Jeff C. Huffman

Depression and Cardiac Disease A Review

Depression is highly prevalent in cardiac patients, with 20% to 40% of patients meeting criteria for major depressive disorder or experiencing an elevation in depressive symptoms. These depressive symptoms are often chronic and persistent, and they have been associated with the development and progression of coronary artery disease, worse health-related quality of life, poor physical functioning, recurrent cardiac events, and a 2- to 2.5-fold increased risk of mortality. Impaired adherence to health behaviors and adverse physiological effects of depression, including inflammation, endothelial dysfunction, platelet hyperactivity, and autonomic nervous system abnormalities, may link depression with adverse cardiac outcomes. Pharmacologic and psychotherapeutic interventions appear to be safe and effective at reducing depressive symptoms in patients with cardiovascular disease and may impact cardiac outcomes. Unfortunately, depression often is unrecognized and untreated in this population, despite the availability of brief screening tools that can be used for this purpose. We recommend the routine screening of cardiac patients for depression when there are adequate mechanisms for management and referral, such as available consulting psychiatrists or care management programs that facilitate the delivery of pharmacologic and psychotherapeutic treatments in this vulnerable population.

QTc Prolongation, Torsades de Pointes, and Psychotropic Medications

BACKGROUND Prolongation of the corrected QT (QTc) interval is a key issue for patients who receive psychotropic medications. Such patients may have baseline clinical risk factors for QTc prolongation, and many psychotropic medications may further prolong this interval. This has great clinical relevance, as QTc prolongation is linked with dangerous arrhythmias, especially torsades de pointes (TdP). METHODS We summarize current literature regarding appropriate methods of calculating the QTc interval, the association of the QTc interval with TdP, and risk factors for QTc prolongation. We then review connections between psychiatric medications and QTc prolongation, with a specific focus on antidepressants and antipsychotics. RESULTS QTc interval prolongation is an established, though imperfect, risk marker for TdP. There are no well-controlled studies that assess the risk of TdP associated with psychotropic agents. There are limited data that selective serotonin reuptake inhibitors (SSRIs) as a class are linked to QTc prolongation; citalopram appears more likely than others to induce this phenomenon. Among antipsychotics, thioridazine remains the agent most associated with QTc prolongation; intravenous haloperidol also appears to carry an increased risk. Of the atypical antipsychotics, ziprasidone appears most likely to prolong the QTc interval. CONCLUSIONS The majority of patients in need of psychotropic medications display few risk factors for QTc prolongation and should be considered to be at low risk for TdP. The frequency of cardiac monitoring for patients receiving psychiatric medications should be individually determined, based on the prescribed agent(s) and additional risk factors for TdP.

Collaborative Care for Depression and Anxiety Disorders in Patients With Recent Cardiac Events The Management of Sadness and Anxiety in Cardiology (MOSAIC) Randomized Clinical Trial

IMPORTANCE Depression and anxiety are associated with adverse cardiovascular outcomes in patients with recent acute cardiac events. There has been minimal study of collaborative care (CC) management models for mental health disorders in high-risk cardiac inpatients, and no prior CC intervention has simultaneously managed depression and anxiety disorders. OBJECTIVE To determine the impact of a low-intensity CC intervention for depression, generalized anxiety disorder, and panic disorder among patients hospitalized for an acute cardiac illness. DESIGN, SETTING, AND PARTICIPANTS Single-blind randomized clinical trial, with study assessors blind to group assignment, from September 2010 through July 2013 of 183 patients admitted to inpatient cardiac units in an urban academic general hospital for acute coronary syndrome, arrhythmia, or heart failure and found to have clinical depression, generalized anxiety disorder, or panic disorder on structured assessment. INTERVENTIONS Participants were randomized to 24 weeks of a low-intensity telephone-based multicomponent CC intervention targeting depression and anxiety disorders (n = 92) or to enhanced usual care (serial notification of primary medical providers; n = 91). The CC intervention used a social work care manager to coordinate assessment and stepped care of psychiatric conditions and to provide support and therapeutic interventions as appropriate. MAIN OUTCOMES AND MEASURES Improvement in mental health-related quality of life (Short Form-12 Mental Component Score [SF-12 MCS]) at 24 weeks, compared between groups using a random-effects model in an intent-to-treat analysis. RESULTS Patients randomized to CC had significantly greater estimated mean improvements in SF-12 MCS at 24 weeks (11.21 points [from 34.21 to 45.42] in the CC group vs 5.53 points [from 36.30 to 41.83] in the control group; estimated mean difference, 5.68 points [95% CI, 2.14-9.22]; P = .002; effect size, 0.61). Patients receiving CC also had significant improvements in depressive symptoms and general functioning, and higher rates of treatment of a mental health disorder; anxiety scores, rates of disorder response, and adherence did not differ between groups. CONCLUSIONS AND RELEVANCE A novel telephone-based, low-intensity model to concurrently manage cardiac patients with depression and/or anxiety disorders was effective for improving mental health-related quality of life in a 24-week trial. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01201967.

