Treatment of depression after coronary artery bypass surgery: a randomized controlled trial. Sertraline treatment of major depression in patients with acute MI or unstable angina. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. Infection, depression, and immunity in women after coronary artery bypass: a pilot study of cognitive behavioral therapy. Alprazolam treatment of postcoronary bypass anxiety and depression. Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. Improving psychologic adjustment to chronic illness in cardiac patients. The role of depression and anxiety. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction. Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial.
There has been little research on the treatment of depression after coronary artery bypass surgery.
                To test the efficacy of 2 nonpharmacological interventions for depression after coronary artery bypass surgery compared with usual care.
                A 12-week, randomized, single-blind clinical trial with outcome evaluations at 3, 6, and 9 months.
                Outpatient research clinic at Washington University School of Medicine, St Louis, Missouri.
                One hundred twenty-three patients who met the DSM-IV criteria for major or minor depression within 1 year after surgery.
                Twelve weeks of cognitive behavior therapy or supportive stress management. Approximately half of the participants were taking nonstudy antidepressant medications.
                Remission of depression, defined as a score of less than 7 on the 17-item Hamilton Rating Scale for Depression.
                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.
                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.
                clinicaltrials.gov Identifier: NCT00042198. Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease.
                To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions.
                Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001.
                A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%).
                After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n = 186) or placebo (n = 183) for 24 weeks.
                The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD.
                Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (P> or = .05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P =.049), but not the HAM-D (P =.14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P =.01), in the group with at least 1 prior episode of depression (72% vs 51%; P =.003), and in the more severe MDD group (78% vs 45%; P =.001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline.
                Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions. Few randomized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease (CAD). None have simultaneously evaluated an antidepressant and short-term psychotherapy.
                To document the short-term efficacy of a selective serotonin reuptake inhibitor (citalopram) and interpersonal psychotherapy (IPT) in reducing depressive symptoms in patients with CAD and major depression.
                The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy, a randomized, controlled, 12-week, parallel-group, 2 x 2 factorial trial conducted May 1, 2002, to March 20, 2006, among 284 patients with CAD from 9 Canadian academic centers. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosis of major depression of 4 weeks' duration or longer and had baseline 24-item Hamilton Depression Rating Scale (HAM-D) scores of 20 or higher.
                Participants underwent 2 separate randomizations: (1) to receive 12 weekly sessions of IPT plus clinical management (n = 142) or clinical management only (n = 142) and (2) to receive 12 weeks of citalopram, 20 to 40 mg/d (n = 142), or matching placebo (n = 142).
                The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D, administered blindly during centralized telephone interviews (tested at alpha = .033); the secondary outcome measure was self-reported Beck Depression Inventory II (BDI-II) score (tested at alpha = .017).
                Citalopram was superior to placebo in reducing 12-week HAM-D scores (mean difference, 3.3 points; 96.7% confidence interval [CI], 0.80-5.85; P = .005), with a small to medium effect size of 0.33. Mean HAM-D response (52.8% vs 40.1%; P = .03) and remission rates (35.9% vs 22.5%; P = .01) and the reduction in BDI-II scores (difference, 3.6 points; 98.3% CI, 0.58-6.64; P = .005; effect size = 0.33) also favored citalopram. There was no evidence of a benefit of IPT over clinical management, with the mean HAM-D difference favoring clinical management (-2.26 points; 96.7% CI, -4.78 to 0.27; P = .06; effect size, 0.23). The difference on the BDI-II did not favor clinical management (1.13 points; 98.3% CI, -1.90 to 4.16; P = .37; effect size = 0.11).
                This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management. Based on these results and those of previous trials, citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression.
                isrctn.org Identifier: ISRCTN15858091. Depression is common after coronary artery bypass graft (CABG) surgery, but little is known about its effect on post-CABG inflammation or infection or about the most effective treatment for post-CABG depression.
                (1) To determine ifpost-CABG depression is associated with increased infectious illness and (2) to test effects of cognitive behavioral therapy (CBT) on depressive symptoms, inflammatory biomarkers, and post-CABG infections in depressed post-CABG women.
                Randomized, controlled trial.
                Two urban tertiary care centers.
                Fifteen clinically depressed women in the first month after CABG, along with a comparison group of 37 non-depressed postCABG women, were studied. Inclusion criteria were: < or = 75 years old, English-speaking, undergoing first-time CABG, available for 6 months offollow-up, and without malignancy or autoimmune disorders.
                Eight weeks of individual home-based CBT.
                (1) Depressive symptoms measured by the Beck Depression Inventory, (2) natural killer cell cytotoxicity (NKCC) measured by 51Cr-release assay, (3) infectious illness episodes measured by the Modified Health Review, (4) interleukin (IL)-6 and C reactive protein (CRP) measured by enzyme immunoabsorbent assay.
