Chapter 15

Depression and anxiety disorders are the most common mental illnesses, each affecting in excess of 10-15% of the population at some time in their lives. Both anxiety and depressive disorders are amenable to pharmacological treatments that have been developed since the 1950s. With the discovery of more selective and safer drugs, the use of antidepressants and anxiolytics has moved from the domain of psychiatry to other medical specialties, including primary care. The relative safety of the majority of commonly used antidepressants and anxiolytics notwithstanding, their optimal use requires a clear understanding of their mechanisms of action, pharmacokinetics, potential drug interactions, and the differential diagnosis of psychiatric illnesses.

A confluence of symptoms of depression and anxiety may affect an individual patient; some of the drugs discussed here are effective in treating both disorders, suggesting common underlying mechanisms of pathophysiology and response to pharmacotherapy. In large measure, our current understanding of pathophysiological mechanisms underlying depression and anxiety has been inferred from the mechanisms of action of psychopharmacological compounds (Chapter 14). While depression and anxiety disorders comprise a wide range of symptoms, including changes in mood, behavior, somatic function, and cognition, some progress has been made in developing animal models that respond with some sensitivity and selectivity to antidepressant or anxiolytic drugs (Cryan and Holmes, 2005; Miller et al., 2010). Recent work has focused on identifying endophenotypes associated with psychiatric diseases, with the goals of understanding their underlying pathophysiology and targeting them pharmacologically (Cannon and Keller, 2006). Although animal models are useful for investigating pharmacological mechanisms of action and providing initial evidence of efficacy, the development of antidepressant and anxiolytic drugs depends on clinical trials. However, it is not uncommon for psychopharmacological agents to fail to show efficacy in clinical trials; in large measure this is due to significant placebo effects and the lack of objective and firm end points. In spite of these limitations, the last half century has seen notable advances in the discovery and development of drugs for treating depression and anxiety.

### Symptoms of Depression

Depression, in general, is classified as major depression (i.e., unipolar depression) or bipolar depression (i.e., manic depressive illness); bipolar depression and its treatment are discussed in Chapter 16. Lifetime risk of unipolar depression is ~15%. Females are affected twice as frequently as males (Kessler et al., 1994). Depressive episodes are characterized by depressed or sad mood, pessimistic worry, diminished interest in normal activities, mental slowing and poor concentration, insomnia or increased sleep, significant weight loss or gain due to altered eating and activity patterns, psychomotor agitation or retardation, feelings of guilt and worthlessness, decreased energy and libido, and suicidal ideation, occurring most days for a period of at least 2 weeks. In some cases, the primary complaint of patients involves somatic pain or other physical symptoms and can present a diagnostic challenge for primary care physicians. Depressive symptoms also can occur secondary ...

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