on maternal health, child health, developmental trajectories, and family health. The aim of these reviews is to identify evidence on the benefits and harms of screening for depression in the general adult population and in pregnant and postpartum women. Methods Search strategies were developed and tested through an iterative process by an experienced medical information specialist in consultation with the review team. We will search MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library, and a randomized controlled trial filter will be used. The general adult review will be an update of a systematic review previously used by the Canadian Task Force on Preventive Health Care for their 2013 guideline recommendation. The search strategy will be updated and will start from the last search date of the previous review (May 2012). The pregnant and postpartum review will be a de novo review with no date restriction. For both reviews, we will search for unpublished documents following the CADTH Grey Matters checklist and relevant websites. Titles and abstracts will be screened using the liberal accelerated method. Two reviewers will independently screen full-text articles for relevance using pre-specified eligibility criteria and assess the risk of bias of included studies using the Cochrane Risk of Bias tool. Outcomes of interest for the general adult population review include symptoms of depression or diagnosis of major depressive disorder, health-related quality of life, day-to-day functionality, lost time at work/school, impact on lifestyle behaviour, suicidality, false-positive result, labelling/stigma, overdiagnosis or overtreatment, and harms of treatment. Outcomes of interest for the pregnant and postpartum review include mental health outcomes (e.g. diagnosis of major depressive disorder), parenting outcomes (e.g. mother-child interactions), and infant outcomes (e.g. infant health and development). Discussion These two systematic reviews will offer informative evaluations of depression screening. The findings will be used by the Task Force to help develop guideline recommendations on depression screening in the general adult population and in pregnant and postpartum women in Canada. Systematic review registration PROSPERO (CRD42018099689, CRD42018099690)

Background: We aimed to determine the relationship between childhood abuse and mental ill-health in firefighters deployed to a devastating fire that engulfed Fort McMurray Methods: A stratified sample of 282 firefighters was selected from a cohort of 1234 for assessment by Structured Clinical Interview (SCID) for DSM-5 diagnostic criteria and the Childhood Experience of Care and Abuse questionnaire (CECA-Q). Diagnoses were grouped as post-traumatic stress disorder (PTSD), anxiety disorders, depressive disorders and substance use disorders. Scales extracted from the CECA-Q included parental loss, antipathy, neglect, physical punishment, sexual abuse and support from a same-age confidant. The relation to diagnostic group was examined by multivariable logistic regression Results: 192 SCID interviews and 188 CECA-Qs were completed: 124 met DSM-5 criteria for diagnoses including anxiety disorder (56), depressive disorder (54), PTSD (77) and substance use disorder (43). Childhood sexual abuse was reported by 24 firefighters all of whom met DSM-5 diagnostic criteria. Sexual abuse and a childhood confidant differentiated diagnoses in an initial multivariable model of those with psychiatric disorders. Compared to those without a psychiatric diagnosis, father's antipathy was related to anxiety and substance use, physical punishment to PTSD and substance use. A childhood same-age confidant protected against anxiety, depression and PTSD. Fire exposures related only to PTSD. Limitations: The comparison group without mental disorders was small. Childhood abuse information was collected retrospectively and may be biased by current state. Conclusions: Firefighters’ mental health is a function of both work-role traumas and childhood events. Occupational health provision must address this complexity.

BackgroundIn June 2013, the city of Calgary, Alberta and surrounding areas sustained significant flooding which resulted in large scale evacuations and closure of businesses and schools. Floods can increase stress which may negatively impact perinatal outcomes and mental health, but previous research is inconsistent. The objectives of this study are to examine the impact of the flood on pregnancy health, birth outcomes and postpartum mental health.MethodsLinked administrative data from the province of Alberta were used. Outcomes included preterm birth, small for gestational age, a new diagnoses of preeclampsia or gestational hypertension, and a diagnosis of, or drug prescription for, depression or anxiety. Data were analyzed using a quasi-experimental difference in difference design, comparing flooded and non-flooded areas and in affected and unaffected time periods. Multivariable log binomial regression models were used to estimate risk ratios, adjusted for maternal age. Marginal probabilities for the difference in difference term were used to show the potential effect of the flood.ResultsParticipants included 18,266 nulliparous women for the pregnancy outcomes, and 26,956 women with infants for the mental health analysis. There were no effects for preterm birth (DID 0.00, CI: -0.02, 0.02), small for gestational age (DID 0.00, CI: -0.02, 0.02), or new cases of preeclampsia (DID 0.00, CI: -0.01, 0.01). There was a small increase in new cases of gestational hypertension (DID 0.02, CI: 0.01, 0.03) in flood affected areas. There were no differences in postpartum anxiety or depression prescriptions or diagnoses.ConclusionThe Calgary 2013 flood was associated with a minor increase in gestational hypertension and not other health outcomes. Universal prenatal care and magnitude of the disaster may have minimized impacts of the flood on pregnant women.