Effects of Depression and Anxiety Improvement on Adherence to Medication and Health Behaviors in Recently Hospitalized Cardiac Patients

Impaired adherence to medications and health behaviors may mediate the connection between psychiatric symptoms and mortality in cardiac patients. This study assessed the association between improvements in depression/anxiety and self-reported adherence to health behaviors in depressed cardiac patients in the 6 months after cardiac hospitalization. Data were analyzed from depressed patients on inpatient cardiac units who were hospitalized for acute coronary syndrome, heart failure, or arrhythmia and enrolled in a randomized trial of collaborative care depression management (n = 134 in primary analysis). Measurements of depression (Patient Health Questionnaire-9), anxiety (Hospital Anxiety and Depression Scale, Anxiety subscale), and adherence to secondary prevention behaviors (Medical Outcomes Study-Specific Adherence Scale items) were obtained at baseline, 6 weeks 12 weeks, and 6 months. The association between improvement in depression/anxiety and adherence was assessed by linear regression after accounting for the effects of multiple relevant covariates. At all time points improvement in the Patient Health Questionnaire-9 was significantly and independently associated with self-reported adherence to medications and secondary prevention behaviors. In contrast, improvement in the Hospital Anxiety and Depression Scale, Anxiety subscale was associated with improved adherence only at 6 weeks. In conclusion, in a cohort of depressed cardiac patients, improvement in depression was consistently and independently associated with superior self-reported adherence to medications and secondary prevention behaviors across a 6-month span, whereas improvement in anxiety was not.

Meta-Analysis of Selective Serotonin Reuptake Inhibitor–Associated QTc Prolongation

OBJECTIVE To evaluate the association between selective serotonin reuptake inhibitors (SSRIs) and corrected QT interval (QTc) prolongation via meta-analysis of prospective studies. DATA SOURCES PubMed/MEDLINE database (January 1, 1975-August 15, 2012), with additional reports identified using hand searches of reference lists of relevant articles. Key words searched were QT, torsades de pointes, and sudden cardiac death, combined with antidepressants, citalopram, escitalopram, fluoxetine, sertraline, paroxetine, and fluvoxamine. English-, Spanish-, and German-language articles were included. STUDY SELECTION Two reviewers independently identified prospective controlled studies in adults that reported data related to QTc intervals prior to and following treatment with SSRIs. DATA EXTRACTION AND SYNTHESIS Three reviewers independently extracted study-level data including population characteristics, method of QTc measurement and treatment and outcome data. Two independent reviewers critiqued study quality. Publication bias was assessed visually using a funnel plot and quantitatively. Heterogeneity was measured using Cochran Q statistic. RESULTS Sixteen articles (with 25 distinct data subsets) involving 4,292 patients were included. SSRIs were associated with a dose-dependent increase in QTc interval compared to placebo (+6.10 milliseconds; 95% CI, 3.47-8.73; P < .001). Tricyclic antidepressants (TCAs) were associated with a significantly greater QTc increase than SSRIs (TCA prolongation, 7.05 milliseconds; 95% CI, 3.84-10.27 greater than SSRIs; P < .001). With respect to specific SSRI agents, citalopram was associated with significantly greater QTc prolongation than sertraline, paroxetine, and fluvoxamine. CONCLUSIONS SSRIs were associated with a modest but statistically significant increase in the QTc interval, although to a lesser extent than TCAs; this finding was not limited to any single study. Citalopram was associated with more QTc prolongation than most other SSRIs.

The relationship between depression, anxiety, and cardiovascular outcomes in patients with acute coronary syndromes

Depression and anxiety occur at high rates among patients suffering an acute coronary syndrome (ACS). Both depressive symptoms and anxiety appear to adversely affect in-hospital and long term cardiac outcomes of post-ACS patients, independent of traditional risk factors. Despite their high prevalence and serious impact, mood and anxiety symptoms go unrecognized and untreated in most ACS patients and such symptoms (rather than being transient reactions to ACS) persist for months and beyond. The mechanisms by which depression and anxiety are linked to these negative medical outcomes are likely a combination of the effects of these conditions on inflammation, catecholamines, heart rate variability, and endothelial function, along with effects on health-promoting behavior. Fortunately, standard treatments for these disorders appear to be safe, well-tolerated and efficacious in this population; indeed, selective serotonin reuptake inhibitors may actually improve cardiac outcomes. Future research goals include gaining a better understanding of the combined effects of depression and anxiety, as well as definitive prospective studies of the impact of treatment on cardiac outcomes. Clinically, protocols that allow for efficient and systematic screening, evaluation, and treatment for depression and anxiety in cardiac patients are critical to help patients avoid the devastating effects of these illnesses on quality of life and cardiac health.

Positive psychological attributes and cardiac outcomes: associations, mechanisms, and interventions.

