Cause of Death in Heart Failure Based on Etiology: Long-Term Cohort Study of All-Cause and Cardiovascular Mortality.

We assessed differences in long-term all-cause and cardiovascular (CV) mortality in heart failure (HF) outpatients based on the etiology of HF. Consecutive patients admitted to the HF Clinic from August 2001 to September 2019 (N = 2587) were considered for inclusion. HF etiology was divided into ischemic heart disease (IHD), dilated cardiomyopathy (DCM), hypertensive heart disease, alcoholic cardiomyopathy, drug-induced cardiomyopathy (DICM), valvular heart disease, and hypertrophic cardiomyopathy. All-cause death and CV death were the primary end points. Among 2387 patients included in the analysis (mean age 66.5 ± 12.5 years, 71.3% men), 1317 deaths were recorded (731 from CV cause) over a maximum follow-up of 18 years (median 4.1 years, interquartile range (IQR) 2-7.8). Considering IHD as the reference, only DCM had a lower risk of all-cause death (adjusted hazard ratio (aHR) 0.68, 95% confidence interval (CI) 0.56-0.83, p < 0.001), and only DICM had a higher risk of all-cause death (aHR 1.47, 95% CI 1.02-2.11, p = 0.04). However, almost all etiologies had a significantly lower risk of CV death than IHD. Among the studied HF etiologies, DCM and DICM have the lowest and highest risk of all-cause death, respectively, whereas IHD has the highest adjusted risk of CV death.

Association of serum interleukin-6 and C-reactive protein with depressive and adjustment disorders in COVID-19 inpatients.

BACKGROUND: Immune mechanisms are part of the pathophysiology of mental disorders, although their role remains controversial. In depressive disorders a chronic low-grade inflammatory process is observed, with higher interleukin-6 (IL-6) values. Furthermore, in SARS-CoV2 infection, which is closely related to depressive disorders, there is a proinflammatory cascade of cytokines that causes systemic inflammation. METHODS: The present study evaluates the relationship between IL-6 and C-reactive protein (CRP) serum levels and the presence of depressive and adjustment disorders in a sample of 1851 patients admitted to hospital for SARS-CoV2 infection from March to November 2020. Concentrations of IL-6 and CRP were determined within the first 72 â€‹h at admission and compared among groups of patients according to previous history and current presence of depression or adjustment disorders. RESULTS: IL-6 serum levels were significantly higher in the group of patients with depression and adjustment disorders compared to patients without such disorders (114.25 â€‹pg/mL (SD, 225.44) vs. 86.41 (SD, 202.97)), even after adjusting for several confounders. Similar results were obtained for CRP (103.94 â€‹mg/L (SD, 91.16) vs. 90.14 (SD, 85.73)). The absolute levels of IL-6 and CRP were higher than those of previous depression studies, and differences were only found for the subgroup of De Novo depressive or adjustment disorders. CONCLUSIONS: Serum concentrations of IL-6 and CRP are higher in COVID-19 patients with De Novo but not persistent depressive or adjustment disorders. Clinical features such as fatigue, asthenia, anhedonia, or anxiety can be the basis for this finding.

Head-to-head comparison of contemporary heart failure risk scores.

