Sequential Interventions for Major Depression and Heart Failure Self-Care: A Randomized Clinical Trial.

BACKGROUND: Major depression and inadequate self-care are common in patients with heart failure (HF). Little is known about how to intervene when both problems are present. This study examined the efficacy of a sequential approach to treating these problems. METHODS: Stepped Care for Depression in HF was a single-site, single-blind, randomized controlled trial of cognitive behavior therapy (CBT) versus usual care (UC) for major depression in patients with HF. The intensive phase of the CBT intervention lasted between 8 and 16 weeks, depending upon the rate of improvement in depression. All participants received a tailored HF self-care intervention that began 8 weeks after randomization. The intensive phase of the self-care intervention ended at 16 weeks post-randomization. The coprimary outcome measures were the Beck Depression Inventory (version 2) and the Maintenance scale of the Self-Care of HF Index (v6.2) at week 16. RESULTS: One hundred thirty-nine patients with HF and major depression were enrolled; 70 were randomized to UC and 69 to CBT. At week 16, the patients in the CBT arm scored 4.0 points ([95% CI, -7.3 to -0.8]; P=0.02) lower on the Beck Depression Inventory, version 2 than those in the usual care arm. Mean scores on the Self-Care of HF Index Maintenance scale were not significantly different between the groups ([95% CI, -6.5 to 1.5]; P=0.22). CONCLUSIONS: CBT is more effective than usual care for major depression in patients with HF. However, initiating CBT before starting a tailored HF self-care intervention does not increase the benefit of the self-care intervention. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02997865.

A Randomized Placebo-Controlled Trial of Omega-3 and Sertraline in Depressed Patients With or at Risk for Coronary Heart Disease.

OBJECTIVE: Studies of depressed psychiatric patients have suggested that antidepressant efficacy can be increased by adding eicosapentaenoic acid (EPA), one of the omega-3 fatty acids found in fish oils. The purpose of this study was to determine whether the addition of EPA improves the response to sertraline in depressed patients with or at high risk for coronary heart disease (CHD). METHODS: Between May 2014 and June 2018, 144 patients with DSM-5 major depressive disorder seen at the Washington University School of Medicine with or at high risk for CHD were randomized to receive either 50 mg/d of sertraline and 2 g/d of EPA or 50 mg/d of sertraline and corn oil placebo capsules for 10 weeks. The Beck Depression Inventory II (BDI-II) was the primary outcome measure. RESULTS: After 10 weeks of treatment, there were no differences between the arms on the mean baseline-adjusted BDI-II (placebo, 10.3; EPA, 12.1; P = .22), the 17-item Hamilton Depression Rating Scale (placebo, 7.2; EPA, 8.0; P = .40), or the 10-week remission rate (BDI-II score ≤ 8: placebo, 50.6%; EPA, 46.7%; odds ratio = 0.85; 95% CI, 0.43 to 1.68; P = .63). CONCLUSIONS: Augmentation of sertraline with 2 g/d of EPA for 10 weeks did not result in greater improvement in depressive symptoms compared to sertraline and corn oil placebo in patients with major depressive disorder and CHD or CHD risk factors. Identifying the characteristics of cardiac patients whose depression may benefit from omega-3 and clarifying the pathways linking omega-3 to improvement in depression symptoms are important directions for future research. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02021669; FDA IND registration number: 121107.

Use of the PROMIS® Depression scale and the Beck Depression Inventory in patients with heart failure.