Abstract Background Depression affects over 400 million people globally. The majority are seen in primary care. Barriers in providing adequate care are not solely related to physicians’ knowledge/skills deficits, but also time constraints, lack of confidence/avoidance, which need to be addressed in mental health-care redesign. We hypothesized that family physician (FP) training in the Adult Mental Health Practice Support Program (AMHPSP) would lead to greater improvements in patient depressive symptom ratings (a priori primary outcome) compared to treatment as usual. Methods From October 2013 to May 2015, in a controlled trial 77 FP practices were stratified on the total number of physicians/practice as well as urban/rural setting, and randomized to the British Columbia AMHPSP⎯a multi-component contact-based training to enhance FPs’ comfort/skills in treating mild-moderate depression (intervention), or no training (control) by an investigator not operationally involved in the trial. FPs with a valid license to practice in NS were eligible. FPs from both groups were asked to identify 3–4 consecutive patients > 18 years old, diagnosis of depression, Patient Health Questionnaire (PHQ-9) score ≥ 10, able to read English, intact cognitive functioning. Exclusion criteria: antidepressants within 5 weeks and psychotherapy within 3 months of enrollment, and clinically judged urgent/emergent medical/psychiatric condition. Patients were assigned to the same arm as their physician. Thirty-six practices recruited patients (intervention n = 23; control n = 13). The study was prematurely terminated at 6 months of enrollment start-date due to concomitant primary health-care transformation by health-system leaders which resulted in increased in-office demands, and recruitment failure. We used the PHQ-9 to assess between-group differences at baseline, 1, 2, 3, and 6 months follow-up. Outcome collectors and assessors were blind to group assignment. Results One hundred-and-twenty-nine patients (intervention n = 72; control n = 57) were analysed. A significant improvement in depression scores among intervention group patients emerged between 3 and 6 months, time by treatment interaction, likelihood ratio test (LR) chi2(3) = 7.96, p = .047. Conclusions This novel skill-based program shows promise in translating increased FP comfort and skills managing depressed patients into improved patient clinical outcomes⎯even in absence of mental health specialists availability. Trial registration #NCT01975948.

Introduction: Several regions in Canada have recently experienced sharp increases in opioid overdoses and related hospitalizations and deaths. This paper describes opioid-related mortality and disability from opioid use disorder in Canada from 1990 to 2014 using data from the Global Burden of Disease (GBD) study. Methods: We used data from the GBD study to describe temporal trends (1990–2014) in opioid-related mortality and disability from opioid use disorder using common metrics: disability-adjusted life years (DALY), deaths, years of life lost (YLL) and years lived with disability (YLD). We also compared age-standardized YLL and DALY rates per 100 000 population between Canada, the USA and other regions. Results: The age-standardized opioid-related DALY rate in Canada was 355.5 per 100 000 population in 2014, which was higher than the global rate of 193.2, but lower than the rate of 767.9 in the United States. Between 1990 and 2014, the age-standardized opioid-related YLL rate in Canada increased by 142.2%, while globally this rate decreased by 10.1%. In comparison with YLL, YLD accounted for a larger proportion of the overall opioid-related burden across all age groups. Health loss was greater for males than females, and highest among those aged 25 to 29 years. Conclusion: The health burden associated with opioid-related mortality and disability from opioid use disorder in Canada is significant and has increased dramatically from 1990 to 2014. These data point to a need for public health action including enhanced monitoring of a range of opioid-related harms.

Introduction. Plusieurs régions du Canada ont récemment connu de brusques hausses de surdoses d’opioïdes ainsi que des hospitalisations et des décès connexes. Cet article traite de la mortalité liée aux opioïdes et de l'invalidité découlant d'un trouble de consommation d’opioïdes au Canada entre 1990 et 2014, à la lumière des données de l’Étude sur la charge mondiale de morbidité (ÉCMM). Méthodologie. Nous avons utilisé les données de l’ÉCMM pour décrire l'évolution (1990 à 2014) en matière de mortalité liée aux opioïdes et d’invalidité découlant d’un trouble de consommation d’opioïdes en calculant les années de vie ajustées du facteur invalidité (AVAI), les décès, les années de vie perdues (AVP) et les années vécues avec invalidité (AVI). Nous avons également comparé les taux d’AVP et d’AVAI pour 100 000 au Canada, aux États-Unis et dans d'autres régions. Résultats. Le taux normalisé selon l’âge d’AVAI lié aux opioïdes au Canada était de 355,5 par 100 000 en 2014, soit un taux supérieur au taux mondial de 193,2 mais inférieur au taux de 767,9 aux États-Unis. Entre 1990 et 2014, le taux normalisé selon l’âge d’AVP attribuables aux opioïdes a augmenté de 142,2 % au Canada alors qu’il a diminué de 10,1 % à l’échelle mondiale. Les AVI ont contribué à une plus grande proportion du fardeau global lié aux opioïdes que les AVP, et ce, dans tous les groupes d’âge. La perte de santé a été plus importante chez les hommes que chez les femmes, et particulièrement marquée chez les 25 à 29 ans. Conclusion. Le fardeau sur la santé dû à la mortalité liée aux opioïdes et à l’invalidité découlant d’un trouble de consommation d’opioïdes au Canada est important et s’est considérablement alourdi entre 1990 et 2014. Ces données révèlent la nécessité d’agir en santé publique, notamment par le renforcement de la surveillance des divers méfaits liés aux opioïdes.