AIMS: Several heart failure (HF) web-based risk scores are currently used in clinical practice. Currently, we lack head-to-head comparison of the accuracy of risk scores. This study aimed to assess correlation and mortality prediction performance of Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score, which includes clinical variables + medications; Seattle Heart Failure Model (SHFM), which includes clinical variables + treatments + analytes; PARADIGM Risk of Events and Death in the Contemporary Treatment of Heart Failure (PREDICT-HF) and Barcelona Bio-Heart Failure (BCN-Bio-HF) risk calculator, which also include biomarkers, like N-terminal pro B-type natriuretic peptide (NT-proBNP). METHODS AND RESULTS: A total of 1166 consecutive patients with HF from different aetiologies that had NT-proBNP measurement at first visit were included. Discrimination for all-cause mortality was compared by Harrell's C-statistic from 1 to 5 years, when possible. Calibration was assessed by calibration plots and Hosmer-Lemeshow test and global performance by Nagelkerke's R2 . Correlation between scores was assessed by Spearman rank test. Correlation between the scores was relatively poor (rho value from 0.66 to 0.79). Discrimination analyses showed better results for 1-year mortality than for longer follow-up (SHFM 0.817, MAGGIC-HF 0.801, PREDICT-HF 0.799, BCN-Bio-HF 0.830). MAGGIC-HF showed the best calibration, BCN-Bio-HF overestimated risk while SHFM and PREDICT-HF underestimated it. BCN-Bio-HF provided the best discrimination and overall performance at every time-point. CONCLUSIONS: None of the contemporary risk scores examined showed a clear superiority over the rest. BCN-Bio-HF calculator provided the best discrimination and overall performance with overestimation of risk. MAGGIC-HF showed the best calibration, and SHFM and PREDICT-HF tended to underestimate risk. Regular updating and recalibration of online web calculators seems necessary to improve their accuracy as HF management evolves at unprecedented pace.

Mental disorders, psychopharmacological treatments, and mortality in 2150 COVID-19 Spanish inpatients.

OBJECTIVE: To determine how mental disorders and psychopharmacological treatments before and during COVID-19 hospital admissions are related to mortality. METHODS: Subjects included in the study were all adult patients with a diagnosis of COVID-19, confirmed clinically and by PCR, who were admitted to a tertiary university hospital in Badalona (Spain) between March 1 and November 17, 2020. Data were extracted anonymously from computerized clinical records. RESULTS: 2,150 subjects were included, 57% males, mean age 61 years. History of mental disorders was registered in 957 (45%). Throughout admission, de novo diagnosis of mood or anxiety, stress, or adjustment disorder was made in 12% of patients without previous history. Delirium was diagnosed in 10% of cases. 1011 patients (47%) received a psychotropic prescription during admission (36% benzodiazepines, 22% antidepressants, and 21% antipsychotics). Mortality rate was 17%. Delirium during admission and history of mood disorder were independently associated with higher mortality risk (hazard ratios, 1.39 and 1.52 respectively), while previous year's treatments with anxiolytics/hypnotics and antidepressants were independently associated with lower mortality risk (hazard ratios, 0.47 and 0.43, respectively). CONCLUSION: Mental symptoms are very common in patients hospitalized for COVID-19 infection. Detecting, diagnosing, and treating them is key to determining the prognosis of the disease and functional recovery.

Mortality trends in an ambulatory multidisciplinary heart failure unit from 2001 to 2018.

To assess mortality trends at 1 and 3 years from 2001 to 2018 in a real-life cohort of HF outpatients from different etiologies with depressed and preserved LVEF. A total of 2368 consecutive patients with HF (mean age 66.4 ± 12.9 years, 71% men, 15.4% with preserved LVEF) admitted to a HF clinic from August 2001 to September 2018 were included in the study. Patients were divided into five quintiles (Q) according to the period of admission. Trends for all-cause and cardiovascular mortality from Q1 to Q5 were assessed by linear regression. Patients with LVEF < 50% had a progressive decrease in the rates of all-cause and cardiovascular death at 1 year (12.1% in Q1 to 6.5% in Q5, p = 0.003; and 8.4% in Q1 to 3.8% in Q5, p = 0.007, respectively) and 3 years (30.5% in Q1 to 17.0% in Q5, p = 0.003; and 23.9% in Q1 to 9.8% in Q5, p = 0.003, respectively). These trends remained significant after adjusting for clinical characteristics and risk. No significant trend in mortality was observed in patients with LVEF ≥ 50%. In a cohort of real-life ambulatory patients with HF, mortality progressively declined in patients with LVEF < 50%, but the same trend was not observed in patients with preserved LVEF.

Patient Health Questionnaire-9 scores do not accurately estimate depression prevalence: individual participant data meta-analysis.