OBJECTIVE: This study evaluated agreement between the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Depression scale and the Beck Depression Inventory (BDI-II) in patients with heart failure and comorbid major depression. METHOD: The BDI-II and the computerized adaptive test version of the PROMIS® Depression scale were administered at baseline to 158 participants in a randomized controlled trial of cognitive behavior therapy for major depression in patients with heart failure. A crosswalk table (Choi, Schalet, Cook, & Cella, 2014) was used to transform the PROMIS® scores into "linked" BDI-II equivalent scores. Bland-Altman plots, histograms, and scatterplots were used to visualize the agreement between these scores at baseline and 6 months, and intraclass correlation coefficients (ICCs) were calculated for each occasion to quantify the agreement. Treatment effects and change scores were also examined. RESULTS: The measures agreed moderately at baseline (ICC = 0.52, p < .0001) and strongly at 6 months (ICC = 0.77, p < .0001), but on average, the linked and observed BDI-II scores differed by 3.1 points at baseline (p < .0001) and -0.17 points at 6 months (p = .78). The discrepancies were considerably larger in many individual cases on both occasions. CONCLUSIONS: The PROMIS® Depression scale is likely to play an important role in research on depression in patients with heart failure, but for now, it should be used in addition to rather than instead of the BDI-II in studies in which the BDI-II would ordinarily be used. Additional research is needed to evaluate the validity and utility of the PROMIS® Depression scale in patients with heart failure. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Residual Symptoms After Treatment for Depression in Patients With Coronary Heart Disease.

OBJECTIVE: Depression is associated with an increased risk of mortality in patients with coronary heart disease (CHD). The risk may be reduced in patients who remit with adequate treatment, but few patients achieve complete remission. The purpose of this study was to identify the symptoms that persist despite aggressive treatment for depression in patients with CHD. METHODS: One hundred twenty-five patients with stable CHD who met the DSM-IV criteria for a moderate-to-severe major depressive episode completed treatment with cognitive behavior therapy, either alone or combined with an antidepressant, for up to 16 weeks. Depression symptoms were assessed at baseline and after 16 weeks of treatment. RESULTS: The M (SD) Beck Depression Inventory scores were 30.0 (8.6) at baseline and 8.3 (7.5) at 16 weeks. Seventy seven (61%) of the participants who completed treatment met remission criteria (Hamilton Rating Scale for Depression ≤7) at 16 weeks. Loss of energy and fatigue were the most common posttreatment symptoms both in remitters (n = 44, 57%; n = 34, 44.2%) and nonremitters (n = 42, 87.5%; n = 35, 72.9%). These symptoms were not predicted by baseline depression severity, anxiety, demographic, or medical variables including inflammatory markers or cardiac functioning or by medical events during depression treatment. CONCLUSIONS: Fatigue and loss of energy often persist in patients with CHD even after otherwise successful treatment for major depression. These residual symptoms may increase the risks of relapse and mortality. Development of effective interventions for these persistent symptoms is a priority for future research.

Clinical predictors of depression treatment outcomes in patients with coronary heart disease.

OBJECTIVES: Patients with coronary heart disease (CHD) who respond to treatment for depression are at lower risk of mortality than are nonresponders. This study sought to determine whether variables that have been shown to predict both depression treatment outcomes in psychiatric patients and cardiac events in patients with CHD, also predict poor response to depression treatment in patients with CHD. METHODS: One hundred fifty-seven patients with stable CHD who met the DSM-IV criteria for a major depressive episode were treated with cognitive behavior therapy (CBT) for 16weeks, either alone or in combination with an antidepressant. RESULTS: The mean Beck Depression Inventory (BDI-II) score was 30.2±8.5 at baseline and 8.5±7.8 at 16weeks. Over 50% of the participants were in remission (HAM-D-17 score ≤7) at the end of treatment. Of the hypothesized predictors, severe depression at baseline (p=0.02), stressful life events during the first (p=0.03) and last (p<0.0001) 8weeks of treatment, and the completion of CBT homework assignments (p=0.001) predicted depression outcomes. History of prior episodes, anxiety symptoms, antidepressant therapy at study enrollment, and medical hospitalizations or emergency department visits during treatment did not predict treatment outcome. CONCLUSIONS: Patients who are under considerable stress do not respond as well to evidence-based treatments for depression as do patients with less stress. If future studies support these findings, more work will be needed to better address stressful life events in patients who may otherwise remain at high risk for mortality and medical morbidity following depression treatment.

Collaborative care for depression symptoms in an outpatient cardiology setting: A randomized clinical trial.

