Psychotropic medications and mortality from cardiovascular disease and suicide for individuals with depression in Taiwan.

BACKGROUND: Polypharmacy for treatment of depression has been increasing in Taiwan. METHODS: Individuals having depressive disorders were identified in a national database for healthcare services and followed up for 5 years. The mean dosage of antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics was calculated; the associations between the exposure dosage to different psychotropic medications and patients' overall death and death due to cardiovascular diseases (CVD) and suicide were examined. RESULTS: A total of 400,042 individuals with depressive disorders (63.8% women) were identified. Compared with those with no exposure to antidepressants, patients prescribed antidepressants had decreased mortality. Use of antipsychotics had a dose-related increase in overall mortality risk compared to no exposure group. Contrarily, depressed patients taking sedative-hypnotics had decreased overall and CVD mortality compared to no exposure group, with the most prominent decrease in CVD mortality of up to 54.9% for those in the moderate exposure group (hazard ratio: 0.451, 95% confidence interval: 0.405-0.503). A moderate or high dose of antidepressants or sedative-hypnotics was shown to be associated with a significantly increased mortality for suicide compared to those with no exposure. CONCLUSIONS: Antidepressant and sedative-hypnotic use was associated with decreased all-cause and CVD-related mortality and use of antipsychotics was associated with a dose-related increase in mortality risk. Future studies are needed to further clarify the involved mechanisms and benefits and risks should be carefully weighed when prescribing psychotropic medications in patients with depressive disorders.

Suicidal behavior and all-cause mortality in depressed older adults aged 75+ treated with electroconvulsive therapy: A Swedish register-based comparison study.

OBJECTIVES: Electroconvulsive therapy (ECT) is effective in treating late-life depression. There is limited research on suicidal behavior and all-cause mortality in the oldest old after ECT. METHODS: Older adults aged 75 years and above who had been inpatients for moderate to severe depression between January 1, 2011, and December 31, 2017, were included in the study. We used exact and propensity score matching to balance groups. We compared suicidal behavior (fatal and non-fatal) and all-cause mortality in those who had received ECT and those with other depression treatments. RESULTS: Of the study population, 1802 persons who received ECT were matched to 4457 persons with other treatments. There were no significant differences in the risk of suicidal behavior between groups, (within 3 months: odds ratio 0.73; 95% confidence intervals (CI), 0.44-1.23, within 4 months to 1 year: aOR 1.34; 95% CI, 0.84-2.13). All-cause mortality was lower among ECT recipients compared to those who had received other treatments, both within 3 months (aOR, 0.35; 95% CI, 0.23-0.52), and within 4 months to 1 year (aOR 0.65; 95% CI, 0.50-0.83). CONCLUSIONS: Compared to other depression treatments, ECT is not associated with a higher risk of suicidal behavior in patients aged 75 and above. ECT is associated with lower all-cause mortality in this age group, but we advise caution regarding causal inferences.

Mortality and adverse events associated with statin use in primary care patients with depression: a real-world, population-based cohort study.

BACKGROUND: New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established. OBJECTIVES: This study aims to assess the real-world mortality and adverse events of statins in depressive disorders. METHODS: Population-based, nationwide (England), between-subject, cohort study. We used electronic health records (QResearch database) of people aged 18-100 years with first-episode depression, registered with English primary care practices over January 1998-August 2020 for 12(+) months, divided into statin users versus non-users.Primary safety outcomes included all-cause mortality and any adverse event measured at 2, 6 and 12 months. Multivariable logistic regression was employed to control for several potential confounders and calculate adjusted ORs (aORs) with 99% CIs. FINDINGS: From over 1 050 105 patients with depression (42.64% males, mean age 43.23±18.32 years), 21 384 (2.04%) died, while 707 111 (67.34%) experienced at least one adverse event during the 12-month follow-up. Statin use was associated with lower mortality over 12 months (range aOR2-12months 0.66-0.67, range 99% CI 0.60 to 0.73) and with lower adverse events over 6 months (range aOR2-6months 0.90-0.96, range 99% CI 0.91 to 0.99), but not at 1 year (aOR12months 0.99, 99% CI 0.96 to 1.03). No association with any other individual outcome measure (ie, any other neuropsychiatric symptoms) was identified. CONCLUSIONS: We found no evidence that statin use among people with depression increases mortality or other adverse events. CLINICAL IMPLICATIONS: Our findings support the safety of updated NICE guidelines for prescribing statins in people with depressive disorders.