OBJECTIVES: Depression symptom questionnaires are not for diagnostic classification. Patient Health Questionnaire-9 (PHQ-9) scores ≥10 are nonetheless often used to estimate depression prevalence. We compared PHQ-9 ≥10 prevalence to Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) major depression prevalence and assessed whether an alternative PHQ-9 cutoff could more accurately estimate prevalence. STUDY DESIGN AND SETTING: Individual participant data meta-analysis of datasets comparing PHQ-9 scores to SCID major depression status. RESULTS: A total of 9,242 participants (1,389 SCID major depression cases) from 44 primary studies were included. Pooled PHQ-9 ≥10 prevalence was 24.6% (95% confidence interval [CI]: 20.8%, 28.9%); pooled SCID major depression prevalence was 12.1% (95% CI: 9.6%, 15.2%); and pooled difference was 11.9% (95% CI: 9.3%, 14.6%). The mean study-level PHQ-9 ≥10 to SCID-based prevalence ratio was 2.5 times. PHQ-9 ≥14 and the PHQ-9 diagnostic algorithm provided prevalence closest to SCID major depression prevalence, but study-level prevalence differed from SCID-based prevalence by an average absolute difference of 4.8% for PHQ-9 ≥14 (95% prediction interval: -13.6%, 14.5%) and 5.6% for the PHQ-9 diagnostic algorithm (95% prediction interval: -16.4%, 15.0%). CONCLUSION: PHQ-9 ≥10 substantially overestimates depression prevalence. There is too much heterogeneity to correct statistically in individual studies.

Trends in modes of death in heart failure over the last two decades: less sudden death but cancer deaths on the rise.

AIMS: Better management of heart failure (HF) over the past two decades has improved survival, mainly by reducing the incidence of death due to cardiovascular (CV) causes. Deaths due to non-CV causes, particularly cancer, may be increasing. This study explored the modes of death of consecutive patients who attended a HF clinic over 17 years. METHODS AND RESULTS: A total of 935 deaths were ascertained from 2002 to 2018 among 1876 patients (mean age 65.8 ± 12.5 years, 75% men, left ventricular ejection fraction < 50%) admitted to our HF clinic. Median follow-up was 4.2 years [1.9-7.8]. Mode of death was curated from patient health records and verified by the Catalan and Spanish health system databases. Trends for every mode of death were assessed by polynomial regression. Two trends were observed: a significant reduction in sudden death (P = 0.03) without changes in HF progression as mode of death (P = 0.26), and a significant increase in non-CV modes of death (P < 0.001). Non-CV deaths accounted for 17.4% of deaths in 2002 and 65.8% of deaths in 2018. A total 138 deaths were due to cancer (37% of non-CV deaths). A significant trend was observed towards a progressive increase in cancer deaths over time (P = 0.002). The main mode of cancer mortality was lung cancer. CONCLUSIONS: The modes of death in HF have shifted over the last two decades. Patients with HF die less due to sudden death and more due to non-CV causes, mainly cancer. Whether HF triggers cancer, or cancer develops in HF survivors, deserves further insight.

A bio-clinical approach for prediction of sudden cardiac death in outpatients with heart failure: The ST2-SCD score.

BACKGROUND: Sudden cardiac death (SCD) is one of the main modes of death in heart failure (HF) patients and its prediction remains a real challenge. Our aim was to assess the incidence of SCD at 5 years HF contemporary managed outpatients, and to find a simple prediction model for SCD. METHODS: SCD was considered any unexpected death, witnessed or not, occurring in a previously stable patient with no evidence of worsening HF or any other cause of death. A competing risk strategy was adopted using the Fine-Gray method of Cox regressions analyses that considered other causes of death as the competing event. RESULTS: The derivation cohort included 744 consecutive outpatients (72% men, age 67.9 ±â€¯12.2 years, left ventricular ejection fraction [LVEF] 36% ±â€¯14). During follow-up, 312 deaths occurred, 40 SCDs (5.4%). Age, haemoglobin, eGFR, HF duration, high-sensitivity troponin T, NTproBNP, and ST2 were associated with SCD in univariate analyses; HF duration (p = 0.006), eGFR (p < 0.001), LVEF <45% (p = 0.03), and ST2 (p = 0.006) remained in multivariable analysis. A predictive score (ST2-SCD) including dichotomous variables (ST2 > 45, LVEF <45%, HF duration >3 years, eGFR < 55, age ≥ 60 years and male sex) provided a Harrell's C-statistic of 0.82 (0.76-0.89)), reaching 0.87 (0.80-0.95) in the validation cohort (n = 149). CONCLUSIONS: In contemporary managed HF, SCD occurred in 5.4% of outpatients, accounting for 12.8% of all deaths at 5 years. Of the 3 studied biomarkers, only ST2 remained independently associated with SCD. A model containing age, sex, ST2, eGFR, LVEF, and HF duration reasonably predicted 5-years risk of SCD.

Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study.

OBJECTIVE: To assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment. METHODS: We recruited HIV-infected patients with cognitive impairment on stable antiretroviral therapy in a randomized controlled pilot trial with a 48-week follow-up. An additional assessment was held at 12 weeks. Participants received transdermal rivastigmine (9.5 mg daily), lithium (400 mg twice daily, titrated progressively), or remained in a control group (no new medication). The primary efficacy endpoint was change in a global cognitive score (NPZ-7). Secondary endpoints included change in specific cognitive measures, domains, and functional parameters. Safety covered the frequency of adverse events and changes in laboratory results. RESULTS: Seventy-six subjects were screened, and 29 were finally enrolled. Better cognitive outcomes were observed in all groups, although there were no significant differences between the arms (mean NPZ-7 change [SD]): rivastigmine, 0.35 (0.14); lithium, 0.25 (0.40); control, 0.20 (0.44) (p = 0.78). The rivastigmine group showed the highest positive trend (mean NPZ-7 [SD], baseline vs week 48): rivastigmine, -0.47 (0.22) vs -0.11 (0.29), p = 0.06; lithium, -0.50 (0.40) vs -0.26 (0.21), p = 0.22; control, -0.52 (0.34) vs -0.32 (0.52), p = 0.44. The cognitive domains with the highest positive trends were information processing speed at week 12 and executive function at week 48 (rivastigmine vs control): information processing speed, 0.35 (0.64) vs -0.13 (0.25), p = 0.17, d = 0.96; and executive functioning, 0.73 (0.33) vs 0.03 (0.74), p = 0.09, d = 1.18. No relevant changes were observed regarding functional outcomes. A total of 12 (41%) individuals dropped out of the study: 2 (20%) were due to medication-related effects in the rivastigmine group and 4 (36%) in the lithium group. No severe adverse events were reported. CONCLUSIONS: The results from this small randomized trial indicate that transdermal rivastigmine did not provide significant cognitive benefits in people with HAND on stable antiretroviral therapy, even though positive trends were found in specific cognitive domains. Relevant tolerability issues were not observed.

Depression as Measured by PHQ-9 Versus Clinical Diagnosis as an Independent Predictor of Long-Term Mortality in a Prospective Cohort of Medical Inpatients.

BACKGROUND: Depression has been associated with higher rates of mortality in medical patients. The aim of the study was to evaluate the impact of depression in medical inpatients on the rate of mortality during a prolonged follow-up period. METHOD: This is a prospective follow-up study of a cohort of medical inpatients assessed during 1997-1998 in medical and surgical units at a tertiary university hospital in Spain and followed-up for a period ranging between 16.5 and 18 years. Eight hundred three patients were included; 420 (52.3%) were male, and the mean (SD) age was 41.7 (13.8) years. Main outcome was death for any cause during follow-up. The original full Patient Health Questionnaire (PHQ) was administered at baseline as self-report from which the PHQ-9 was derived. Depressive disorders were assessed using PHQ-9 and a structured clinical interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition). RESULTS: Depressive disorders as defined by PHQ-9 were detected in 206 patients (25.7%), 122 (15.2%) of them fulfilling criteria for major depression. During follow-up, 152 patients (18.9%) died. A PHQ score indicating the presence of major depressive disorder predicted increased mortality (hazard ratio [HR], 2.44; 95% CI, 1.39-4.29), even after adjusting for important demographic and clinical variables. Similarly, the PHQ-9 score as a continuous measure of depression severity predicted increased mortality (HR, 1.06; 95% CI, 1.02-1.10). Results were similar for clinical interview diagnoses of major depression (HR, 2.07; 95% CI, 1.04-4.09). CONCLUSIONS: Medical inpatients with a PHQ depressive disorder had a nearly 2-fold higher risk of long-term mortality, even after adjustment for several confounders. Depression severity as represented by the PHQ-9 score was also a risk factor.

