Brian C. Steinmeyer

Treatment of Depression After Coronary Artery Bypass Surgery: A Randomized Controlled Trial

CONTEXT There has been little research on the treatment of depression after coronary artery bypass surgery. OBJECTIVE To test the efficacy of 2 nonpharmacological interventions for depression after coronary artery bypass surgery compared with usual care. DESIGN A 12-week, randomized, single-blind clinical trial with outcome evaluations at 3, 6, and 9 months. SETTING Outpatient research clinic at Washington University School of Medicine, St Louis, Missouri. PATIENTS One hundred twenty-three patients who met the DSM-IV criteria for major or minor depression within 1 year after surgery. INTERVENTION Twelve weeks of cognitive behavior therapy or supportive stress management. Approximately half of the participants were taking nonstudy antidepressant medications. MAIN OUTCOME MEASURE Remission of depression, defined as a score of less than 7 on the 17-item Hamilton Rating Scale for Depression. RESULTS Remission of depression occurred by 3 months in a higher proportion of patients in the cognitive behavior therapy (71%) and supportive stress-management (57%) arms than in the usual care group (33%) (chi(2)(2) = 12.22, P = .002). Covariate-adjusted Hamilton scores were lower in the cognitive behavior therapy (mean [standard error], 5.5 [1.0]) and the supportive stress-management (7.8 [1.0]) arms than in the usual care arm (10.7 [1.0]) at 3 months. The differences narrowed at 6 months, but the remission rates differed again at 9 months (73%, 57%, and 35%, respectively; chi(2)(2) = 12.02, P = .003). Cognitive behavior therapy was superior to usual care at most points on secondary measures of depression, anxiety, hopelessness, stress, and quality of life. Supportive stress management was superior to usual care only on some of the measures. CONCLUSIONS Both cognitive behavior therapy and supportive stress management are efficacious for treating depression after coronary artery bypass surgery, relative to usual care. Cognitive behavior therapy had greater and more durable effects than supportive stress management on depression and several secondary psychological outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00042198.

Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial.

CONTEXT Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids. OBJECTIVE To determine whether omega-3 improves the response to sertraline in patients with major depression and coronary heart disease (CHD). DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial. Between May 2005 and December 2008, 122 patients in St Louis, Missouri, with major depression and CHD were randomized. INTERVENTIONS After a 2-week run-in period, all patients were given 50 mg/d of sertraline and randomized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters (930 mg of eicosapentaenoic acid [EPA] and 750 mg of docosahexaenoic acid [DHA]) (n=62) or to corn oil placebo capsules (n=60) for 10 weeks. MAIN OUTCOME MEASURES Scores on the Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression (HAM-D). RESULTS Adherence to the medication regimen was 97% or more in both groups for both medications. There were no differences in weekly BDI-II scores (treatment x time interaction = 0.02; 95% confidence interval [CI], -0.33 to 0.36; t(112) = 0.11; P = .91), pre-post BDI-II scores (placebo, 14.8 vs omega-3, 16.1; 95% difference-in-means CI, -4.5 to 2.0; t(116) = -0.77; P = .44), or HAM-D scores (placebo, 9.4 vs omega-3, 9.3; 95% difference-in-means CI, -2.2 to 2.4; t(115) = 0.12; P = .90). The groups did not differ on predefined indicators of depression remission (BDI-II < or = 8: placebo, 27.4% vs omega-3, 28.3%; odds ratio [OR], 0.96; 95% CI, 0.43-2.15; t(113) = -0.11; P = .91) or response (> 50% reduction in BDI-II from baseline: placebo, 49.0% vs omega-3, 47.7%; OR, 1.06; 95% CI, 0.51-2.19; t(112) = 0.15; P = .88). CONCLUSIONS Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks, compared with sertraline and placebo. Whether higher doses of omega-3 or sertraline, a different ratio of EPA to DHA, longer treatment, or omega-3 monotherapy can improve depression in patients with CHD remains to be determined. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00116857.

