Impact of medical comorbid disease on antidepressant treatment of major depressive disorder

A major factor in evaluating and treating depression is the presence of comorbid medical problems. In this paper, the authors will first evaluate studies showing that medical illness is a risk factor for depression. The authors will review a series of randomized, controlled studies of antidepressant treatment in subjects with major depressive disorder (MDD) and comorbid medical illnesses (myocardial infarction, stroke, diabetes, cancer, and rheumatoid arthritis). Most of these studies report an advantage for an active antidepressant over placebo in improvement of depressive symptoms. The authors also will review a series of studies in which the outcome of antidepressant treatment is compared between subjects with MDD with and without comorbid medical illness. In these studies, subjects with medical illness tend to have lower improvement of depressive symptoms and higher rates of depressive relapse with antidepressant treatment compared with MDD subjects with no medical comorbidity. In addition, the authors will review hypotheses on the mechanism of the interaction between medical illness and clinical response in MDD. The paper will conclude that medical comorbidity is a predictor of treatment resistance in MDD.     

Clinical and health services relationships between major depression, depressive symptoms, and general medical illness.

Patients with chronic medical illness have a high prevalence of major depressive illness. Major depression may decrease the ability to habituate to the aversive symptoms of chronic medical illness, such as pain. The progressive decrements in function associated with many chronic medical illnesses may cause depression, and depression is associated with additive functional impairment. Depression is also associated with an approximately 50% increase in medical costs of chronic medical illness, even after controlling for severity of physical illness. Increasing evidence suggests that both depressive symptoms and major depression may be associated with increased morbidity and mortality from such illnesses as diabetes and heart disease. The adverse effect of major depression on health habits, such as smoking, diet, over-eating, and sedentary lifestyle, its maladaptive effect on adherence to medical regimens, as well as direct adverse physiologic effects (i.e., decreased heart rate variability, increased adhesiveness of platelets) may explain this association with increased morbidity and mortality.     

Paroxetine for somatic pain associated with physical illness: a review

Objective: The purpose of this article is to review the prevalence of somatic pain with and without depression or anxiety and the pharmacologic effects of the selective serotonin reuptake inhibitor paroxetine on pain in physical conditions with and without comorbid depression or anxiety. Data Sources: MEDLINE and PsychLIT/PsycINFO database. Keywords included depression, anxiety, pain, somatic, antidepressants, and paroxetine. Only English-language publications and abstracts were considered. Study Selection: More than 100 articles that reflected the prevalence of somatic pain in patients with physical illness with and without comorbid depression or anxiety and that evaluated the efficacy of antidepressants in this population were identified and reviewed. Data Synthesis: Nearly two thirds of patients with major depressive disorder suffer from a physical illness, and about one fifth of patients with chronic physical illness are depressed. Both of these comorbidities pose diagnostic and therapeutic challenges. Therapeutic effects of antidepressants on pain improvement in patients with chronic physical illnesses and comorbid depression/anxiety have been attributed to the antidepressant or anxiolytic properties of these drugs. However, tricyclic antidepressants have demonstrated analgesic properties in patients with physical illness both with and without depression. The review looks at evidence for the efficacy of the selective serotonin reuptake inhibitor paroxetine on pain in physical illness with and without depression and the mechanisms for the relief of pain and depression. Conclusions: The efficacy of paroxetine for depression and anxiety comorbid with physical illness looks promising. Studies also allude to evidence linking the analgesic properties of paroxetine with its serotonergic and noradrenergic activity. Large randomized controlled trials within specific antidepressant classes and also comparing dualaction antidepressants are warranted that could shed some light on the unique advantage of paroxetine over other antidepressants.     

Diagnosis and management of bipolar disorder with comorbid anxiety in the elderly

Currently, in individuals over 65 year of age, prevalence rates of bipolar disorder range from 0.1% to 0.4%. As is the case for bipolar disorder in younger individuals, bipolar disorder may be unrecognized or underrecognized among older adults. While anxiety disorders are frequently comorbid among younger individuals with bipolar illness, the prevalence and impact of comorbid anxiety is far less understood among geriatric individuals with bipolar disorder, in whom anxiety disorders may be underreported. This comorbidity may have serious consequences, since in older adult populations with depression, the presence of comorbid anxiety is associated with more severe depressive symptoms, more chronic medical illness, greater functional impairment, and lower quality of life; the same associations may prove to be true in older patients with bipolar disorder. As with younger individuals with bipolar disorder, effective treatment of the underlying mood disorder is critically important before treating comorbid symptoms. Unfortunately, few evidence-based studies are available to guide the treating clinician in the management of these vulnerable patients, many of whom have additional psychiatric or medical comorbidity.     