Frailty as a Predictor of Mortality in Late-Life Depression: A Prospective Clinical Cohort Study.

OBJECTIVE: Frailty is a clinical phenotype that predicts negative health outcomes, including mortality, and is increasingly used for risk stratification in geriatric medicine. Similar to frailty, late-life depression is also associated with increased mortality rates. Therefore, we examined whether frailty and frailty-related biomarkers predict mortality among depressed older patients. METHODS: In our study of 378 older patients aged ≥ 60 years with a depressive disorder (DSM-IV criteria), we examined whether frailty predicts time-to-death during a 6-year follow-up using Cox proportional hazard regression analyses adjusted for confounders. Baseline data were collected from 2007 to September 2010. Frailty was defined according to the Fried Frailty Phenotype criteria (muscle weakness, slowness, exhaustion, low activity level, unintended weight loss). Similarly, we examined the predictive value of 3 inflammatory markers, vitamin D level, and leukocyte telomere length and whether these effects were independent of the frailty phenotype. RESULTS: During follow-up, 27 (26.2%) of 103 frail depressed patients died compared with 35 (12.7%) of 275 non-frail depressed patients (P < .001). Adjusted for confounders, the number of frailty components was associated with an increased mortality rate (hazard ratio = 1.38 [95% CI, 1.06-1.78], P = .015). All biomarkers except for interleukin 6 were prospectively associated with mortality, but only higher levels of high-sensitivity C-reactive protein and lower levels of vitamin D were independent of frailty associated with mortality. CONCLUSIONS: In late-life depression, frailty identifies older patients at increased risk of adverse negative health outcomes. Therefore, among frail depressed patients, treatment models that include frailty-specific interventions might reduce mortality rates.

Psychiatric problems of anxiety and depression disorder are associated with medical service utilization and survival among patients with cervical cancer.

OBJECTIVE: There are few nationwide studies regarding the long-term analysis of cervical cancer patients in Taiwan. Thus, this study aimed to evaluate medical service utilization, and survival among cervical cancer patients initially diagnosed with or without anxiety and/or depressive disorders. MATERIALS AND METHODS: This was a retrospective longitudinal study using data from the National Health Insurance Research Database from 1996 to 2010. The study subjects were cervical cancer patients identified by ICD-9-CM codes 180.X, while subjects with anxiety and/or depressive disorders were identified using the following codes: 300.0X-300.9X (minus 300.4X) for anxiety disorder, and 296.2X, 296.3X, 300.4, and 311.X for depressive disorder. The cervical patients with anxiety or/and depression disorder were classified as anxiety/depression (AD) group or the non-disorder (ND) group. Propensity score matching (PSM) was used to adjust for differences between the AD and ND groups. T-tests were used to evaluate differences in medical utilization and the Kaplan-Meier method was used to evaluate survival conditions between the two groups. Statistical analyses were performed using SPSS Statistics 20.0. RESULTS: A total of 3664 patients were identified, with 862 (23.5%) having anxiety, 149 (4.1%) with depression, and 349 (9.5%) having both anxiety and depression. In total, 1360 cervical cancer patients had anxiety/depression disorders. After PSM, the AD group had significantly more outpatient department (OPD) visits than the ND group (p < 0.001) but the survival status was better in the AD group than the ND group (p < 0.001). CONCLUSIONS: Cervical cancer patients with anxiety/depression disorders visited the OPD more frequently than those without anxiety/depression disorders but had better survival status. Gynecologists should also consider cancer patients' mental status during follow-up, referring patients to psychiatric professionals for appropriate psychiatric care if appropriate.

Multimorbidity patterns and their relationship to mortality in the US older adult population.