Depression and five year survival following acute myocardial infarction: A prospective study

Depression has been shown to be a risk factor for mortality during the 12 months following an acute myocardial infarction (MI), but few studies have examined whether it is associated with increased risk over longer periods. Most of the existing studies utilized depression questionnaires rather than diagnostic interviews, the gold standard for clinical depression diagnosis. The purpose of this study was to determine whether interview-diagnosed clinical depression affects survival for at least 5 years after an acute MI. Vital status was determined for 163 patients with major depression, 195 with minor depression or dysthymia, and 408 nondepressed patients, during a median follow-up period of 60 months after an acute MI. Survival analysis was used to model time from the index MI to death. There were 106 deaths during the follow-up. After adjusting for other risk factors for mortality, patients with either major or minor depression (HR=1.76; 95% CI: 1.19 to 2.60), major depression alone (HR=1.87; 95% CI: 1.17 to 2.98), or minor depression alone (HR=1.67; 95% CI: 1.06 to 2.64) were at higher risk for all-cause mortality compared to the nondepressed patients. Depression is an independent risk factor for death 5 years after an acute MI. Even minor depression is associated with an increased risk. Although it is not known whether treating depression can improve survival, patients with depression should be recognized as being at increased risk long after their acute MI.

Cognitive Behavior Therapy for Depression and Self-Care in Heart Failure Patients: A Randomized Clinical Trial

IMPORTANCE Depression and inadequate self-care are common and interrelated problems that increase the risks of hospitalization and mortality in patients with heart failure (HF). OBJECTIVE To determine the efficacy of an integrative cognitive behavior therapy (CBT) intervention for depression and HF self-care. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial with single-blind outcome assessments. Eligible patients were enrolled at Washington University Medical Center in St Louis between January 4, 2010, and June 28, 2013. The primary data analyses were conducted in February 2015. The participants were 158 outpatients in New York Heart Association Class I, II, and III heart failure with comorbid major depression. INTERVENTIONS Cognitive behavior therapy delivered by experienced therapists plus usual care (UC), or UC alone. Usual care was enhanced in both groups with a structured HF education program delivered by a cardiac nurse. MAIN OUTCOMES AND MEASURES The primary outcome was severity of depression at 6 months as measured by the Beck Depression Inventory. The Self-Care of Heart Failure Index Confidence and Maintenance subscales were coprimary outcomes. Secondary outcomes included measures of anxiety, depression, physical functioning, fatigue, social roles and activities, and quality of life. Hospitalizations and deaths were exploratory outcomes. RESULTS One hundred fifty-eight patients were randomized to UC (n = 79) or CBT (n = 79). Within each arm, 26 (33%) of the patients were taking an antidepressant at baseline. One hundred thirty-two (84%) of the participants completed the 6-month posttreatment assessments; 60 (76%) of the UC and 58 (73%) of the CBT participants completed every follow-up assessment (P = .88). Six-month depression scores were lower in the CBT than the UC arm on the Beck Depression Inventory (BDI-II) (12.8 [10.6] vs 17.3 [10.7]; P = .008). Remission rates differed on the BDI-II (46% vs 19%; number needed to treat [NNT] = 3.76; 95% CI, 3.62-3.90; P < .001) and the Hamilton Depression Scale (51% vs 20%; NNT = 3.29; 95% CI, 3.15-3.43; P < .001). The groups did not differ on the Self-Care Maintenance or Confidence subscales. The mean (SD) Beck Depression Inventory scores 6 months after randomization were lower in the CBT (12.8 [10.6]) than the UC arm (17.3 [10.7]), P = .008. There were no statistically significant differences between the groups on the Self-Care Maintenance or Confidence subscale scores or on physical functioning measures. Anxiety and fatigue scores were lower and mental- and HF-related quality of life and social functioning scores were higher at 6 months in the CBT than the UC arm, and there were fewer hospitalizations in the intervention than the UC arm. CONCLUSIONS AND RELEVANCE A CBT intervention that targets both depression and heart failure self-care is effective for depression but not for HF self-care or physical functioning relative to enhanced UC. Additional benefits include reduced anxiety and fatigue, improved social functioning, and better health-related quality of life. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01028625.

History of depression and survival after acute myocardial infarction.