Depression, fatigue, and functional disability in patients with chronic hepatitis C

OBJECTIVE: To examine the extent to which fatigue and functional disability correlate with severity of depressive symptoms in patients with chronic hepatitis C. METHODS: Fifty patients with chronic hepatitis C were evaluated using structured psychiatric interviews and standardized rating instruments. RESULTS: Fourteen (28%) of patients had current depressive disorders. Depressed and nondepressed patients did not differ with regard to demographics or hepatic disease severity. Severity of depressive symptoms was highly correlated with fatigue severity while measures of hepatic disease severity, interferon treatment, and severity of comorbid medical illness were not. Severity of depressive symptoms was associated with functional disability and somatization. CONCLUSIONS: Disability and fatigue are more closely related to depression severity than to hepatic disease severity. Antidepressant treatment trials in patients with hepatitis C are indicated to determine whether improvement in depressive symptoms leads to improvement in fatigue and functioning.     

Comorbid anxiety disorders in depressed elderly patients

OBJECTIVE: Anxiety disorders are common in adults with depressive disorders, but several studies have suggested a relatively low prevalence of anxiety disorders in older individuals with depression. This cross-sectional study measured current and lifetime rates and associated clinical features of anxiety disorders in depressed elderly patients. METHOD: History of anxiety disorders was assessed by using a structured diagnostic instrument in 182 depressed subjects aged 60 and older seen in primary care and psychiatric settings. Associations between comorbid anxiety disorders and baseline characteristics were measured. The modified structured instrument allowed detection of symptoms that met inclusion criteria for generalized anxiety disorder in a depressive episode. RESULTS: Thirty-five percent of older subjects with depressive disorders had at least one lifetime anxiety disorder diagnosis, and 23% had a current diagnosis. The most common current comorbid anxiety disorders were panic disorder (9.3%), specific phobias (8.8%), and social phobia (6.6%). Symptoms that met inclusion criteria for generalized anxiety disorder, measured separately, were present in 27.5% of depressed subjects. Presence of a comorbid anxiety disorder was associated with poorer social function and a higher level of somatic symptoms. Symptoms of generalized anxiety disorder were associated with a higher level of suicidality. CONCLUSIONS: Contrary to previous reports, the present study found a relatively high rate of current and lifetime anxiety disorders in elderly depressed individuals. Comorbid anxiety disorders and symptoms of generalized anxiety disorder were associated with a more severe presentation of depressive illness in elderly subjects.     

Psychological correlates of functional status in chronic fatigue syndrome

Background: The present study was designed to test a cognitive model of impairment in chronic fatigue syndrome (CFS) in which disability is a function of severity of fatigue and depressive symptoms, generalized somatic symptom attributions and generalized illness worry. Methods: We compared 45 CFS and 40 multiple sclerosis (MS) outpatients on measures of functional ability, fatigue severity, depressive symptoms, somatic symptom attribution and illness worry. Results: The results confirmed previous findings of lower levels of functional status and greater fatigue among CFS patients compared to a group of patients with MS. Fatigue severity was found to be a significant predictor of physical functioning but not of psychosocial functioning in both groups. In CFS, when level of fatigue was controlled, making more somatic attributions was associated with worse physical functioning, and both illness worry and depressive symptoms were associated with worse psychosocial functioning. Conclusions: Our findings support the role of depression and illness cognitions in disability in CFS sufferers. Different cognitive factors account for physical and psychosocial disability in CFS and MS. The SF-36 may be sensitive to symptom attributions, suggesting caution in its interpretation when used with patients with ill-defined medical conditions.     

Treating depression complicated by comorbid medical illness or anxiety

In this online activity, Trivedi discusses pharmacotherapy treatments for depression in the presence of comorbid medical illness or physical symptoms. The focus is on key aspects of treatment such as remission as the treatment goal, effects of different classes of antidepressants, and benefits of using treatment algorithms. Clayton addresses issues related to comorbid depression and anxiety including prevalence and recognition, risk factors and outcomes, and treatment considerations. Frank highlights the importance of psychotherapy in the treatment of complicated depression, citing empirically validated psychotherapies for acute depressive episodes as well as describing how to apply psychotherapy to medical patients with depression.     