                Clinically depressed post-CABG women exhibited decreased NKCC and a higher incidence of in-hospital fevers and infectious illness in the first 6 months after CABG. Among depressed women, CBT yielded moderate to large effects for improved NKCC (D=0.67) and decreased IL-6 (D=0.61), CRP (D=0.85), and postoperative infectious illnesses (D=0.93). CBT holds promise for improving depression and immunity and reducing infection and inflammation after CABG. The effectiveness of alprazolam in treating symptoms of anxiety and depression in 60 patients undergoing coronary bypass surgery was assessed in a double-blind, placebo-controlled study. The results indicate that alprazolam treatment for anxiety following coronary bypass surgery, particularly symptoms occurring in the immediate postoperative period, can significantly affect patient outcome. Specifically, only modest but statistically significant improvement was observed in the alprazolam-treated groups at 1-month follow-up; however, alprazolam-treated patients were significantly more likely to experience a very rapid anxiolytic effect by postoperative day 8. The implications of this study are discussed with respect to patient management and models for future studies of anxiety in postoperative patient populations. To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective serotonin reuptake inhibitors (SSRIs). Antidepressant effects have been limited.
                In a prospective multicenter study, 2177 patients with MI were evaluated for depressive disorder during the first year post MI. Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for major or minor depressive disorder were randomized to a 24-week, double-blind, placebo-controlled trial. Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach, with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale (Ham-D), and secondary outcomes the Beck Depression Inventory (BDI) and depression subscale of the Symptom Check List 90 items (dSCL-90) as well as the Clinical Global Impression (CGI) scale.
                Using the "last observation carried forward" (LOCF) method, mirtazapine did not show to be superior to placebo on the Ham-D, but did on the BDI, dSCL-90, and CGI scale over the acute treatment phase of 8 weeks (n = 91). Using mixed models analysis over the entire 24 weeks of treatment (n = 40), we did find a significant difference favoring mirtazapine to placebo on the Ham-D, BDI, and CGI, but on the dSCL-90, this difference was not significant.
                This trial shows efficacy of mirtazapine on primary and secondary depression measures. Mirtazapine seems to be safe in the treatment of post-MI depression. Depression and ischemic heart disease often are comorbid conditions and, in patients who have had a myocardial infarction, the presence of depression is associated with increased mortality. Patients with heart disease need a safe and effective treatment for depression.
                To compare the efficacy, cardiovascular effects, and safety of a specific serotonin reuptake inhibitor, paroxetine, with a tricyclic antidepressant, nortriptyline hydrochloride, in depressed patients with ischemic heart disease.
                Two-week placebo lead-in followed by a double-blind randomized 6-week medication trial.
                Research clinics in 4 university centers.
                Eighty-one outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder and with documented ischemic heart disease.
                Treatment with either paroxetine, 20 to 30 mg/d, or nortriptyline targeted to a therapeutic plasma level, 190 to 570 nmol/L (50-150 ng/mL), for 6 weeks.
                For effectiveness of treatment, a decline in the score of the Hamilton Rating Scale for Depression by 50% and final score of 8 or less; for cardiovascular safety, heart rate and rhythm, supine and standing systolic and diastolic blood pressures, electrocardiogram conduction intervals, indexes of heart rate variability, and rate of adverse events.
                By intent-to-treat analysis, 25 (61%) of 41 patients improved during treatment with paroxetine and 22 (55%) of 40 improved with nortriptyline. Neither drug significantly affected blood pressure or conduction intervals. Paroxetine had no sustained effects on heart rate or rhythm or indexes of heart rate variability, whereas patients treated with nortriptyline had a sustained 11% increase in heart rate from a mean of 75 to 83 beats per minute (P<.001) and a reduction in heart rate variability, as measured by the SD of all normal R-R intervals over a 24-hour period, from 112 to 96 (P<.01). Adverse cardiac events occurred in 1 (2%) of 41 patients treated with paroxetine and 7 (18%) of 40 patients treated with nortriptyline (P<.03).
                Paroxetine and nortriptyline are effective treatments for depressed patients with ischemic heart disease. Nortriptyline treatment was associated with a significantly higher rate of serious adverse cardiac events compared with paroxetine. Poor mood adjustment to chronic medical illness is often accompanied by decrements in function.
                To evaluate the effectiveness of a telephone-based intervention for psychologic distress and functional impairment in cardiac illness.
                Randomized, controlled trial.
                We recruited survivors of acute coronary syndromes using the Hospital and Anxiety Depression Scale (HADS) with scores indicative of mood disturbances at 1-month postdischarge. Recruited patients were randomized to experimental or control status. Intervention patients received 6 30-minute telephone counseling sessions to identify and address illness-related fears and concerns. Control patients received usual care. Patients' responses to the HADS and the Workplace Social Adjustment Scale (WSAS) were collected at baseline, 2, 3, and 6 months using interactive voice recognition technology. At baseline, the PRIME-MD was used to establish diagnosis of depression. We used mixed effects regression to study changes in outcomes.