Objective: To compare survival in post-myocardial (MI) participants from the Enhancing Recovery In Coronary Heart Disease (ENRICHD) clinical trial with a first episode of major depression (MD) and those with recurrent MD, which is a risk factor for mortality after acute MI. Recent reports suggest that the level of risk may depend on whether the comorbid MD is a first or a recurrent episode. Methods: Survival was compared over a median of 29 months in 370 patients with an initial episode of MD, 550 with recurrent MD, and 408 who were free of depression. Results: After adjusting for an all-cause mortality risk score, initial Beck Depression Inventory score, and the use of selective serotonin reuptake inhibitor antidepressants, patients with a first episode of MD had poorer survival (18.4% all-cause mortality) than those with recurrent MD (11.8%) (hazard ratio (HR) = 1.4; 95% Confidence Interval (CI) = 1.0–2.0; p = .05). Both first depression (HR = 3.1; 95% CI = 1.6–6.1; p = .001) and recurrent MD (HR = 2.2; 95% CI = 1.1–4.4; p = .03) had significantly poorer survival than did the nondepressed patients (3.4%). A secondary analysis of deaths classified as probably due to a cardiovascular cause resulted in similar HRs, but the difference between depression groups was not significant. Conclusions: Both initial and recurrent episodes of MD predict shorter survival after acute MI, but initial MD episodes are more strongly predictive than recurrent episodes. Exploratory analyses suggest that this cannot be explained by more severe heart disease at index, poorer response to depression treatment, or a higher risk of cerebrovascular disease in patients with initial MD episodes. MI = myocardial infarction; MD = major depression; ENRICHD = Enhancing Recovery In Coronary Heart Disease; DISH = Depression Interview and Structured Hamilton; BDI = Beck Depression Inventory; HR = hazard ratio; SSRI = selective serotonin reuptake inhibitor; HAM-D = Hamilton Rating Scale for Depression; UC = usual care; LVEF = left ventricular ejection fraction; ACS = acute coronary syndrome; HADS = Hospital Anxiety and Depression Scale.

Heart rate turbulence, depression, and survival after acute myocardial infarction.

Objective: Depression is a risk factor for mortality after acute myocardial infarction (AMI), possibly as a result of altered autonomic nervous system (ANS) modulation of heart rate (HR) and rhythm. The purposes of this study were to determine: a) whether depressed patients are more likely to have an abnormal HR response (i.e., abnormal turbulence) to premature ventricular contractions (VPCs), and b) whether abnormal HR turbulence accounts for the effect of depression on increased mortality after AMI. Methods: Ambulatory electrocardiographic data were obtained from 666 (316 depressed, 350 nondepressed) patients with a recent AMI; 498 had VPCs with measurable HR turbulence. Of these, 260 had normal, 152 had equivocal, and 86 had abnormal HR turbulence. Patients were followed for up to 30 (median = 24) months. Results: Depressed patients were more likely to have abnormal HR turbulence (risk factor adjusted odds ratio = 1.8; 95% confidence interval [CI] = 1.0–3.0; p = .03) and have worse survival (odds ratio = 2.4; 95% CI = 1.2–4.6; p = .02) than nondepressed patients. When HR turbulence was added to the model, the adjusted hazard ratio for depression decreased to 1.9 (95% CI = 0.9–3.8; p = .08), and to 1.6 (95% CI = 0.8–3.4; p = .18) when a measure of HR variability (LnVLF) was added. The hazard was found to differ over time with depression posing little risk for mortality in year 1 but greater risk in years 2 and 3 of the follow up. Conclusion: ANS dysregulation may partially mediate the increased risk for mortality in depressed patients with frequent VPCs after an AMI. ANS = autonomic nervous system; HR = heart rate; VPC = premature ventricular contraction; AECG = ambulatory electrocardiography; AMI = acute myocardial infarction; LnVLF = natural log of very low frequency; LVEF = left ventricular ejection fraction; TO = turbulence onset; TS = turbulence slope.

