Treatment of Mood Disorders in the Medically Ill Patient


Greg L. Clary, M.D.
K. Ranga Rama Krishnan, M.D.

The incidence of comorbid mood disorders and general medical illness has been shown to have a tremendous impact on health and the health care system. Studies on depression alone have estimated annual costs in 1990 dollars at $43.7 billion. Many studies have shown increased length of hospitalization and increased cost when both psychiatric and medical illness is present. Among general medical inpatients, the prevalence of a psychiatric disorder varies from 23% to 39%, depending on gender and age, and depressive symptoms are the second most commonly reported symptoms in primary care practice. While a major problem with recognition and treatment of depression in the primary care setting has been recognized, the studies that have garnered the greatest interest are those regarding increased morbidity and mortality associated with comorbid anxiety and depression in medical illness. The question then arises as to the influence, either from a biochemical or a neurochemical perspective, that depression exerts on the progression of the medical illness. If, as many postulate, the biochemical disturbances that occur with many medical illnesses lead to an increased prevalence of depression, are there particular psychotherapeutic and/or psychopharmacological interventions that might benefit both disease states? Approximately two-thirds of depressed patients evaluated in the outpatient setting respond to medications, but the specific therapeutic recommendations for treatment of depressed patients with medical illness are still lacking in clinical research support. Much of this research is being directed with the hope that treatment of the psychiatric disorder will result in mood improvement and a reduction in morbidity and mortality. Our goals in this chapter are to address much of the current knowledge of specific therapeutic modalities for the treatment of mood disorders in patients with general medical conditions and to particularly focus on those treatments that have provided benefit for improvement of the mood disorder and also positively affect the prognosis of the medical illness.


Prevalence of Mood Disorders in Medically Ill Patients
The most common diagnosis in terms of mood disorders in medically ill patients is major depression. Other diagnoses commonly found include depressive symptomatology secondary to a general medical condition, substance-induced mood disorder, adjustment disorder with depressed mood or mixed emotional features, major depression, dysthymic disorder, and depression not otherwise specified. Bipolar disorder is much less common than those previously mentioned. As stated above, mood disorders in patients with medical illness are seen in higher prevalence rates than the rates found in the general population. The rates of depression vary: in renal failure, 6.5%-20%; diabetes mellitus, 10%-20%; cerebral vascular disease, 20%-50%; hyperthyroidism, 10%-30%; AIDS/HIV, 20%-35%; emphysema, 20%-40%; and coronary artery disease, 30%-60%. The mechanism that causes this increased rate is poorly understood. Much has been written on the psychosocial stressors and socioeconomic status that places many of these patients at increased risk for the onset of a depressive episode. Ruberman (1992) reported a four- to fivefold increase in recurrent cardiovascular events post-myocardial infarction (MI) in patients with poor social support systems, and Williams (1998) observed a stepwise increase in mortality from coronary heart disease with decreasing income levels.

Much attention has also been directed toward the pathophysiological influence of psychoneuroendocrinology on depression in medically well as well as medically ill patients. This includes attenuation of serotonin, the noradrenergic system, and adrenocorticotropin hormone secretion; impairments of cortisol secretion; and alteration of platelet aggregation and reactivity. Dysregulation of the autonomic nervous system and of the hypothalamic-pituitary-adrenal (HPA) axis has been found in medically well patients with depressive disorder. The evidence for this includes elevated plasma and urinary catecholamines and their metabolites, elevated plasma and urinary cortisol, elevated resting heart rate, and decreased heart rate variability. Extrapolating from this information, one could conceive that, if depression led to dysregulation of autonomic tone, this malfunction in the cardiac patient with depression could easily lead to the appearance of arrhythmias and increased cardiac death, as suggested by Musselman et al. (1998). This is only preliminary research evidence, but clearly, if we understood these modifying biochemical processes, then selection of a particular pharmacological agent could be made with scientific confidence.

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Revision date: June 18, 2011
Last revised: by Janet A. Staessen, MD, PhD