Depression, the autonomic nervous system, and coronary heart disease

Depression is a risk factor for medical morbidity and mortality in patients with coronary heart disease (CHD). Dysregulation of the autonomic nervous system (ANS) may explain why depressed patients are at increased risk. Studies of medically well, depressed psychiatric patients have found elevated levels of plasma catecholamines and other markers of altered ANS function compared with controls. Studies of depressed patients with CHD have also uncovered evidence of ANS dysfunction, including elevated heart rate, low heart rate variability, exaggerated heart rate responses to physical stressors, high variability in ventricular repolarization, and low baroreceptor sensitivity. All of these indicators of ANS dysfunction have been associated with increased risks of mortality and cardiac morbidity in patients with CHD. Further research is needed to determine whether ANS dysfunction mediates the effects of depression on the course and outcome of CHD, and to develop clinical interventions that improve cardiovascular autonomic regulation while relieving depression in patients with CHD.     

Change in heart rate and heart rate variability during treatment for depression in patients with coronary heart disease

OBJECTIVE: Major depression is a common problem in patients with coronary heart disease (CHD) and is associated with an increased risk for cardiac morbidity and mortality. It is not known whether treating depression will improve medical prognosis in patients with CHD. Depression is also associated with elevated heart rate and reduced heart rate variability (HRV), which are known risk factors for cardiac morbidity and mortality that may explain the increased risk associated with depression. The purpose of this study was to determine whether treatment for depression with cognitive behavior therapy (CBT) is associated with decreased heart rate or increased HRV. METHODS: Thirty depressed patients with stable CHD, classified as either mildly or moderately to severely depressed, received up to 16 sessions of CBT. The 24-hour heart rate and HRV were measured in these patients and in 22 medically comparable nondepressed controls before and after treatment of the depressed patients. RESULTS: Average heart rate and daytime rMSSD (reflecting mostly parasympathetic activity) improved significantly in the severely depressed patients, but remained unchanged in the mildly depressed and the control patients. However, only rMSSD improved to a level comparable to the control patients. None of the remaining indices of HRV showed improvement. CONCLUSIONS: The results suggest that treating depression with CBT may reduce heart rate and increase short-term HRV. Thus, CBT may have a beneficial effect on a risk factor for mortality in depressed patients with coronary heart disease. A randomized, controlled study is needed to confirm these findings.     

Treatment of depression in cancer patients is associated with better life adaptation: a pilot study

Major depression occurs in a significant number of cancer patients, and there is evidence that cancer patients with depression do not receive adequate antidepressant treatment. In an uncontrolled pilot study, the authors assess the degree of depression and the quality of life after the initiation of antidepressant medication treatment in 12 depressed cancer patients who received adequate antidepressant drugs and in 10 depressed cancer patients who received inadequate antidepressant treatment. These preliminary findings suggest that cancer patients with major depression benefit from antidepressant medication treatment and may experience an improved psychosocial adjustment to cancer. Controlled clinical trials will be necessary to verify these preliminary findings.     

Interpersonal psychotherapy as augmentation treatment in depressed elderly responding poorly to antidepressant drugs: a case series

BACKGROUND: Medication is often the first choice in the treatment of depression, even though large numbers of depressed patients do not respond to antidepressant drugs or fail to achieve symptom remission or recovery. Generally, other drugs, rather than other therapeutic approaches such as psychotherapy, are used as augmentation treatment. This applies in particular to elderly patients. The aim of this work is to assess whether augmentation with interpersonal psychotherapy (IPT) can bring about symptom remission in depressed elderly responding poorly to medication. METHOD: Five cognitively intact patients aged over 60 and suffering from major depression were first treated for 6 weeks with a selective serotonin reuptake inhibitor compound. Owing to poor outcome, IPT was added to the treatment. IPT is a brief psychotherapy addressing the interpersonal problems linked to depression, and has been modified for use with elderly patients. RESULTS: All patients achieved symptom remission after a cycle of psychotherapy lasting a minimum of 16 and a maximum of 20 weekly sessions. CONCLUSIONS: The methodological limitations of this open study do not allow us to generalize from the positive outcomes. Further studies might confirm these initial observations and establish whether an equally satisfactory therapeutic response can be attained if medication is discontinued after the start of psychotherapy.     