Mental disorders in HIV/HCV coinfected patients under antiviral treatment for hepatitis C.

This paper aims to review the epidemiology and management of mental disorders in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, the need for antiviral therapy in this specific population, and current treatment strategies for HIV/HCV patients with psychiatric and/or substance use disorders. This is a narrative review. Data was sourced from electronic databases and was not limited by language or date of publication. HIV infection has become a survivable chronic illness. Prevalence of HCV infection among HIV-infected patients is high ranging from 50% to 90%. Patients with psychiatric diseases have also an increased risk for HIV/HCV coinfection. The most effective strategy to decrease HCV-related morbidity and mortality in coinfection is to achieve viral eradication. Although psychiatric symptoms often appear during antiviral treatment and may be associated with the use of interferon-alpha (IFN-α), recent evidence suggests that many patients with comorbid mental and substance use disorders can be treated safely. Recent data indicate that IFNα-induced psychiatric side effects have a similar prevalence in HIV/HCV coinfected patients than in monoinfected patients and they can be managed and even prevented successfully with psychopharmacological strategies in the frame of a multidisciplinary team. New antivirals offer INF-free therapies for this specific population.

Weight Loss in Obese Patients With Heart Failure.

BACKGROUND: In heart failure (HF), weight loss (WL) has been associated with an adverse prognosis whereas obesity has been linked to lower mortality (the obesity paradox). The impact of WL in obese patients with HF is incompletely understood. Our objective was to explore the prevalence of WL and its impact on long-term mortality, with an emphasis on obese patients, in a cohort of patients with chronic HF. METHODS AND RESULTS: Weight at first visit and the 1-year follow-up and vital status after 3 years were assessed in 1000 consecutive ambulatory, chronic HF patients (72.7% men; mean age 65.8±12.1 years). Significant WL was defined as a loss of ≥5% weight between baseline and 1 year. Obesity was defined as body mass index ≥30 kg/m(2) (N=272). Of the 1000 patients included, 170 experienced significant WL during the first year of follow-up. Mortality was significantly higher in patients with significant WL (27.6% versus 15.3%, P<0.001). In univariable Cox regression analysis, patients with significant WL had 2-fold higher mortality (hazard ratio 1.95 [95% CI 1.39-2.72], P<0.001). In multivariable analysis, adjusting for age, sex, body mass index, New York Heart Association functional class, left ventricular ejection fraction, HF duration, ischemic etiology, diabetes, and treatment, significant WL remained independently associated with higher mortality (hazard ratio 1.89 [95% CI 1.32-2.68], P<0.001). Among obese patients with HF, significant WL was associated with an even more ominous prognosis (adjusted hazard ratio for death of 2.38 [95% CI 1.31-4.32], P=0.004) than that observed in nonobese patients (adjusted hazard ratio 1.83 [95% CI 1.16-2.89], P=0.01). CONCLUSIONS: Weight loss ≥5% in patients with chronic HF was associated with high long-term mortality, particularly among obese patients with HF.

Aging and Heart Rate in Heart Failure: Clinical Implications for Long-term Mortality.