BACKGROUND Intervention research at the intersection of psychiatry and cardiology has primarily focused on the relationship between negative psychological syndromes (e.g., depression) and cardiac outcomes, with less emphasis on positive psychological attributes, such as optimism, gratitude, and well-being, as they relate to cardiac disease. METHODS Literature is reviewed in three specific areas regarding positive attributes and cardiac disease: (1) associations between positive attributes and cardiac outcomes, (2) potential mechanisms-both behavioral and physiologic-by which positive psychological states may impact cardiovascular health, and (3) interventions aimed at cultivating positive psychological attributes in healthy and medically ill persons. RESULTS There is significant evidence that positive psychological attributes--especially optimism--may be independently associated with superior cardiac outcomes. Positive attributes appear to be associated with increased participation in cardiac health behaviors (e.g., healthy eating, physical activity) linked to beneficial outcomes; data linking positive psychological states and biomarkers of cardiac health (e.g., inflammatory markers) is mixed but suggests a potential association. Positive psychological interventions have consistently been associated with improved well-being and reduced depressive symptoms, though there have been few such studies in the medically ill. CONCLUSIONS These findings regarding the relationship between positive psychological attributes and cardiac health are promising and suggest that positive psychology interventions may be worth study in this population. However, questions remain about the strength and specificity of these relationships, the most salient positive psychological attributes, and the impact of positive psychological interventions on health outcomes in cardiac patients.

The impact of mental illness on cardiac outcomes: A review for the cardiologist

Traditional cardiac risk factors, such as smoking, hypertension and obesity, are widely accepted contributors to the onset and progression of cardiovascular disease (CVD), one of the foremost causes of morbidity and mortality worldwide. Largely overlooked, however, is the impact of mental health on cardiac disease. From extensive MEDLINE and PsycINFO searches, we have reviewed the association between specific psychiatric disorders and CVD-related morbidity and mortality, the efficacy and safety of their treatments, and plausible behavioral and biological mechanism through which these associations may occur. The preponderance of evidence suggests that depression, anxiety disorders, bipolar disorder and schizophrenia are all important cardiac risk factors, and patients with these disorders are at significantly higher risk for cardiac morbidity and mortality than are their counterparts in the general population. Antidepressants, antipsychotics, mood stabilizers and benzodiazepines are effective therapeutic interventions, and many are safe to use in cardiac populations. Some, such as selective serotonin reuptake inhibitors and atypical antipsychotics, may even improve cardiac outcomes in healthy individuals and patients with CVD, although more work is needed to confirm this hypothesis. A combination of behavioral and biological mechanisms underlies the association between cardiac disease and mental illness, many of which are shared across disorders. With further research, it may be learned that psychiatric treatments definitively reverse the detrimental effects of mental illness on cardiac health. Currently, however, the challenge lies in raising awareness of mental health issues in cardiac patients, so that basic but critical treatments may be initiated in this population.

Development of a positive psychology intervention for patients with acute cardiovascular disease

The management of depression and other negative psychological states in cardiac patients has been a focus of multiple treatment trials, though such trials have not led to substantial improvements in cardiac outcomes. In contrast, there has been minimal focus on interventions to increase positive psychological states in cardiac patients, despite the fact that optimism and other positive states have been associated with superior cardiovascular outcomes. Our objective was to develop an 8-week, phone-based positive psychology intervention for patients hospitalized with acute cardiac disease (acute coronary syndrome or decompensated heart failure). Such an intervention would consist of positive psychology exercises adapted for this specific population, and it would need to be feasible for practitioners and patients in real-world settings. By adapting exercises that were previously validated in healthy individuals, we were able to generate a positive psychology telemedicine intervention for cardiac patients that focused on optimism, kindness, and gratitude. In addition, we successfully created a companion treatment manual for subjects to enhance the educational aspects of the intervention and facilitate completion of exercises. Finally, we successfully performed a small pilot trial of this intervention, and found that the positive psychology intervention appeared to be feasible and well-accepted in a cohort of patients with acute cardiac illness. Future studies should further develop this promising intervention and examine its impact on psychological and medical outcomes in this vulnerable population of cardiac patients.

Essential articles on collaborative care models for the treatment of psychiatric disorders in medical settings: a publication by the academy of psychosomatic medicine research and evidence-based practice committee.

BACKGROUND Collaborative care interventions for psychiatric disorders combine several components integrated into the medical setting: (1) systematic psychiatric assessment, (2) use of a nonphysician care manager to perform longitudinal symptom monitoring, treatment interventions, and care coordination, and (3) specialist-provided stepped-care recommendations. Collaborative care interventions have now been evaluated in a wide spectrum of care settings and offer great promise as a way of increasing quality of patient care, improving health of populations, and reducing health care costs. METHODS A systematic search of PubMed/MEDLINE databases was performed for publications between January 1970 and May 2013 to identify articles describing collaborative care and related interventions. Identified articles were then evaluated independently by multiple reviewers for quality and importance; additional articles were identified by searching reference lists and through recommendations of senior content-matter experts. The articles considered to be both of high quality and most important were then placed into categories and annotated reviews performed. RESULTS Over 600 articles were identified of which 67 were selected for annotated review. The results reported in these articles indicate that collaborative care interventions for psychiatric disorders have been consistently successful in improving key outcomes in both research and clinical intervention studies; cost analyses also suggest that this model is cost effective. CONCLUSIONS Collaborative care models for psychiatric disorders are likely to serve an increasingly large role in health care given their effect on patient and population outcomes and their focus on integration of care.