Influence of resistance to antidepressant pharmacotherapy on short-term response to electroconvulsive therapy

BACKGROUND: Few studies assessing the influence of resistance to antidepressant pharmacotherapy on the response to subsequent electroconvulsive therapy (ECT) are found in the literature. Results are somewhat conflicting and may not be applicable to the population of depressed patients in The Netherlands. The aim of this study is to assess the influence of medication resistance on the short-term response to ECT in a population of severely depressed inpatients in The Netherlands, where ECT is an exceptional treatment, often used as a final treatment option. METHODS: We reviewed the records of 41 consecutive inpatients with major depression according to DSM-III-R criteria and rated each patients' antidepressant pharmacotherapy prior to ECT. We examined the extent to which medication resistance was related to short-term response to ECT. RESULTS: When a reduction of at least 50% on the Hamilton Rating Scale for Depression (HRSD) post-ECT compared to pre-ECT (partial remission) is used as response criterion, medication resistant patients and patients without established medication resistance were equally likely to respond to subsequent ECT. When a post-ECT HRSD score < or = 7 (full remission) is used as response criterion, medication resistant patients were less likely to respond to subsequent ECT (8/29=27.6%) than patients who did not receive adequate antidepressant pharmacotherapy prior to ECT (6/12=50.0%), although the difference in response rate was not statistically significant. LIMITATIONS: This study has a retrospective nature and a relatively small sample size. CONCLUSION: Antidepressant medication resistance does not seem to have an influence on the short-term response to subsequent ECT. However, when the number of patients achieving full remission is concerned, a substantial percentage of antidepressant medication resistant patients respond to ECT, although their response rate was nearly half compared to that of patients without prior adequate treatment with antidepressants. This difference in response rate was not statistically significant. ECT seems to be an effective treatment for both patients with and without prior adequate treatment with antidepressants in this Dutch population.     

Alteration of cardiac autonomic functions in patients with major depression: a study using heart rate variability measures

BACKGROUND: Depression is associated with greater cardiac morbidity and mortality. One of the contributory factors for this may be altered cardiac autonomic activity in depression. However, cardiac autonomic involvement in depression remains controversial because of methodological issues. In this study, alteration of cardiac autonomic functions was studied in drug-naive patients with major depression without co-morbidity. Heart rate variability, a sensitive measure of neurocardiac autonomic regulation was used in addition to conventional methods of measuring cardiac autonomic functions. METHODS: We recruited 40 patients suffering from major depression, diagnosed based on DSM-IV-TR criteria. Their cardiac autonomic functions were measured using both conventional and heart rate variability measures. These were compared with those of age- and gender-matched healthy controls. RESULTS: Patients with major depression showed significantly lesser Valsalva ratio, maximum/minimum ratio and greater sympathovagal balance than healthy controls indicating decreased parasympathetic and increased sympathetic activity. CONCLUSIONS: Depression is associated with alteration of cardiac autonomic tone towards decreased parasympathetic activity and an increased sympathetic activity. It is possible that a common neurobiological dysfunction contributes to both depression and cardiac autonomic changes in the illness.     

Motor activity and autonomic cardiac functioning in major depressive disorder

BACKGROUND: The daily pattern of motor activity and the autonomic cardiovascular regulation were studied in major depression to quantify changes in psychomotor function and autonomic cardiac functioning. Additionally, relationships between motor activity parameters, cardiovascular measures and specific clinical features were examined. METHODS: Wrist-actigraphy was used to monitor 24-h motor activity for 67 unmedicated (unipolar) depressed inpatients and 64 control subjects. During supine rest, spectral analysis was applied to assess HR and SBP variability, a baroreflex sensitivity (BRS) index and the respiratory frequency, in addition to mean heart rate (HR) and blood pressure (BP) levels for the patient group and a second control group (N=51). RESULTS: The patients showed a lower motor activity level and a reduced fragmentation of motor activity during wake, and a higher motor activity level and a decreased immobility during sleep. The mean HR and DBP level and the respiratory frequency were higher in the patient group than in the control group, but no differences in HR and SBP variability or BRS were found. Furthermore, motor activity parameters and cardiovascular measures of the patients were related to agitation and retardation and overall, patients with lower motor activity levels demonstrated lower SBP levels. CONCLUSIONS: This study confirms that the 24-h pattern of motor activity is altered in unmedicated depressed inpatients, but limited evidence was found for an autonomic cardiac dysfunction. Within the patient group there were relationships between motor activity parameters, cardiovascular measures, and clinical features, but the underlying neurobiological pathways need to be further explored.     