Somatic symptoms of depression in elderly patients with medical comorbidities

OBJECTIVE: Somatic symptoms of depression such as fatigue create a diagnostic dilemma when assessing an older patient with medical comorbidities, since chronic medical illnesses may produce similar symptoms. Alternatively, somatic symptoms attributed to medical illness may actually be caused by depression. These analyses were designed to determine if somatic symptoms in older patients are more strongly associated with chronic physical problems or with depression. DESIGN: Reanalysis of data from an observational study of depression in primary care and a randomized trial of paroxetine and nortriptyline for the treatment of major depression. Patients were evaluated with a structured diagnostic interview and a battery of psychiatric, physical, and psychosocial measures. PARTICIPANTS: Two hundred and forty eight primary care and psychiatric patients aged >or= 60 years. METHODS: Associations among depression, somatization, and chronic physical problems were examined using correlations and regression modeling. RESULTS: Two somatization measures, the Asberg Side Effects Rating Scale and the Utvalg for Kliniske Undersogelser (UKU), were significantly associated with psychological symptoms of depression (r = 0.73 and r = 0.76, p < 0.0001) but not with medical comorbidities (r = 0.02, p = 0.16 and r = 0.10, p = 0.78). In multiple regression models, psychological symptoms of depression remained significant predictors of somatization (p < 0.0001) after controlling for age, gender, and medical comorbidities. CONCLUSIONS: In older patients with medical disorders and multiple somatic complaints, clinicians should consider the possibility of depression. Rating scales emphasizing somatic symptoms associated with depression may provide a more accurate measure of depression severity than those excluding such symptoms.     

Follow-up and family study of anxious depression

OBJECTIVE: The failure of the concept of anxious depression to find its way into DSM-III-R led the authors to conclude that a further report on the occurrence of anxiety symptoms in depressed subjects is indicated. METHOD: The subjects were 327 consecutively evaluated inpatients and outpatients with primary unipolar depressive disorder at five university medical centers participating in the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression--Clinical Studies. The authors restricted their sample selection to patients with primary depressive disorder so that patients with other preexisting psychiatric disorders, especially anxiety disorders, would not contaminate the symptom picture, family studies, or follow-up. The examined six anxiety symptoms and derived a new anxiety summary score to show the effect of anxiety in depression on family data and 5-year outcome. RESULTS: Depressed subjects with higher ratings for anxiety took longer to recover. There was also a significant relationship between anxiety in depressed probands and the risk for primary unipolar depressive disorder, but not anxiety disorders or alcoholism, among 832 blindly interviewed first-degree relatives. CONCLUSIONS: These data confirm the usefulness of subdividing depressed patients according to anxiety symptoms: psychic and somatic symptoms of anxiety, taken together, significantly predict family illness and course. The data also emphasize the wisdom of requiring that generalized anxiety disorder not be diagnosed in the presence of a mood disorder. Clearly, symptoms of anxiety coexist with depression and need to be recognized for the effective treatment of the underlying depressive disorder.     

Patients presenting with somatic complaints: epidemiology,psychiatric comorbidity and management

Somatic symptoms are the leading cause of outpatient medical visits and also the predominant reason why patients with common mental disorders such as depression and anxiety initially present in primary care. At least 33% of somatic symptoms are medically unexplained, and these symptoms are chronic or recurrent in 20% to 25% of patients. Unexplained or multiple somatic symptoms are strongly associated with coexisting depressive and anxiety disorders. Other predictors of psychiatric co-morbidity include recent stress, lower self-rated health and higher somatic symptom severity, as well as high healthcare utilization, difficult patient encounters as perceived by the physician, and chronic medical disorders. Antidepressants and cognitive-behavioural therapy are both effective for treatment of somatic symptoms, as well as for functional somatic syndromes such as irritable bowel syndrome, fibromyalgia, pain disorders, and chronic headache. A stepped care approach is described, which consists of three phases that may be useful in the care of patients with somatic symptoms.     

Medical conditions and depressive,anxiety, and somatic symptoms in older adults with and without generalized anxiety disorder

Objective: The objective of this study was to examine medical illness and anxiety, depressive, and somatic symptoms in older medical patients with generalized anxiety disorder (GAD).

Method: A case-control study was designed and conducted in the University of California, San Diego (UCSD) Geriatrics Clinics. A total of fifty-four older medical patients with GAD and 54 matched controls participated.

Measurements: The measurements used for this study include: Brief Symptom Inventory–18, Mini International Neuropsychiatric Interview, and the Anxiety Disorders Interview Schedule.

Results: Older medical patients with GAD reported higher levels of somatic symptoms, anxiety, and depression than other older adults, as well as higher rates of diabetes and gastrointestinal conditions. In a multivariate model that included somatic symptoms, medical conditions, and depressive and anxiety symptoms, anxiety symptoms were the only significant predictors of GAD.