BACKGROUND: Understanding patterns of multimorbidity in the US older adult population and their relationship with mortality is important for reducing healthcare utilization and improving health. Previous investigations measured multimorbidity as counts of conditions rather than specific combination of conditions. METHODS: This cross-sectional study with longitudinal mortality follow-up employed latent class analysis (LCA) to develop clinically meaningful subgroups of participants aged 50 and older with different combinations of 13 chronic conditions from the National Health Interview Survey 2002-2014. Mortality linkage with National Death Index was performed through December 2015 for 166,126 participants. Survival analyses were conducted to assess the relationships between LCA classes and all-cause mortality and cause specific mortalities. RESULTS: LCA identified five multimorbidity groups with primary characteristics: "healthy" (51.5%), "age-associated chronic conditions" (33.6%), "respiratory conditions" (7.3%), "cognitively impaired" (4.3%) and "complex cardiometabolic" (3.2%). Covariate-adjusted survival analysis indicated "complex cardiometabolic" class had the highest mortality with a Hazard Ratio (HR) of 5.30, 99.5% CI [4.52, 6.22]; followed by "cognitively impaired" class (3.34 [2.93, 3.81]); "respiratory condition" class (2.14 [1.87, 2.46]); and "age-associated chronic conditions" class (1.81 [1.66, 1.98]). Patterns of multimorbidity classes were strongly associated with the primary underlying cause of death. The "cognitively impaired" class reported similar number of conditions compared to the "respiratory condition" class but had significantly higher mortality (3.8 vs 3.7 conditions, HR = 1.56 [1.32, 1.85]). CONCLUSION: We demonstrated that LCA method is effective in classifying clinically meaningful multimorbidity subgroup. Specific combinations of conditions including cognitive impairment and depressive symptoms have a substantial detrimental impact on the mortality of older adults. The numbers of chronic conditions experienced by older adults is not always proportional to mortality risk. Our findings provide valuable information for identifying high risk older adults with multimorbidity to facilitate early intervention to treat chronic conditions and reduce mortality.

Excess mortality and shortened life expectancy in people with major mental illnesses in Taiwan.

AIMS: Given the concerns of health inequality associated with mental illnesses, we aimed to reveal the extent of which general mortality and life expectancy at birth in people with schizophrenia, bipolar disorder and depressive disorder varied in the 2005 and 2010 nationally representative cohorts in Taiwan. METHODS: Two nationally representative samples of individuals with schizophrenia, bipolar disorder and depressive disorder were identified from Taiwan's national health insurance database in 2005 and 2010, respectively, and followed-up for consecutive 3 years. The database was linked to nationwide mortality registry to identify causes and date of death. Age-, gender- and cause-specific mortality rates were generated, with the average follow-up period of each age- and gender-band applied as 'weighting' for the calculation of expected number of deaths. Age- and gender-standardised mortality ratios (SMRs) were calculated for these 3-year observation periods with Taiwanese general population in 2011/2012 as the standard population. The SMR calculations were then stratified by natural/unnatural causes and major groups of death. Corresponding life expectancies at birth were also calculated by gender, diagnosis of mental disorders and year of cohorts for further elucidation. RESULTS: The general differential in mortality rates for people with schizophrenia and bipolar disorder remained wide, revealing an SMR of 3.65 (95% confidence interval (CI): 3.55-3.76) for cohort 2005 and 3.27 (3.18-3.36) for cohort 2010 in schizophrenia, and 2.65 (95% CI: 2.55-2.76) for cohort 2005 and 2.39 (2.31-2.48) for cohort 2010 in bipolar disorder, respectively. The SMRs in people with depression were 1.83 (95% CI: 1.81-1.86) for cohort 2005 and 1.59 (1.57-1.61) for cohort 2010. SMRs due to unnatural causes tended to decrease in people with major mental illnesses over the years, but those due to natural causes remained relatively stable. The life expectancies at birth for schizophrenia, bipolar disorder and depression were all significantly lower than the national norms, specifically showing 14.97-15.50 years of life lost for men and 15.15-15.48 years for women in people with schizophrenia. CONCLUSIONS: Compared to general population, the differential in mortality rates for people with major mental illnesses persisted substantial. The differential in mortality for unnatural causes of death seemed decreasing over the years, but that due to natural causes remained relatively steady. Regardless of gender, people with schizophrenia, bipolar disorder and depression were shown to have shortened life expectancies compared to general population.