One size fits some: the impact of patient treatment attitudes on the cost-effectiveness of a depression primary-care intervention

BACKGROUND: Despite their impact on outcomes, the effect of patient treatment attitudes on the cost-effectiveness of health-care interventions is not widely studied. This study estimated the impact of patient receptivity to antidepressant medication on the cost-effectiveness of an evidence-based primary-care depression intervention. METHOD: Twelve community primary-care practices were stratified and then randomized to enhanced (intervention) or usual care. Subjects included 211 patients beginning a new treatment episode for major depression. At baseline, 111 (52.6%) and 145 (68.7%) reported receptivity to antidepressant medication and counseling respectively. The intervention trained the primary-care teams to assess, educate, and monitor depressed patients. Twelve-month incremental (enhanced minus usual care) total costs and quality-adjusted life years (QALYs) were calculated. RESULTS: Among patients receptive to antidepressants, the mean incremental cost-effectiveness ratio was dollar 5,864 per QALY (sensitivity analyses up to dollar 14,689 per QALY). For patients not receptive to antidepressants, the mean incremental QALY score was negative (for both main and sensitivity analyses), or the intervention was at least no more effective than usual care. CONCLUSIONS: These findings suggest a re-thinking of the 'one size fits all' depression intervention, given that half of depressed primary-care patients may be non-receptive to antidepressant medication treatment. A brief assessment of treatment receptivity should occur early in the treatment process to identify patients most likely to benefit from primary-care quality improvement efforts for depression treatment. Patient treatment preferences are also important for the development, design, and analysis of depression interventions.     

Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression

Antidepressant medication is considered the current standard for severe depression, and cognitive therapy is the most widely investigated psychosocial treatment for depression. However, not all patients want to take medication, and cognitive therapy has not demonstrated consistent efficacy across trials. Moreover, dismantling designs have suggested that behavioral components may account for the efficacy of cognitive therapy. The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a randomized placebo-controlled design in adults with major depressive disorder (N = 241). In addition, it examined the importance of initial severity as a moderator of treatment outcome. Among more severely depressed patients, behavioral activation was comparable to antidepressant medication, and both significantly outperformed cognitive therapy. The implications of these findings for the evaluation of current treatment guidelines and dissemination are discussed.     

P300 changes in major depressive disorders with and without psychotic features

BACKGROUND: Although there are many P300 studies in depressive patients, only a few studies have focused on the effects of psychotic features in depression and of response to antidepressant treatment on P300. This study was designed to investigate possible differences in the P300 component of event-related potentials in depressed patients with and without psychotic features and if any, to see whether these changes altered with treatment of depression. METHODS: Thirty-six patients with major depressive disorder diagnosed according to DSM-IV, and 20 healthy control subjects were involved in the study. Sixteen of the patients had psychotic features. Auditory P300 was recorded before treatment and after remission. RESULTS: Pretreatment P300 latencies were significantly prolonged both in patients with and without psychotic features compared to controls. Pretreatment P300 amplitudes were significantly decreased only in the patients with psychotic features. After treatment of depression, delayed P300 latencies in both patient groups and decreased P300 amplitude in the patient group with psychotic features were normalized. LIMITATIONS: The medication status of the patient was heterogeneous. CONCLUSION: Since the impairment seems to be improved by drug treatment, prolonged P300 latency might be a state marker for a major depressive episode, and decreased P300 amplitude which is correlated with paranoid ideation might be more associated with psychotic subtype.     

Treatment of Depression in Multiple Sclerosis: Review and Meta-analysis

The aim of this article is to review the results of outcome studies of the treatment of depression in patients with multiple sclerosis (MS) using meta-analysis. All treatments for depression in MS were found to be significantly more effective than no treatment. Patients in control groups that received no treatment, as opposed to minimal treatment, tended to become more depressed over time, suggesting that untreated depression worsens without treatment. There appears to be no significant difference in efficacy between psychotherapy and antidepressant medication. Psychothera-pies that focus on improving coping skills are more effective at reducing depression than psychotherapies that focus on increasing insight. We conclude that patients with MS should be evaluated routinely for depression. Patients reporting symptoms of depression should be referred for treatment since active intervention is effective at reducing depression and untreated symptoms are likely to worsen.     