Depression and Rehospitalization Following Acute Myocardial Infarction

Background—Elevated scores on depression symptom questionnaires predict rehospitalization after acute myocardial infarction (AMI). Whether the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, depressive disorders predict rehospitalization after AMI is unknown. Methods and Results—Participants (n=766) in an Enhancing Recovery and Coronary Heart Disease ancillary study were classified by diagnostic interview as having no depression, minor depression, or major depression after AMI. Cardiac rehospitalizations were tracked for up to 42 months. Cox proportional hazards regression was used to model the effect of depressive disorder on time to first cardiac rehospitalization, controlling for mortality risk factors. Logistic regression was used to compare the accuracy with which rehospitalization could be predicted by depression diagnosis or by the Beck Depression Inventory (BDI). Secondary analyses examined the effects of depression on the cumulative number of all-cause rehospitalizations, length of stay, and emergency department visits. Compared with patients without depression, patients with either minor or major depression were hospitalized sooner (minor depression adjusted hazard ratio, 2.22; 95% CI, 1.59–3.08; P<0.001; major depression adjusted hazard ratio, 2.54; 95% CI, 1.84–3.53; P<0.001), had more hospitalizations (minor, P<0.001; major, P<0.001) and emergency department visits (minor, P=0.003; major, P<0.001), and spent more days in the hospital (minor, P<0.001; major, P<0.001). The interview and questionnaire methods of assessing depression did not significantly differ in their overall accuracy of predicting rehospitalization. Conclusions—Depressive disorders increase the risk of rehospitalization after AMI. Future work should focus on developing multivariable models to predict risk of rehospitalization after AMI, and depression should be included in these.

Effect of omega-3 fatty acids on heart rate variability in depressed patients with coronary heart disease.

Objective: To determine whether omega-3 fatty acid (FA) increases the natural log of very low frequency (lnVLF) power, an index of heart rate variability (HRV), and reduces 24-hour heart rate (HR) in depressed patients with coronary heart disease (CHD). Low intake of omega-3 FAs is associated with depression and with low HRV, and all three are associated with an increased risk of death in patients with CHD. Methods: Thirty-six depressed patients with CHD randomized to receive 50 mg of sertraline and 2 g of omega-3/day, and 36 randomized to sertraline and a placebo, had 24-hour HRV measured at baseline and after 10 weeks of treatment. Results: There was a significant treatment × time interaction for covariate adjusted lnVLF (p = .009), for mean 24-hour HR (p = .03), and for 1-minute resting HR (p = .02). The interaction was not significant for three other measures of HRV. LnVLF did not change over time in the omega-3 arm but decreased in the placebo arm (p = .002), suggesting that omega-3 may have prevented or slowed deterioration in cardiac autonomic function. Conclusions: The effects of omega-3 FAs on lnVLF and HR, although modest, were detected after only 10 weeks of treatment with 2 g per day of omega-3. Whether a longer course of treatment or a higher dose of omega-3 would further decrease HR, improve other indices of HRV, or reduce mortality in depressed CHD patients should be investigated. CHD = coronary heart disease; FAs = fatty acids; EPA = eicosapentaenoic acid; DHA = docosahexaenoic acid; HRV = heart rate variability; VLF = very low frequency; BDI-II = Beck Depression Inventory; RBC = red blood cell; HR = heart rate; ULF = ultra low frequency; ECG = electrocardiogram; bpm = beats per minute; MI = myocardial infarction.

The Efficacy of Auriculotherapy for Smoking Cessation: A Randomized, Placebo-Controlled Trial

Background: Quitting smoking remains a challenge for almost one-third of the military veteran population. Alternatives to pharmacological therapies such as acupuncture, acupressure, and electrical stimulation have received minimal attention in research but have been widely reported to be popular and safe interventions for smoking cessation. Methods: This randomized, double-blind, placebo-controlled clinical trial of 125 veterans was conducted to determine whether aural electrical stimulation (auriculotherapy) once a week for 5 consecutive weeks is associated with a higher rate of smoking abstinence are than observed with sham stimulation. Results: Auriculotherapy was found to be safe and largely free from significant side effects. However, there was no difference in the rate of smoking cessation between those participants who received true auriculotherapy and those who received sham auriculotherapy. The auriculotherapy group achieved a rate of 20.9% abstinence versus 17.9% for the placebo arm after 6 weeks. Conclusion: The results of this randomized, controlled clinical trial do not support the use of auriculotherapy to assist with smoking cessation. It is possible that a longer treatment duration, more frequent sessions, or other modifications of the intervention protocol used in this study may result in a different outcome. However, based on the results of this study, there is no evidence that auriculotherapy is superior to placebo when offered once a week for 5 weeks, as described in previous uncontrolled studies.

Depression and Multiple Rehospitalizations in Patients With Heart Failure.

There have been few studies of the effect of depression on rehospitalization in patients with heart failure (HF), and even fewer on its role in multiple rehospitalizations.