BACKGROUND: Depression is a risk factor for morbidity and mortality in patients with coronary heart disease. Finding effective methods for identifying and treating depression in these patients is a high priority. The purpose of this study was to determine whether collaborative care (CC) for patients who screen positive for depression during an outpatient cardiology visit results in greater improvement in depression symptoms and better medical outcomes than seen in patients who screen positive for depression but receive only usual care (UC). METHODS: Two hundred-one patients seen in an outpatient cardiology clinic who screened positive for depression during an outpatient visit were randomized to receive either CC or UC. Recommendations for depression treatment and ongoing support and monitoring of depression symptoms were provided to CC patients and their primary care physicians (PCPs) for up to 6months. RESULTS: There were no differences between the arms in mean Beck Depression Inventory-II scores(CC, 15.9; UC, 17.4; p=.45) or in depression remission rates(CC, 32.5%; UC, 26.2%; p=0.34) after 6months, or in the number of hospitalizations after 12months (p=0.73). There were fewer deaths among the CC (1/100) than UC patients (8/101) (p=0.03). CONCLUSIONS: This trial did not show that CC produces better depression outcomes than UC. Screening led to a higher rate of depression treatment than was expected in the UC group, and delays in obtaining depression treatment from PCPs may have reduced treatment effectiveness for the CC patients. A different strategy for depression treatment following screening in outpatient cardiology services is needed.

Nighttime heart rate predicts response to depression treatment in patients with coronary heart disease.

BACKGROUND: Previous studies suggest that patients with coronary heart disease (CHD) who do not respond to treatment for depression are at higher risk of mortality than are treatment responders. The purpose of this study was to determine whether elevated nighttime heart rate (HR) and low heart rate variability (HRV), both of which have been associated with depression and with cardiac events in patients with CHD, predict poor response to depression treatment in patients with CHD. METHODS: Patients with stable CHD and a current major depressive episode completed 24h ambulatory ECG monitoring and were then treated for up to 16 weeks with cognitive behavior therapy (CBT), either alone or in combination with an antidepressant. Pre-treatment HR and HRV were calculated for 124 patients who had continuous ECG from early evening to mid-morning. RESULTS: Following treatment, 64 of the 124 patients (52%) met study criteria for remission (Hamilton Rating Scale for Depression score≤7). Prior to treatment, non-remitters had higher nighttime HR (p=0.03) and lower nighttime HRV (p=0.01) than did the remitters, even after adjusting for potential confounds. LIMITATIONS: Polysomnography would have provided information about objective sleep characteristics and sleep disorders. More CBT sessions and higher doses of antidepressants may have resulted in more participants in remission. CONCLUSIONS: High nighttime HR and low nighttime HRV predict a poor response to treatment of major depression in patients with stable CHD. These findings may help explain why patients with CHD who do not respond to treatment are at higher risk for mortality.

Baseline blood levels of omega-3 and depression remission: a secondary analysis of data from a placebo-controlled trial of omega-3 supplements.

OBJECTIVE: Depression is associated with low red blood cell (RBC) levels of 2 omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), suggesting that omega-3 supplements might improve depression. However, clinical trials have produced mixed results. The purpose of this secondary analysis of data from a randomized controlled trial was to determine whether baseline blood levels of omega-3, which are known to vary widely among individuals, predict depression outcomes. METHOD: The percentages of EPA, DHA, and the omega-6 arachidonic acid (AA) were measured in RBCs at baseline and posttreatment in 122 participants with DSM-IV major depression who were randomly assigned between May 2005 and December 2008 to receive either 50 mg/d of sertraline and a daily dosage of 930 mg EPA/750 mg DHA or sertraline plus placebo. Associations between baseline omega-3 RBC levels and remission of depression (17-item Hamilton Depression Rating Scale score ≤ 7) were analyzed by treatment arm. RESULTS: Among participants in the omega-3 arm, baseline RBC levels of EPA + DHA (P = .002) and the EPA + DHA:AA ratio (P = .003) were significantly higher among those whose depression subsequently remitted compared with those whose depression did not remit. No associations were detected in the sertraline plus placebo arm. Baseline levels of EPA (P = .03) and the EPA + DHA:AA ratio (P = .04) moderated the relationship between treatment arm and depression outcomes. CONCLUSIONS: High baseline RBC levels of EPA and DHA and a high EPA + DHA:AA ratio predict favorable depression outcomes in patients receiving omega-3 supplements. Omega-3 supplementation may be an effective treatment for depression, but the requisite dosage and duration of treatment may depend on the patient's baseline level of omega-3 fatty acids. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00116857.