Association of End Point Definition and Randomized Clinical Trial Duration in Clinical Trials of Schizophrenia Medications.

Importance: Facilitating the development of safe and effective medications for schizophrenia is a public health imperative. Objectives: To evaluate the association of shortening randomized clinical trial (RCT) duration with the modification of the Positive and Negative Syndrome Scale (PANSS) for the design of RCTs of medications for schizophrenia and to offer perspective on an alternative regulatory pathway to the historically accepted trial duration and response assessment. Data Sources: A database was created consisting of clinical trial data from 32 placebo-controlled RCTs of 8 atypical antipsychotic drugs approved by the US Food and Drug Administration (FDA) between January 1, 2001, and December 31, 2015. The database included information on total and individual PANSS item ratings, demographic characteristics, disposition, and adverse events (AEs). Study Selection: All clinical trials submitted to 8 new drug applications of atypical antipsychotic drugs were selected. Data Extraction and Synthesis: Quality control checks were performed to ensure that the collected data were consistent with the reported results of each trial. Data were collected from March 15, 2015, to September 30, 2015. Data analysis was conducted from October 1, 2015, to June 20, 2016. Main Outcomes and Measures: The following analyses were performed: (1) longitudinal assessment of mean change from baseline in total PANSS score, (2) correlation analyses between change from baseline in total PANSS score at week 6 and earlier time points, (3) concordance analyses of outcomes across trials between week 6 and earlier time points using total PANSS and modified PANSS, and (4) analyses of time course of treatment-emergent AEs. Results: The final database contained data from 14 219 participants enrolled in 32 drug trials; 9805 of 14 219 participants (69.0%) were male and were either white (7183 [50.5%]) or black (4346 [30.6%]) individuals. The mean (SD) age during treatment was 38.9 (10.9) years, and the mean (SD) age at schizophrenia diagnosis was 25 (8.5) years. Statistically significant separation between treatment response and placebo response was observed after 1 week of treatment. The overall concordance rate across treatment groups steadily increased from week 1 to week 4 (68.0% for week 1, 74.0% for week 2, 83.0% for week 3, and 93.0% for week 4). Trends in AE occurrence were evident by week 1 and percentage of AEs were similar across weeks 3, 4, and 6. The overall concordance rate between change from baseline in the modified PANSS score and change from baseline in the total PANSS score was 93.0% (80 of 86 treatment groups) at week 4 and 97.7% (84 of 86 treatment groups) at week 6. Shortening the trial duration to 4 weeks increased the required sample size to 502 participants. Using the modified PANSS as the end point, the sample size for a 4-week trial was 402 participants and 296 participants for a 6-week trial. Conclusions and Relevance: Findings from this analysis suggest that there is the potential to streamline the design of schizophrenia drug clinical trials. Trial sponsors may consider incorporating these strategies and are encouraged to consult with the FDA early in the drug development process.

Mortality in patients with psychogenic nonepileptic seizures.

OBJECTIVE: To investigate the hypothesis that patients diagnosed with psychogenic nonepileptic seizures (PNES) on video-EEG monitoring (VEM) have increased mortality by comparison to the general population. METHODS: This retrospective cohort study included patients evaluated in VEM units of 3 tertiary hospitals in Melbourne, Australia, between January 1, 1995, and December 31, 2015. Diagnosis was based on consensus opinion of experienced epileptologists and neuropsychiatrists at each hospital. Mortality was determined in patients diagnosed with PNES, epilepsy, or both conditions by linkage to the Australian National Death Index. Lifetime history of psychiatric disorders in PNES was determined from formal neuropsychiatric reports. RESULTS: A total of 5,508 patients underwent VEM. A total of 674 (12.2%) were diagnosed with PNES, 3064 (55.6%) with epilepsy, 175 (3.2%) with both conditions, and 1,595 (29.0%) received other diagnoses or had no diagnosis made. The standardized mortality ratio (SMR) of patients diagnosed with PNES was 2.5 (95% confidence interval [CI] 2.0-3.3). Those younger than 30 had an 8-fold higher risk of death (95% CI 3.4-19.8). Direct comparison revealed no significant difference in mortality rate between diagnostic groups. Among deaths in patients diagnosed with PNES (n = 55), external causes contributed 18%, with 20% of deaths in those younger than 50 years attributed to suicide, and "epilepsy" was recorded as the cause of death in 24%. CONCLUSIONS: Patients diagnosed with PNES have a SMR 2.5 times above the general population, dying at a rate comparable to those with drug-resistant epilepsy. This emphasizes the importance of prompt diagnosis, identification of risk factors, and implementation of appropriate strategies to prevent potential avoidable deaths.

Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries.

Importance: Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live. Objective: To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas. Design, Setting, and Participants: This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019. Exposures: Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview. Main Outcomes and Measures: Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality. Results: Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend < .001). The associations between having 4 or more depressive symptoms and the combined outcome were similar in 7 different geographical regions and in countries at all economic levels but were stronger in urban (HR, 1.23; 95% CI, 1.13-1.34) compared with rural (HR, 1.10; 95% CI, 1.02-1.19) communities (P for interaction = .001) and in men (HR, 1.27; 95% CI, 1.13-1.38) compared with women (HR, 1.14; 95% CI, 1.06-1.23; P for interaction < .001). Conclusions and Relevance: In this large, population-based cohort study, adults with depressive symptoms were associated with having increased risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide.

Relationship of non-melancholic and melancholic depressive symptoms with all-cause mortality: A prospective study in a primary care population.

OBJECTIVE: To assess relationship of non-melancholic and melancholic subtypes of depressive symptoms with all-cause mortality among cardiovascular risk persons. METHODS: A population-based prospective study of 2522 Finnish middle-aged persons with elevated cardiovascular risk was conducted. Depressive symptoms were assessed by the Beck's Depression Inventory. Data on mortality were obtained from The Official Statistics of Finland after 11-year follow-up. RESULTS: At baseline, the prevalence of non-melancholic and melancholic depressive symptoms was 14.9% and 5.2%, respectively. During the mean follow-up time of 11 years, 8.1% (n = 164) of those without, 13.9% (n = 52) of those with non-melancholic, and 10.7% (n = 14) of those with melancholic depressive symptoms died. Compared to non-depressive subjects, the hazard ratio for time to all-cause mortality was 1.67 (95% CI: 1.21-2.32, p = .002) in non-melancholically depressive and 1.01 (95% CI: 0.56-1.83, p = .97) in melancholically depressive subjects, when adjusted for age, gender, education, smoking, alcohol use, BMI, hypertension, dyslipidaemia, and glucose disorders. In comparison to the mortality rate in the general population throughout Finland over the same period, non-depressiveness was associated with a decreased standardized mortality rate. CONCLUSION: Non-melancholic depressive symptoms seem to be associated with excess all-cause mortality. In clinical settings, recognition of non-melancholic depressive symptoms should be emphasised.

A Post-Authorization Safety Study of Quetiapine as Antidepressant Treatment in Sweden: Nested Case-Control Analyses of Select Outcomes.

INTRODUCTION: This post-authorization safety study (PASS) was a commitment to the European Medicines Agency. OBJECTIVE: This PASS investigated quetiapine as antidepressant treatment in Swedish registers with regard to the risk for all-cause mortality, self-harm and suicide, acute myocardial infarction, stroke, diabetes mellitus, extrapyramidal disorders, and somnolence. METHODS: Users of quetiapine and antidepressants (2011‒2014) who had changed treatment in the past year were included. Conditional logistic regression models were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for each outcome in nested case-control studies for quetiapine as combination therapy and monotherapy, monotherapy with antidepressants, and no medication, versus the use of combinations of antidepressants (reference group). RESULTS: Overall, 7421 quetiapine users and 281,303 antidepressant users were included. For quetiapine in combination, risks were increased for all-cause mortality [adjusted OR (aOR) 1.31, 95% CI 1.12-1.54] compared with combinations of antidepressants; however, when stratified by age, only patients ≥ 65 years of age had an increased mortality, and, in a post hoc analysis excluding patients with Parkinson's disease, no mortality increase remained. Furthermore, the risk for self-harm and suicide was increased (aOR 1.53, 95% CI 1.31-1.79), but when stratified by age, the risk increase was found only among patients aged 18-64 years. Risks were also increased for stroke among patients ≥ 65 years of age (aOR 1.47, 95% CI 1.01-2.12), for extrapyramidal disorder (aOR 6.15, 95% CI 3.57-10.58), and for somnolence (aOR 2.41, 95% CI 1.42-4.11). CONCLUSION: Risks for all-cause mortality, self-harm and suicide, and stroke in older patients may be higher among patients treated with quetiapine and antidepressant combination therapy.