Conclusion: These results suggest first, that older medical patients with GAD do not primarily express distress as somatic symptoms; second, that anxiety symptoms in geriatric patients should not be discounted as a byproduct of medical illness or depression; and third, that older adults with diabetes and gastrointestinal conditions may benefit from screening for anxiety.     

Abnormal illness behavior of patients with functional somatic symptoms: relation to psychiatric disorders.

Functional somatic symptoms are highly associated with hypochondriasis, anxiety, and depressive disorders. Despite the absence of an organic disorder, underlying psychological distress of patients with functional somatic symptoms may result in abnormal illness behavior such as inadequate treatment seeking or overuse of medical services. Using the Illness Behavior Questionnaire (IBQ), we examined the illness behavior of Japanese patients visiting a general medicine clinic whose physical symptoms were considered functional. We used the General Health Questionnaire-30 to classify patients with functional somatic symptoms as those with and without psychological distress. Patients with distress (n=35) reported more physical complaints and higher IBQ scores than did patients without distress (n=22). The IBQ profile of patients with psychological distress was identical to that of patients diagnosed with either hypochondriasis or major depression. The illness behavior of patients without psychological distress was indistinguishable from that of patients whose physical symptoms were attributed to organic disease. These results further support the hypothesis that functional somatic symptoms may be associated with hypochondriasis and major depression, the pathology of which may contribute to the development of abnormal illness behavior.     

Medical illness and response to treatment in primary care panic disorder

OBJECTIVE: Although studies have suggested that comorbid medical illness can affect the outcome of patients with depression, little is known about whether medical illness comorbidity affects treatment outcome in patients with anxiety. METHOD: Primary care patients with panic disorder (n=232), participating in a randomized collaborative care intervention of CBT and pharmacology, were divided into those above (n=125) and below (n=107) the median for burden of chronic medical illness and assessed at 3, 6, 9 and 12 months. RESULTS: Subjects with a greater burden of medical illness were more psychiatrically ill at baseline, with greater anxiety symptom severity, greater disability and more psychiatric comorbidity. The intervention produced significant and similar increases in amount of evidence-based care, and reductions in clinical symptoms and disability that were comparable in the more and less medically ill groups. CONCLUSIONS: The comparable response of individuals with more severe medical illness suggests that CBT and pharmacotherapy for panic disorder work equally well regardless of medical illness comorbidity. However, the more severe psychiatric illness both at baseline and follow-up in these same individuals suggest that treatment programs may need to be extended in time to optimize treatment outcome.     

神经症与抑郁症的躯体化症状及经济损失比较

目的：比较神经症和抑郁症躯体症状的特点及经济损失。方法：对初次就诊的神经症和抑郁症患者，采用自编躯体症状的特点及经济负担调查问卷，调查躯体症状及经济损失状况。结果：二者躯体症状所占的比例差异无显著性，神经症组的病程显著长于抑郁症组，外院就诊次数也多于后组，从其他科至医学心理科就诊的时间间隔长。抑郁症组汉密尔顿焦虑量表（HAMA）精神焦虑因子分、汉密尔顿抑郁量表（HAMD）总分、体质量、认知障碍、日夜变化、阻滞、绝望感因子分均高于神经症组，焦虑／躯体化因子分低于神经症组。躯体症状组HAMA总分及躯体焦虑因子分、HAMD总分、焦虑／躯体化、体质量、睡眠障碍、绝望感因子分均高于无躯体症状组。神经症组的直接经济损失重于抑郁症组。结论：抑郁症、神经症的抑郁、焦虑、躯体症状的表现有各自特点，躯体症状会加重抑郁和焦虑症状，均造成很大的经济负担。     

Epidemiology of depression in primary care.

Major depressive disorder has been recently found to be associated with high medical utilization and more functional impairment than most chronic medical illnesses. Major depression is a common illness among persons in the community, in ambulatory medical clinics, and in inpatient medical care. Studies have estimated that major depression occurs in 2%-4% of persons in the community, in 5%-10% of primary care patients, and 10%-14% of medical inpatients. In each setting there are two to three times as many persons with depressive symptoms that fall short of major depression criteria. Recent studies have found that in one-third to one-half of patients with major depression, the symptoms persist over a 6-month to one-year period. The majority of longitudinal studies have determined that severity of initial depressive symptoms and the presence of a comorbid medical illness were predictors of persistence of depression.     