Cardiac Risk Markers and Response to Depression Treatment in Patients With Coronary Heart Disease.

BACKGROUND: Depression is associated with an increased risk of mortality in patients with coronary heart disease. There is evidence that this risk may be reduced in patients who respond to depression treatment. The purpose of this study was to determine whether cardiac risk markers predict poor response to depression treatment and, second, whether they improve with successful treatment. METHODS: One hundred fifty-seven patients with stable coronary heart disease who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for a moderate to severe major depressive episode were treated with cognitive behavior therapy, either alone or combined with an antidepressant, for up to 16 weeks. Depression, physical activity, sleep quality, thyroid hormones (total thyroxine [T4] and free T4), and inflammatory blood markers (C-reactive protein, interleukin-6, tumor necrosis factor) were assessed at baseline and after 16 weeks of treatment. RESULTS: The mean (SD) Beck Depression Inventory scores were 30.2 (8.5) at baseline and 8.5 (7.8) at 16 weeks. More than 50% of the participants met the criteria for depression remission (17-item Hamilton Rating Scale for Depression ≤ 7) at 16 weeks. Only free T4 thyroid hormone at baseline predicted poor response to depression treatment after adjustment for potential confounders (p = .004). Improvement in sleep quality (p = .012) and physical activity level (p = .041) correlated with improvement in depression. None of the inflammatory markers predicted posttreatment depression or changed with depression. CONCLUSIONS: Thyroid hormone (T4) level predicted depression treatment outcome, and improvement in depression correlated with improvement in sleep and physical activity. More detailed studies of thyroid function and objective assessments of sleep and physical activity in relation to depression improvement and cardiac outcomes are needed.

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.

Perspective: Upcoming paradigm shifts for psychiatry in clinical care, research, and education.

Psychiatry is facing a crisis fueled by a fragmented and inefficient system of care delivery and a disconnection between the state of research and the state of psychiatry education and practice. Many factors contribute to the current state of psychiatric care. Psychiatry is a shortage specialty, and this will become worse in the near future. In addition, financial pressures have led to decreases in psychiatric inpatient and outpatient services and to shorter lengths of hospitalization for even the sickest patients. This has resulted in fragmented care and an overreliance on polypharmacy. To reach the large number of patients needing psychiatric services, health care systems must change and take advantage of collaborative and integrative care models and new technologies. Psychiatrists must learn to partner more effectively with primary care providers to extend their expertise to the greatest number of patients. Currently, psychiatric diagnosis is based on a criteria-based system that was developed in the 1970s. Advances in systems and molecular neuroscience are beginning to elucidate specific brain systems that are dysfunctional in psychiatric illness. This has the potential to revolutionize psychiatric diagnosis and treatment in the future. However, psychiatry has not yet been successful in incorporating the language of this research into clinically meaningful terminology. If neuroscientific progress is to be translated into clinical advances, this must change. Residency programs must better prepare their graduates to keep up with a psychiatry literature that will increasingly use the language of neural circuits to describe psychiatric symptomatology and treatments.

Obstructive sleep apnea/hypopnea syndrome and poor response to sertraline in patients with coronary heart disease.