Mortality during US FDA clinical trials in patients with diabetes, hypertension, depression and schizophrenia.

Objectives: To evaluate the relationship between the mortality rates associated with psychiatric conditions like depression and schizophrenia compared with chronic medical conditions like hypertension and diabetes.Methods: Examined clinical trial safety data from New Drug Approval programmes reviewed by the US Food and Drug Administration and calculated all-cause and suicide/non-suicide mortality rates per 100,000 patient-exposure-years (PEY) for seven diabetes, 12 hypertension, 11 depression, and nine schizophrenia programmes (126,151 patients, 63,106.3 PEY).Results: Depression (894.8 ± 201.2) and schizophrenia (935.3 ± 214.6) had significantly higher all-cause mortality rates than diabetes (462.8 ± 70.8) and hypertension (448.4 ± 123.1). Psychiatric conditions had 1.9-2.1× the medical conditions' mortality (p < 0.001). Non-suicide mortality rates for depression (506.2 ± 151.3), schizophrenia (550.9 ± 164.7), diabetes (457.2 ± 70.4) and hypertension (430.8 ± 120.6) were comparable. Only antidiabetics showed a signal for all-cause mortality (reduction of 37%, p = 0.008).Conclusions: Depression and schizophrenia trial patients had comparable (if not higher) all-cause mortality rates as older populations in diabetes and hypertension trials, even when excluding suicides. While generalizability of the rates themselves is limited, this study can adequately estimate the relational mortality among these conditions because of the high internal consistency of clinical trials. Potential signals for mortality reduction with active treatment should be considered for all investigational medications for chronic conditions with increased mortality, including psychotropics.

Depressive symptoms, physical activity, and clinical events: The ADAPT prospective pilot study.

BACKGROUND: Physical inactivity and depressive symptoms following cardiothoracic transplantation are recognized as potentially modifiable psychosocial factors to improve clinical outcomes. However, few studies have prospectively assessed these in ambulatory, outpatient transplant recipients. METHODS: We conducted a prospective, single-center study examining actigraphy-assessed physical activity (PA) levels over a 1-week period in heart or lung transplant recipients recruited at 6 months (range 4-9) post-transplant. Depressive symptoms (Centers for Epidemiologic Study of Depression [CESD]), quality of life (QoL), and clinical events (transplant-related hospitalization and death) were collected. Clustered Cox proportional hazards models were used to examine the associations between PA, psychological measures, and clinical events. RESULTS: Among 105 potentially eligible participants, 66 (63%) met inclusion criteria and were enrolled between July, 2016 and May, 2017, including 42 lung and 24 heart transplant recipients. The mean age of the population was 53 years, 41% were women and 18% were black. Participants tended to be sedentary, with the majority of activity spent within the "sedentary" level (61%) and an average daily step count of 7188 (SD = 2595). In addition, participants tended to exhibit subclinical depressive symptoms, (mean CESD = 9.4 [SD = 8]) with only a subset exhibiting levels suggestive of clinical depression (22%). Over a median follow-up of 1.4 years (1.14, 1.62), 21 participants (32%) experienced at least one transplant-related hospitalization, including two deaths. In adjusted survival models, greater intensity of PA (HR = 0.45 [0.24, 0.84] per 0.2 METs, P = .012) was associated with a lower risk of clinical events, whereas greater depressive symptoms (HR = 2.11 [1.58, 2.82] per 9 CESD points, P < .001) at 6 months were associated a higher likelihood of subsequent transplant-related hospitalization and/or death. CONCLUSIONS: Physical inactivity and depressive symptoms at 6 months post-transplant were predictive of subsequent adverse clinical events among ambulatory cardiothoracic transplant recipients. Future studies should examine whether improving these potentially modifiable post-transplant risk factors improves clinical outcomes.