OBJECTIVE: To assess the relationship between resting heart rate and long-term all-cause mortality in ambulatory patients with heart failure (HF) relative to age, considering that although heart rate has been strongly associated with mortality in HF, the influence of age on target heart rate is incompletely characterized. PATIENTS AND METHODS: Consecutive patients in sinus rhythm referred to an ambulatory HF clinic of a university hospital between August 1, 2001, and March 31, 2012, were included. Unadjusted and adjusted Cox regression analyses were performed to assess heart rate as a prognostic marker, both as a continuous variable and after categorization into quintiles. Smooth spline estimates and hazard ratios (HRs) were plotted for 2 age strata (<75 years vs ≥75 years) for each individual heart rate. RESULTS: A total of 1033 patients were included (766 men [74.2%]; mean age, 65.1±12.6 years). During a mean follow-up of 4.6±3.3 years (median, 3.8 years [25th-75th percentile, 1.9-6.9]), 476 patients (46.1%) died. Mortality was associated with a statistically greater heart rate in the total cohort (HR, 1.18; 95% CI, 1.11-1.26; P<.001). From a clinical viewpoint, this means an 18% increased risk for every 10-beats/min elevation in heart rate. The same characteristics were present in the relationship between heart rate assessed after 6 months and long-term mortality (HR, 1.30; 95% CI, 1.20-1.42; P<.001). Overall, the prognostic importance of heart rate in ambulatory patients with HF was largely influenced by patient age. Remarkably, in the elderly population (≥75 years), heart rate below 68 beats/min conferred an increased risk of death, whereas in younger patients, mortality exhibited a declining slope at even the lowest heart rates. CONCLUSION: Our research, if applicable to the prospective management of patients with ambulatory HF, suggests that patients aged 75 years or older have the best outcomes with target heart rates of 68 beats/min; however, younger patients may benefit from lower heart rates, even below 55 beats/min.

Unified Protocol for psychiatric and psychological assessment of candidates for transplantation of organs and tissues, PSI-CAT.

INTRODUCTION: Transplantation is the treatment option that offers improved survival and quality of life as compared to organ failure. Psychiatric and psychological aspects of transplant candidates are important, especially in the pre-assessment stage, as the influence of these factors can hinder post-surgical outcome in both the implanted organ survival and the quality of life of the transplanted person. Of particular importance, are the factors related to pathology due to substance use, psychopathology, and psychosocial support. There are currently few guidelines on the correct evaluation of patients eligible for these complex procedures. METHOD: Nineteen psychiatrists and clinical psychologists from six public hospitals in Catalonia conducted a systematic consensus to determine the design of a Unified Protocol psychological and psychiatric evaluation. An annual work plan was implemented, during which; the objectives were defined, a literature review was conducted, the inclusion and exclusion criteria were discussed, questionnaires were selected, and a structured interview was developed. RESULTS: With the implementation of the work plan, the Assessment Protocol presented in this article was designed. CONCLUSIONS: systematic work and improving cooperation between psychiatrists and clinical psychologists, has led to homogeneity and consensus on a unified evaluation protocol.

Management of mental health problems prior to and during treatment of hepatitis C virus infection in patients with drug addiction.

Psychiatric comorbidity is a common problem in patients with substance use disorders. Patients with psychiatric diseases and/or substance abuse have an increased risk for hepatitis C virus (HCV) infection. Furthermore, psychiatric problems occur frequently during antiviral treatment and may be associated with the use of interferon alpha (IFN-α) but also with the primary psychiatric condition. As a consequence, substance abuse and/or acute psychiatric problems are still important reasons for nontreatment of chronic HCV infection. However, prospective and controlled data from recent years showed that if an interdisciplinary treatment is provided, patients with substance use disorders and/or psychiatric diseases do not differ regarding sustained virologic response or IFN-α-associated complications such as depression when compared with controls. Moreover, depression as the most important acute IFN-α-associated psychiatric adverse event can be acutely treated or even prevented by antidepressant pretreatment. Other, more rare but severe complications such as mania, psychotic symptoms, or delirium need individual psychiatric interventions.

Depression, antidepressants, and long-term mortality in heart failure.