Treatment response in late-onset depression: relationship to neuropsychological, neuroradiological and vascular risk factors

BACKGROUND: Late-onset depressive disorder is associated with white matter lesions and neuropsychological deficits that in some studies are linked to a poorer outcome for depression. Some white matter lesions may be vascular in origin. This study investigated the relationship between response or non-response to antidepressant monotherapy and neuropsychological function, structural brain measures and vascular factors. METHOD: This was a case control study. Fifty patients with late-onset major depressive disorder (29 who were responders to antidepressant monotherapy and 21 who were not) were compared with 35 non-depressed control subjects. Measures included assessment of vascular risk factors, neuropsychological testing and a magnetic resonance imaging (MRI) scan. RESULTS: After adjustment for depressed mood and medication at evaluation, both patient groups had significantly more impairment compared to control subjects on verbal learning tasks involving immediate or delayed recall. Patients who did not respond to antidepressant monotherapy had significantly poorer performance than controls on tests involving visuospatial ability, language, word recognition and tests of executive function, whereas there were no differences between control subjects and responders. On two tests of executive function (verbal fluency and the Stroop test) non-responders scored significantly worse than responders. There were no significant group differences on MRI measures of atrophy or of white matter lesions apart from a higher periventricular hyperintensity score in non-responders compared to controls. There were no group differences on measures of vascular disease. CONCLUSION: The results lend support to the emerging evidence that resistance to treatment in late-onset depression may be associated with impaired executive function. Subtle cerebrovascular mechanisms may be involved.     

Evidence of an early information processing speed deficit in unipolar major depression

BACKGROUND: Slowing of the speed of information processing has been reported in geriatric depression, but it is not clear if the impairment is present in younger patients, if motor retardation is responsible, or if antidepressant medications play a role. METHOD: Twenty unmedicated unipolar depressed inpatients were compared with 19 medicated depressed in-patients and 20 age-, sex- and verbal IQ-matched controls on inspection time (IT), a measure of speed of information processing that does not require a speeded motor response. We also examined the relationship between IT and current mood and length of depressive illness. RESULTS: Unmedicated depressed patients showed slowing of information processing speed when compared to both medicated depressed patients and controls. The latter two groups were not significantly different from each other. Slowing of IT was not associated with current mood, but was negatively correlated with length of illness since first episode. No differences in IT were found between patients receiving medication with anticholinergic effects and patients receiving medication with no anticholinergic effects. CONCLUSIONS: The findings indicate that unipolar depression is associated with a slowing of speed of information processing in younger patients who have not received antidepressant medication. This does not appear to be a result of motor slowing.     

中重度抑郁症患者心电图及心率变异性分析

目的:探讨中重度抑郁症患者心电图及心率变异性特点,为临床评估中重度抑郁症心脏自主神经功能变化提供依据.方法:选择2018年6月至2019年12月就诊于湖南省脑科医院的中重度抑郁症患者38例为研究组,32例健康志愿者为对照组,比较两组心电图异常率及心率变异性,并统计分析各指标之间的差异.结果:研究组心电图异常ST-T改变...     

Autonomic neurocardiac function in patients with major depression and effects of antidepressive treatment with nefazodone

BACKGROUND: Major depression (MD) is associated with an augmented risk of cardiovascular mortality. One possible explanation for this association is that MD influences autonomic neurocardiac regulation (ANR). However, previous studies on this subject revealed conflicting results. METHODS: Using an autonomic test battery, which consisted of standardised measurements of heart rate variability (HRV) and blood pressure, we (1) compared ANR between 25 patients with DSM-III-R diagnosed MD and 60 healthy controls, and (2) investigated the autonomic effects of antidepressive treatment with nefazodone. RESULTS: Following multivariate analysis of all tests a significant reduction in HRV could only be shown for the Valsalva ratio amongst the depressives compared to controls. There was a significant inverse correlation between the HRV during deep respiration and both the severity of depression and the duration of the depressive episode. Serial HRV recordings revealed that both the mean resting heart rate and systolic blood pressure significantly decreased after 21 days of nefazodone treatment (average dosage 413 mg/day), whereas after 10 days (average dosage 270.8 mg/day) there were no striking changes compared to the pre-treatment values. During nefazodone treatment no significant changes in parasympathetic tone occurred. LIMITATIONS: ANR was not assessed in a randomised, placebo-controlled fashion. CONCLUSIONS: (1) Patients with MD may suffer from functional disturbances in the interaction between the sympathetic and parasympathetic autonomic tree. (2) The pattern of autonomic changes during treatment suggests that nefazodone induced a dose dependent, serotonergically-mediated down-regulation of the sympathetic tone. This mechanism might be responsible for nefazodone's properties of reducing anxiety.     