Mortality and Medical Comorbidity in the Severely Mentally Ill.

BACKGROUND: Mentally ill patients die on average 10 years earlier than the general population, largely due to general medical disorders. This study is the first to explore in a large German sample the prevalence, mortality, and medical comorbidity in pa- tients with severe mental illness (SMI). The patients were affected by borderline personality disorder (BPD), psychotic disorders, bipolar disorder, or severe unipolar depression. METHODS: Our database consists of billing data from all adults with statutory health insurance in Germany. Twelve-month administrative SMI prevalence and medical comorbidity were estimated using cross-sectional data from 2016 (age ≥ 18; N = 59 561 310). Two-year mortality was established longitudinally in a randomly selected subset of the billing data (most recent mortality information available for 2012 to 2014; 2012: n = 15 590 107). RESULTS: Severe unipolar depression had the highest prevalence (2.01%), followed by psychotic disorders (1.25%), BPD (0.34%), and bipolar disorder (0.29%). While the prevalence of malignant neoplasms showed moderate deviations from reference values [severe unipolar depression: OR = 1.30 (95% CI = 1.29; 1.31), BPD: OR = 1.11 (1.09; 1.14), psychotic dis- orders: OR = 0.90 (0.89; 0.90), bipolar disorder: OR = 1.07 (1.06; 1.09)], other disease groups (infectious, endocrine/nutritional/ metabolic, circulatory, respiratory) were substantially elevated in all categories of SMI. Mortality rates for psychotic disorders, BPD, bipolar disorder, and severe unipolar depression were increased (OR = 2.38 [95% CI=2.32; 2.44], 2.30 [2.08; 2.54], 1.52 [1.42; 1.62], and 1.40 [1.37; 1.44], respectively), with a loss of 2.6 to 12.3 years, depending on age, sex, and SMI. CONCLUSION: Mortality is substantially elevated in all SMI patients. The results underline the need to remove barriers to adequate general medical care, both on the patient and the provider side, to reduce excess mortality.

The role of depression in unnatural death: A case-based retrospective study.

BACKGROUND: Depression affects the life of millions around the globe and perhaps also the manner of death. This study examined the role of depression in specific causes of unnatural death and whether alcohol and substance use affect this relationship, in one locality in Scotland. METHODS: The research used a retrospective case-based study approach to analyse 168 cases, quantifying data reported in mortuary files to allow for quantitative statistical analysis of associations and differences amongst the variables. RESULTS: A diagnosis of depression was associated with a higher likelihood of unnatural death due to suicide, drugs or homicide. A diagnosis of substance abuse was associated with a diagnosis of depression and with an increased likelihood of death due to suicide or drugs. A diagnosis of alcohol abuse was associated with a reduced likelihood of a diagnosis of depression but was associated with an increased likelihood of suicide. LIMITATIONS: This study relied on a small sample from one locality in Scotland which limited the ability to generalise the results and the retrospective case-based design also limited the potential for checking data accuracy or to consider temporal relationships, which limited the ability to interpret causality. CONCLUSIONS: This study found that there was a relationship between depression and unnatural death, which was mediated by alcohol and substance use. The importance of this study lies within the recognition of these relationships which identified the complexities of these relationships but suggested that some unnatural deaths within this population could be prevented.

Diagnosed Mental Health Conditions and Risk of Suicide Mortality.

