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Key Clinical Questions Depression

  • image What are the signs and symptoms of a major depressive episode (MDE)?

  • image What is the pathophysiology of major depression?

  • image What medications, intoxicants, and diseases cause depressed mood?

  • image What is adjustment disorder?

  • image What is the appropriate diagnostic workup for a patient with depressive symptoms?

  • image What is the treatment for major depressive disorder (MDD)?

  • image What are the complications of antidepressant use?

Bipolar Disorder
  • image What are the signs and symptoms of bipolar disorder?

  • image What medical conditions and substances can induce mania?

  • image What is the appropriate diagnostic workup for a patient with mania?

  • image How is bipolar disorder treated?

Anxiety Disorders
  • image What are the signs and symptoms of anxiety?

  • image What are the common anxiety disorders?

  • image How does generalized anxiety disorder (GAD) differ from major depression?

  • image What medical conditions present with symptoms of anxiety?

  • image What studies should be ordered for the acutely anxious patient?

  • image What is the treatment for anxiety?


Major depressive disorder (MDD) is widespread and devastating, with lifetime prevalence greater than 17% in the general population. Total costs exceed $44 billion annually, including hospitalization, medications, and loss of productivity. In medically ill patients, mood disorders are even more common; 6-month prevalence increases from 5.8% to 9.4% with at least one chronic medical condition. Despite this, many physicians fail to address depressive symptoms, believing them to be appropriate in illness (“I would be depressed too, if I were that sick”). This misconception leads to poor outcomes, as physical recovery is impeded by affective disorders.

CASE 223-1

A 66-year-old man with a history of type-2 diabetes, hypertension, and tobacco use was admitted for non-ST elevation myocardial infarction (MI) and cardiac catheterization with stent placement. During morning rounds, his care team noted that the patient ate only about 10% of his breakfast and appeared to have a blunted affect. He had a history of multiple episodes of depressed mood, insomnia, and anhedonia over the years. The patient reported feeling “worthless” and sometimes wishing that he had “just gone ahead and died.” Though initially reluctant because of worries about dependence, Mr G agreed to try an antidepressant, sertraline. At his 6-week posthospitalization appointment he is free of mood symptoms, engaged in cardiac rehabilitation and feels hopeful about the future.


The primary etiology of major depression remains obscure. ­Dysregulation of central nervous system (CNS) monoamine neurotransmitters (including norepinephrine, serotonin, and dopamine) occurs in MDD. Newer theories focus on broader neuroregulatory circuits involving cholingeric activation, GABA hypoactivity, and chronically elevated hypothalamic-pituitary-adrenal activity. Immune system abnormalities and increased inflammation likely play a role, particularly in medically ill individuals.


Major depressive disorder

Major depressive disorder is defined by the occurrence of one or more major depressive episodes (see Table 223-1). Though many patients will readily admit to feeling “sad” or “down,” ...

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