A novel neurological mechanism to explain the adverse effect of depression on coronary artery disease

The strong antecedent effect of depression as a risk factor in the development of coronary artery disease (CAD) has been demonstrated in many robust epidemiological studies. However, the underlying causative mechanisms are incompletely understood: this hypothesis proposes one possibility. A variety of histological and radiological techniques have been used to demonstrate structural and functional abnormalities in the prefrontal cortex (PFC) of depressed subjects. In addition, this limbic region has been inextricably implicated in the modulation of autonomic tone. Cardio-specifically, stimulation of PFC has arrhythmogenic effects. Reciprocally, cardiac stress tests produce activation of this cortical region. These observations place PFC at the top of a hierarchical autonomic loop involved in sensing and modulating cardiac variables. Finally, the reduced heart rate variability, higher heart rates and elevated cerebrospinal fluid catecholamine levels in depressed patients, compared to non-depressed matched controls, suggest sympathetic overdrive in these patients. These observations lead the author to propose that a primary defect in the PFC of depressed subjects destabilises the autonomic neurocardiac axis, accounting for the proven adverse effect of depression on CAD. This novel neurological mechanism can help to develop other current theories and to design and trial future therapies to reduce the adverse effect of depression on coronary artery disease.     

The depression-pain syndrome and its response to antidepressants

In an attempt to elucidate the relationship between depression and pain, the authors studied 300 pain center patients; 261 (87%) of these patients referred for diagnosis and treatment of their pain syndromes were depressed. In another study of 196 private patients with depression, 116 (59%) also had recurring benign pain. When treated with antidepressant medications, 96 of these 116 (83%) obtained significant relief of their pain syndromes. The frequency with which antidepressants can significantly alleviate pain associated with depression highlights the importance of the link between pain and depression, which may be partially explained by the close relationship of enkephalins and biogenic amines     

Pharmacologic treatment of depression in patients with heart disease

The relationship between depression and cardiovascular disease is complex and multifaceted. There is a growing body of evidence that depression significantly and adversely affects cardiovascular health. Perhaps the most prominent finding is the documented increase in mortality rate in patients with depression after myocardial infarction. The critical questions of interest to both the clinician and researcher are whether there are safe and effective treatments for depression in patients with heart disease and whether treatment of depression reduces the increased risk of cardiac morbidity and mortality. Although the data are limited and are primarily from open or comparator trials, the tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRI) are effective for treatment of depression in patients with ischemic heart disease (IHD), and response rates are comparable with those reported in depressed patients without heart disease. In terms of safety, the TCAs are associated with documented adverse cardiovascular effects, including increases in heart rate, orthostatic hypotension, and conduction delays. Use of TCAs in patients with IHD carries a proven increased risk of cardiac morbidity and perhaps of mortality as well. The SSRI appear to be relatively safe and effective in the treatment for depression in patients with comorbid IHD.     

Use of tricyclic antidepressants in recipients of heart transplants

Cardiac transplantation has become an accepted treatment for certain endstage cardiac disease patients. Depression and significant psychosocial stress among heart transplant recipients are not uncommon, but published reports about the use of antidepressants in these persons are very rare. The authors of this study report on a group of nine heart transplant recipients treated with antidepressant medicines. Seven patients achieved clinical remissions of their depression, and only two were unable to tolerate the noncardiac side effects of the medication. Indicators of autonomic, electrocardiographic, and hemodynamic functions showed no adverse effects. Although the study is based on a small sample, it appears that tricyclic antidepressants are safe and effective in heart transplant recipients.     

Antidepressant treatment improves adherence to antiretroviral therapy among depressed HIV-infected patients

BACKGROUND: Antiretroviral regimens for HIV-infected patients require strict adherence. Untreated depression has been associated with medication nonadherence. We proposed to evaluate the effect of antidepressant treatment (ADT) on antiretroviral adherence. METHODS: Data were retrieved for HIV-infected patients seen at an urban health care setting (1997-2001) from chart review and administrative and pharmacy files. Antiretroviral adherence was determined for depressed patients stratified by receipt of and adherence to ADT. Antiretroviral adherence was compared before and after initiation of ADT. RESULTS: Of 1713 HIV-infected patients, 57% were depressed; of those, 46% and 52% received ADT and antiretroviral treatment, respectively. Antiretroviral adherence was lower among depressed patients not on ADT (vs. those on ADT; P = 0.012). Adherence to antiretroviral treatment was higher among patients adherent to ADT (vs. those nonadherent to antidepressant treatment; P = 0.0014). Antiretroviral adherence improved over a 6-month period for adherent, nonadherent, and nonprescribed ADT groups; however, the mean pre- versus post-6-month change in antiretroviral adherence was significantly greater for those prescribed antidepressants. CONCLUSIONS: Depression was common, and antiretroviral adherence was higher for depressed patients prescribed and adherent to ADT compared with those neither prescribed nor adherent to ADT. Attention to diagnosis and treatment of depressive disorders in this population may improve antiretroviral adherence and ultimate survival.