BACKGROUND: This study was designed to assess whether depression and the use of antidepressants were related to long-term mortality in heart failure. METHODS: Heart failure outpatients (n=1017) from a specialized tertiary unit in Spain were prospectively studied for a median follow-up of 5.4 years (IQR 3.1-8.1). Depressive symptoms were assessed using an abbreviated version of the geriatric depression scale. Survival rates during the study period (August 2001 until December 2010) and hazard ratios (HR) for mortality were adjusted by several demographic and clinical variables. RESULTS: Depressive symptoms were detected in 302 patients (29.7%) at baseline and 222 (21.8%) de novo during follow-up; 304 patients (29.9%) received at least one prescription of antidepressants, mainly selective serotonin reuptake inhibitors (92.8%); 441 patients (43.4%) died. In a multivariate Cox proportional hazard model, depression was associated with an increased all-cause (HR, 1.39; 95% CI, 1.15-1.68), but not cardiovascular, mortality risk after adjustment for several demographic and clinical confounders. The use of any antidepressant was not independently associated with mortality (HR, 0.89; 95% CI, 0.71-1.13), but benzodiazepines showed a protective role (HR, 0.70; 95% CI, 0.57-0.87). On the contrary, fluoxetine prescriptions, but not duration of fluoxetine treatment, were associated with increased mortality (HR, 1.66; 95% CI, 1.13-2.44). CONCLUSIONS: Depressive symptoms are associated with long-term mortality, but the use of antidepressants and benzodiazepines is safe regarding survival in HF patients, although further research is needed considering individual antidepressants separately.

Hepatitis C infection, antiviral treatment and mental health: a European expert consensus statement.

Mental health problems frequently occur in chronic infection with the hepatitis C virus (HCV) and during antiviral treatment with pegylated interferon-alpha (PegIFNα) and ribavirin. Depression is one of the most important complications during antiviral treatment of chronic hepatitis C infection. However, an increased prevalence of depression, fatigue, and cognitive disturbances has also been reported in untreated HCV-positive patients. Patients with psychiatric disorders or drug addiction also have an increased risk of HCV infection. Furthermore, because of possible drug-drug interactions, new antivirals administered together with PegIFNα and ribavirin may complicate psychiatric side effect management, even if no specific psychiatric adverse events are known so far for these new drugs. The European liver patient's organization (ELPA) organised a European expert conference to review the literature and develop expert recommendations for the management of mental health problems in HCV infected patients. This paper results from the output of the 2011 EASL meeting and subsequent dialogue with patient groups and relevant experts in Europe. It summarises the current knowledge of HCV infection and the brain; prevalence, course, and neurobiology of IFN-α associated psychiatric side effects; possible risk factors for IFN-α associated depression and suicide attempts; psychiatric management of HCV infected patients before and during antiviral treatment; prevention of IFN- α associated psychiatric side effects; and psychiatric aspects of the new antivirals. The summarised current knowledge about mental health changes before and during antiviral treatment should improve interdisciplinary management of HCV infected patients.

Prophylactic treatment with escitalopram of pegylated interferon alfa-2a-induced depression in hepatitis C: a 12-week, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Depression is one of the main reasons for treatment withdrawal and failure in chronic hepatitis C patients treated with interferon. Antidepressants are useful for its treatment, but whether they can also be used for prevention has yet to be established. METHOD: To evaluate the efficacy and safety of escitalopram for preventing interferon alfa-2a-induced depression, we conducted an investigator-initiated multicenter, randomized, double-blind, placebo-controlled trial in 133 chronic hepatitis C patients without baseline mental disorders who were randomly assigned to receive escitalopram or placebo during the first 12 weeks of treatment. Primary efficacy outcomes were the development of DSM-IV major depression and scores on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hospital Anxiety and Depression Scale (HADS). Primary safety end points were biochemical and virological responses. Patients were recruited between March 2005 and July 2006. RESULTS: Rates of major depression were low (5.4%) and did not differ between placebo (3.2%) and escitalopram (7.6%). MADRS and HADS scores significantly increased during treatment (P < .001 and P = .028, respectively), but there were no differences between treatment groups. Sustained virological response was achieved by 69.2% of patients, 70.4% in the placebo group and 67.9% in the escitalopram group. CONCLUSIONS: Findings do not support the use of an antidepressant to prevent interferon-induced depression during the first 12 weeks of treatment in chronic hepatitis C patients at low psychiatric risk. Future studies should be directed to subpopulations of patients at high psychiatric risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00166296.