OBJECTIVE: Evidence from several clinical trials in patients with coronary heart disease suggests that depression that does not respond to treatment is associated with a particularly high risk of adverse cardiac outcomes. The purpose of this study was to determine whether obstructive sleep apnea/hypopnea syndrome (OSAHS) is associated with a poor response to antidepressant medication in patients with coronary heart disease. METHOD: This was a secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of omega-3 fatty-acid augmentation of sertraline for depression in patients with coronary heart disease. Patients with documented coronary heart disease were recruited between May 2005 and December 2008 from cardiology practices in St Louis, Missouri, and through cardiac diagnostic laboratories affiliated with Washington University School of Medicine, St Louis, Missouri. One hundred five patients (mean age = 58 years) with coronary heart disease and current major depressive disorder (DSM-IV) were randomized to receive sertraline plus either omega-3 or placebo for 10 weeks. Cyclical heart-rate patterns associated with OSAHS were detected via ambulatory electrocardiography prior to treatment. Symptoms of depression were measured at baseline and follow-up with the Beck Depression Inventory-II (BDI-II) and the 17-item Hamilton Depression Rating Scale (HDRS-17). The primary endpoint was the BDI-II score at 10 weeks. RESULTS: Thirty of the 105 patients (29%) were classified as having probable moderate to severe OSAHS on the basis of nighttime heart-rate patterns. These OSAHS patients had significantly higher scores on both the BDI-II (t = -2.78, P = .01) and the HDRS-17 (t = -2.33, P = .02) at follow-up as compared to the reference group. Adjustment for baseline depression score, treatment arm (omega-3 vs placebo), body mass index, and inflammatory markers did not change the results. Patients with OSAHS reported higher item scores at follow-up on all depressive symptoms measured with the BDI-II compared to those without OSAHS. CONCLUSIONS: Obstructive sleep apnea/hypopnea syndrome is associated with a relatively poor response to sertraline treatment for depression. Future research should determine the contribution of OSAHS to the increased risk of adverse cardiac outcome associated with treatment-resistant depression.

Inflammation and treatment response to sertraline in patients with coronary heart disease and comorbid major depression.

OBJECTIVE: Treatment-resistant depression has recently emerged as a marker of increased risk for morbidity and mortality in patients with coronary heart disease (CHD). Studies in depressed patients without CHD suggest that elevated markers of inflammation predict poor response to treatment. This may help to explain the increased risk of cardiac events associated with depression. We therefore studied the relationship between pretreatment markers of inflammation and treatment response in patients with CHD and major depression. METHODS: This was a planned, secondary analysis of a clinical trial in which 122 patients with CHD and comorbid major depression were randomly assigned to 50 mg of sertraline plus 2 g/day omega-3 fatty acids or to 50 mg of sertraline plus 2 g/day corn oil placebo capsules for ten weeks. Depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II). Blood samples were collected at baseline to determine levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The primary outcome was the post-treatment BDI-II depression score. RESULTS: Baseline levels of hs-CRP, IL-6, and TNF-α were not associated with the 10-week post-treatment depression score (P=.89, P=.88, and P=.31, respectively). Treatment responders (>50% reduction from baseline BDI-II score) did not differ from non-responders in either baseline hs-CRP, IL-6, or TNF-α (P=.83, P=.93, and P=.24, respectively). Similarly, depression remitters (BDI-II ≤8 at post-treatment) did not differ from non-remitters on the three baseline inflammation markers. CONCLUSION: These findings do not support the hypothesis that elevated baseline inflammatory markers predict poor response to sertraline in patients with CHD and major depression. The explanation for the increased risk of cardiac events associated with poor response to depression treatment remains unclear.

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.

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.

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.

Efficacy of sertraline in prevention of depression recurrence in older versus younger adults with diabetes.