Improving the care for depression in patients with comorbid medical illness

OBJECTIVE: The authors compared treatment and outcomes for depressed primary care patients with and without comorbid medical conditions and assessed the impact of quality improvement programs for these patients. METHOD: The study group included 1,356 patients with major depression, dysthymia, or subthreshold depression from 46 managed primary care clinics. Clinics were randomly assigned depression treatment programs consisting of usual care for depression or one of two quality improvement programs for depression. The quality improvement programs included training experts and nurse specialists to provide education and assessment, plus access to nurse specialists for medication follow-up or access to psychotherapists. Outcomes were assessed at 6 and 12 months. RESULTS: At 6- and 12-month follow-up, the likelihood of having a probable depressive disorder was higher, but the rates of use of antidepressant medication and specialty counseling were similar, for depressed patients with comorbid medical disorders than for depressed patients who did not have comorbid medical disorders. Among the depressed patients with comorbid medical disorders, the combined quality improvement programs resulted in greater use of antidepressant medications and psychotherapy and lower rates of probable depressive disorders at both 6- and 12-month follow-up than did the usual care depression treatment program. CONCLUSIONS: Depressed patients with comorbid medical disorders tend to have similar rates of treatment but worse depression outcomes than depressed patients without comorbid medical illness. Quality improvement programs for depression can improve treatment rates and outcomes for depressed primary care patients with comorbid medical illness. The authors discuss the implications of these findings for clinical practice.     

Identifying Depressed Patients With a High Risk of Comorbid Anxiety in Primary Care

BACKGROUND: Depressive and anxiety disorders are highly prevalent in the primary care setting. There is evidence that patients with depression and comorbid anxiety are more severely impaired than patients with depression alone and require aggressive mental health treatment. The goal of this study was to assess the impact of comorbid anxiety in a primary care population of depressed patients. METHOD: 342 subjects diagnosed with a DSM-IV-defined major depressive episode, dysthymia, or both were asked 2 questions about the presence of comorbid anxiety symptoms (history of panic attacks and/or flashbacks). Patient groups included depression only (N = 119), depression and panic attacks (N = 51), depression and flashbacks (N = 97), and depression and both panic attacks and flashbacks (N = 75). Groups were compared on demographics, mental health histories, and health-related quality-of-life variables. Data were gathered from January 1998 to March 1999. RESULTS: Those patients with depression, panic attacks, and flashback symptoms as compared with those with depression alone were more likely to be younger, unmarried, and female. The group with depression, panic attacks, and flashbacks was also more likely to have more depressive symptoms, more impaired health status, worse disability, and a more complicated and persistent history of mental illness. Regression analysis revealed that the greatest impact on disability, presence of depressive symptoms, and mental health outcomes was associated with panic attacks. CONCLUSION: By asking 2 questions about comorbid anxiety symptoms, primary care providers evaluating depressed patients may be able to identify a group of significantly impaired patients at high risk of anxiety disorders who might benefit from collaboration with or referral to a mental health specialist.     

焦虑症共病抑郁症状在门诊患者中的调查研究

目的调查门诊患者中焦虑症的患病率以及共病抑郁症状的发生率。方法在我院精神科门诊、心理咨询门诊以及社区卫生服务中心内科门诊就诊的1106例患者作为研究对象，并做SAS、SDS、HAMA量表评定。结果1106例患者中，符合焦虑症诊断，且HAMA≥14分者共93例，患病率为8.41%。SDS标准分≥50共病抑郁症状的共43例，占46.23%。HAMA分值、SAS分值与SDS分值有显著性正相关。结论门诊中罹患焦虑症的患者焦虑程度越高，共病抑郁的可能性就越大。     

Dysphoria: a major symptom factor in persons with disability or chronic illness.

Depression frequently is diagnosed in persons with chronic illness or following the onset of disability. The overlap of symptoms of many chronic illnesses and disabling conditions with depression may lead to an overestimation of depression in such populations. Some investigators have proposed revised criteria for diagnosing depression in these conditions without an understanding of the contribution of diagnostic criteria in disabling conditions. This study investigated the nature of depressive symptom criteria constellations by individually factor analyzing the Inventory to Diagnose Depression (based on DSM-III diagnostic criteria) in spinal cord injury (n = 134), rheumatoid arthritis (n = 78), student (n = 140), and community (n = 150) groups. A four-factor solution emerged, with the first factor labeled "dysphoria" being represented by symptoms of negative self-evaluations, depressed affect, and suicidal ideation. The results indicate that a core element of the syndrome of depression is dysphoria, which suggests that the contribution of somatic items may be less important to the identification of the depressive syndrome in chronic illness.