Introduction Pregnant women are often concerned about the impact of antidepressant medication use on their pregnancy, such as congenital abnormalities. This concern may vary in a way that depends on the class of antidepressant medication prescribed. Objectives and Approach This study examined the rate of adherence and persistence to antidepressants based on the class of antidepressants prescribed during pregnancy This is a retrospective cohort study using population-based administrative data in Alberta– linking delivery record, hospitalization data, physician claims data, emergency department data, and prescription medication data. The eligible study population included women with depression who gave birth between 2012-2015, and were adherent (medication possession ratio ≥80%) to ≥ 2 consecutive antidepressant prescriptions during the preconception year (n=1,865). The rates of adherence and persistence (prescription refill gap ≤30 days) were calculated by medication class and were compared using chi-square tests. Results During pregnancy, 834 (44.7%) women completely stopped taking antidepressants. Among those taking antidepressants, the overall rate of adherence was 62.6% (95% CI: 59.4%, 65.7%). The rate differed significantly by medication class (p

Introduction Pooling data from cohort studies can be used to increase sample size. However, individual datasets may contain variables that measure the same construct differently, posing challenges in the usefulness of combined datasets. Variable harmonization (an effort that provides comparable view of data from different studies) may address this issue. Objectives and Approach This study harmonized existing datasets from two prospective pregnancy cohort studies in Alberta Canada (All Our Families (n=3,351) and Alberta Pregnancy Outcome and Nutrition (n=2,187)). Given the comparability of the characteristics of the two cohorts and similarities of the core data elements of interest, data harmonization was justifiable. Data harmonization was performed considering multiple factors, such as complete or partial variable matching regarding question asked/responded, the response coded (value level, value definition, data type), the frequency of measurement, the pregnancy time-period of measurement, and missing values. Multiple imputation was used to address missing data resulting from the data harmonization process. Results Several variables such as ethnicity, income, parity, gestational age, anxiety, and depression were harmonized using different procedures. If the question asked/answered and the response recorded was the same in both datasets, no variable manipulation was done. If the response recorded was different, the response was re-categorized/re-organized to optimize comparability of data from both datasets. Missing values were created for each resulting unmatched variables and were replaced using multiple imputation if the same construct was measured in both datasets but using different ways/scales. A scale that was used in both datasets was identified as a reference standard. If the variables were measured in multiple times and/or different time-periods, variables were synchronized using pregnancy trimesters data. Finally, harmonized datasets were then combined/pooled into a single dataset (n=5,588). Conclusion/Implications Variable harmonization is an important aspect of conducting research using multiple datasets. It provides an opportunity to increase study power through maximizing sample size, permitting more sophisticated statistical analyses, and to answer novel research questions that could not be addressed using a single study.

Depression is prevalent in primary biliary cholangitis (PBC) patients. Our aims were to examine the effects of depression and antidepressants on hepatic outcomes of PBC patients.We used the UK Health Improvement Network database to identify PBC patients between 1974 and 2007. Our primary outcome was one of three clinical events: decompensated cirrhosis, liver transplantation and death. We assessed depression and each class of antidepressant medication in adjusted multivariate Cox proportional hazards models to identify independent predictors of outcomes. In a sensitivity analysis, the study population was restricted to PBC patients using ursodeoxycholic acid (UDCA).We identified 1,177 PBC patients during our study period. In our cohort, 86 patients (7.3%) had a depression diagnosis prior to PBC diagnosis, while 79 patients (6.7%) had a depression diagnosis after PBC diagnosis. Ten-year incidence of mortality, decompensated cirrhosis, and liver transplantation were 13.4%, 6.6%, and 2.0%, respectively. In our adjusted models, depression status was not a predictor of poor outcomes. After studying all classes of antidepressants, using the atypical antidepressant mirtazapine after PBC diagnosis was significantly protective (Adjusted HR 0.23: 95% CI 0.07-0.72) against poor liver outcomes (decompensation, liver transplant, mortality), which remained statistically significant in patients using UCDA (HR 0.21: 95% CI 0.05-0.83).In our study, depression was not associated with poor clinical outcomes. However, using the antidepressant mirtazapine was associated with decreased mortality, decompensated cirrhosis and liver transplantation in PBC patients. These findings support further assessment of mirtazapine as a potential treatment for PBC patients.