OBJECTIVE: Sertraline maintenance therapy effectively delays recurrence of major depressive disorder in adult diabetic patients when data are examined across all age-groups. A secondary analysis was performed to assess this effect in younger and older subsets of patients. RESEARCH DESIGN AND METHODS: Younger (aged <55 years, n = 85) and older (aged > or =55 years, n = 67) subsets were identified from a multicenter, double-blind, placebo-controlled, maintenance treatment trial of sertraline in diabetic participants who achieved depression recovery with open-label sertraline treatment. Cox proportional hazards models were used to determine differences in time to depression recurrence between treatment arms (sertraline or placebo) for each age subset and between age subsets for each treatment. RESULTS: In younger subjects, sertraline conferred significantly greater prophylaxis against depression recurrence than placebo (hazard ratio 0.37 [95% CI 0.20-0.71]; P = 0.003). Benefits of sertraline maintenance therapy were lost in older participants (0.94 [0.39-2.29]; P = 0.89). There was no difference in time to recurrence for sertraline-treated subjects between age subsets (P = 0.65), but older subjects had a significantly longer time to recurrence on placebo than younger subjects (P = 0.03). CONCLUSIONS: While sertraline significantly increased the time to depression recurrence in the younger diabetic participants, there was no treatment effect in those aged > or =55 years because of a high placebo response rate. Further research is necessary to determine the mechanisms responsible for this effect and whether depression maintenance strategies specific for older patients with diabetes should be developed.

Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial.

CONTEXT: In patients with diabetes mellitus, depression is a prevalent and recurrent problem that adversely affects the medical prognosis. OBJECTIVE: To determine whether maintenance therapy with sertraline hydrochloride prevents recurrence of major depression in patients with diabetes. DESIGN: A randomized, double-blind, placebo-controlled, maintenance treatment trial. Patients who recovered from depression during open-label sertraline treatment continued to receive sertraline (n = 79) or placebo (n = 73) and were followed up for up to 52 weeks or until depression recurred. SETTING: Outpatient clinics at Washington University, St Louis, MO, the University of Washington, Seattle, and the University of Arizona, Tucson. PATIENTS: One hundred fifty-two patients with diabetes (mean age, 52.8 years; 59.9% female; 82.9% with type 2 diabetes) who recovered from major depression (43.3% of those initially assigned) during 16 weeks of open-label treatment with sertraline (mean dose, 117.9 mg/d). INTERVENTION: Sertraline continued at recovery dose or identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was length of time (measured as the number of days after randomization) to recurrence of major depression as defined in DSM-IV. The secondary outcome was glycemic control, which was assessed via serial determinations of glycosylated hemoglobin levels. RESULTS: Sertraline conferred significantly greater prophylaxis against depression recurrence than did placebo (hazard ratio = 0.51; 95% confidence interval, 0.31-0.85; P = .02). Elapsed time before major depression recurred in one third of the patients increased from 57 days in patients who received placebo to 226 days in patients treated with sertraline. Glycosylated hemoglobin levels decreased during the open treatment phase (mean +/- SD glycosylated hemoglobin level reduction, -0.4% +/- 1.4%; P = .002). Glycosylated hemoglobin levels remained significantly lower than baseline during depression-free maintenance (P = .002) and did not differ between treatment groups (P = .90). CONCLUSIONS: In patients with diabetes, maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression. Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year.

Early-stage Alzheimer disease represents increased suicidal risk in relation to later stages.

The level of risk for suicide in individuals with Alzheimer disease (AD) generally is considered to be low. It is important to recognize, however, that suicide can occur in early-stage Alzheimer disease on the background of a distinct high-risk profile. The objective of this report is to describe the clinical profiles of individuals with very mild Alzheimer disease who either attempted or completed suicide. We describe two participants in a longitudinal study of early-stage Alzheimer disease who were in the ninth decade of life and had very mild Alzheimer disease. Consistent with earlier cases reported in the literature, both displayed the following high-risk phenotype predisposing to suicidal risk: male gender, highly educated professional, preserved insight, dysthymic symptoms that did not meet criteria for major depression and post-dated the onset of cognitive decline, and suicidal ideation. Neuropathological examination confirmed histologic Alzheimer disease in both cases. These cases, taken together, emphasize the need for awareness that early-stage Alzheimer disease may present a unique suicidal risk compared with later stages.