                We enrolled 100 patients. Mean age was 60; 67% of the patients were male. Findings confirmed that the intervention group had a 27% improvement in depression symptoms (P=.05), 27% in anxiety (P=.02), and a 38% improvement in home limitations (P=.04) compared with controls. Symptom improvement tracked those for WSAS measures of home function (P=.04) but not workplace function.
                The intervention had a moderate effect on patient's emotional and functional outcomes that were observed during a critical period in patients' lives. Patient convenience, ease of delivery, and the effectiveness of the intervention suggest that the counseling can help patients adjust to chronic illness. Depression and low perceived social support (LPSS) after myocardial infarction (MI) are associated with higher morbidity and mortality, but little is known about whether this excess risk can be reduced through treatment.
                To determine whether mortality and recurrent infarction are reduced by treatment of depression and LPSS with cognitive behavior therapy (CBT), supplemented with a selective serotonin reuptake inhibitor (SSRI) antidepressant when indicated, in patients enrolled within 28 days after MI.Design, Setting, and
                Randomized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients (1084 women, 1397 men) enrolled from 8 clinical centers. Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression (HRSD); LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Social Support Instrument (ESSI). Random allocation was to usual medical care or CBT-based psychosocial intervention.
                Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months, plus group therapy when feasible, with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50% reduction in Beck Depression Inventory scores after 5 weeks.
                Composite primary end point of death or recurrent MI; secondary outcomes included change in HRSD (for depression) or ESSI scores (for LPSS) at 6 months.
                Improvement in psychosocial outcomes at 6 months favored treatment: mean (SD) change in HRSD score, -10.1 (7.8) in the depression and psychosocial intervention group vs -8.4 (7.7) in the depression and usual care group (P<.001); mean (SD) change in ESSI score, 5.1 (5.9) in the LPSS and psychosocial intervention group vs 3.4 (6.0) in the LPSS and usual care group (P<.001). After an average follow-up of 29 months, there was no significant difference in event-free survival between usual care (75.9%) and psychosocial intervention (75.8%). There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups (depression, LPSS, and depression and LPSS patients).
                The intervention did not increase event-free survival. The intervention improved depression and social isolation, although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients. Brain serotonin is known to possess sympathoinhibitory properties. The aim of this clinical physiologic study was to determine whether sertraline, a selective serotonin reuptake inhibitor, facilitates the rate of recovery of cardiac autonomic function after an acute myocardial infarction (MI) in patients with depression.
                Thirty-eight post-MI depressed patients were randomized to receive either sertraline 50 mg per day or placebo for 6 months. Depression was defined as a score >15 on the standardized Inventory to Diagnose Depression questionnaire taken at prehospital discharge and again within 2 weeks of the acute infarct. Eleven stable post-MI nondepressed patients served as a nonrandomized reference group during follow-up. Twenty-seven patients completed the randomization. All 3 groups were followed up closely in a multidisciplinary post-MI clinic where they underwent serial testing for both time and frequency domain heart rate variability (HRV) indices at baseline (1-2 weeks after MI) and at 6, 10, 14, 18, and 22 weeks. The rate of recovery of HRV was determined by use of a growth curve model based on repeated-measures analysis of variance. There was a linear rate of increase in the SD of 24-hour N-N intervals (SDNN) in the sertraline-treated group that paralleled that of the nondepressed reference group. This contrasted with a modest but significant decline in SDNN in the placebo group from 2 to 22 weeks (t = 2.10, P <.05). However, the short-term power spectral indices, while trending toward a more rapid rate of recovery in the treated group, did not reach statistical significance compared with the placebo group.
                In depressed patients who have survived the acute phase of an MI sertraline facilitates the rate of recovery of SDNN, a recognized predictor of clinical outcome. Depression and hostility are significant risk factors for mortality and morbidity after myocardial infarction (MI). Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease. This double-blind, placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI.
                Fifty-four patients with major depression after MI were randomly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind, placebo-controlled trial. Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks. To evaluate the efficacy of fluoxetine, the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Hostility Scale of the 90-item Symptom Check List (SCL-90) were used as primary measures of outcome. To evaluate the safety of fluoxetine, cardiac function was measured before and after treatment with echocardiography and electrocardiography.
                The a priori difference in antidepressive efficacy (4-point difference in HAMD-17 scores between the fluoxetine and placebo groups) was not met. However, the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 (48 vs. 26%, p = .05). Among patients with mild depression (HAMD-17 score < or =21), HAMD-17 scores were significantly different (p < .05) between the fluoxetine and placebo groups at weeks 9 (by 5.4 points) and 25 (by 5.8 points). Also, hostility scores at week 25 were significantly reduced among patients receiving fluoxetine (p = .02). Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine. Conclusions: Although the overall difference between the fluoxetine and placebo groups was not significant, there was a trend favoring fluoxetine in this relatively small sample. The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease. In addition, fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility. The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event.