OBJECTIVE: Although mental health conditions are risk factors for suicide, limited data are available on suicide mortality associated with specific mental health conditions in the U.S. population. This study aimed to fill this gap. METHODS: This study used a case-control design. Patients in the case group were those who died by suicide between 2000 and 2013 and who were patients in eight health care systems in the Mental Health Research Network (N=2,674). Each was matched with 100 general population patients from the same system (N=267,400). Diagnostic codes for five mental health conditions in the year before death were obtained from medical records: anxiety disorders, attention deficit-hyperactivity disorder (ADHD), bipolar disorder, depressive disorders, and schizophrenia spectrum disorder. RESULTS: Among patients in the case group, 51.3% had a recorded psychiatric diagnosis in the year before death, compared with 12.7% of control group patients. Risk of suicide mortality was highest among those with schizophrenia spectrum disorder, after adjustment for age and sociodemographic characteristics (adjusted odds ratio [AOR]=15.0) followed by bipolar disorder (AOR=13.2), depressive disorders (AOR=7.2), anxiety disorders (AOR=5.8), and ADHD (AOR=2.4). The risk of suicide death among those with a diagnosed bipolar disorder was higher in women than men. CONCLUSIONS: Half of those who died by suicide had at least one diagnosed mental health condition in the year before death, and most mental health conditions were associated with an increased risk of suicide. Findings suggest the importance of suicide screening and providing an approach to improve awareness of mental health conditions.

[The risk of medical comorbidity in mental disorders with a particular focus on depressive syndromes]. / Somatisches Krankheitsrisiko bei psychischen Erkrankungen unter besonderer Berücksichtigung depressiver Syndrome.

The risk of medical comorbidity in mental disorders with a particular focus on depressive syndromes Objectives: It has long been recognized that certain mental disorders, and in particular depressive syndromes, are associated with increased medical comorbidity. However, reliable data on the prevalence of comorbid medical diagnoses as well as the impact of these comorbidities on mortality are often rare and sometimes conflicting. Methods: A systematic literature review was conducted using PubMed and Google Scholar to provide a critical account of the current state of research on the comorbidities of medical and mental disorders, with a particular focus on depressive syndromes. Results: Among patients with mental disorders, all-cause mortality is about doubled as compared to the general population causing a significantly shortened life expectancy in the range of one to two decades. This excess mortality is primarily due to increased physical morbidity and mortality, and it cannot be excluded that, for patients with severe mental disorders, excess mortality has been increased over time. Depressive syndromes are often linked to a broad range of somatic symptoms and can be found in diseases, such as heart disease, stroke, diabetes mellitus, overweight/obesity, and asthma. Conclusion: Current studies provide ample evidence of close interactions between physical and mental health. Further developments in the field of psychosomatic medicine should take into consideration the health-related consequences of these interactions.

Statin treatment and the risk of depression.

BACKGROUND: The effect of statin treatment on the risk of developing depression remains unclear. Therefore, we assessed the association between statin treatment and depression in a nationwide register-based cohort study with up to 20 years of follow up. METHODS: We identified all statin users in the period from 1996 to 2013 among individuals born in Denmark between 1920 and 1983. One non-user was matched to each statin user based on age, sex and a propensity score taking several potential confounders into account. Using Cox regression we investigated the association between statin use and: (I) redemption of prescriptions for antidepressants, (II) redemption of prescriptions for any other drug, (III) depression diagnosed at psychiatric hospitals, (IV) cardiovascular mortality and (V) all-cause mortality. RESULTS: A total of 193,977 statin users and 193,977 non-users were followed for 2,621,282 person-years. Statin use was associated with (I) increased risk of antidepressant use (hazard rate ratio (HRR) = 1.33; 95% confidence interval (95%-CI) = 1.31-1.36), (II) increased risk of any other prescription drug use (HRR = 1.33; 95%-CI = 1.31-1.35), (III) increased risk of receiving a depression diagnosis (HRR = 1.22, 95%-CI = 1.12-1.32) - but not after adjusting for antidepressant use (HRR = 1.07, 95%-CI = 0.99-1.15), (IV) reduced cardiovascular mortality (HRR = 0.92, 95%-CI = 0.87-0.97) and (V) reduced all-cause mortality (HRR = 0.90, 95%-CI = 0.88-0.92). CONCLUSIONS: These results suggest that the association between statin treatment and antidepressant use is unspecific (equivalent association between statins and most other drugs) and that the association between statin use and depression diagnoses is mediated by residual confounding, bias or by downstream effects of the statin prescription (seeing a physician more often).