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Major depression is one of the most common forms of mental illness in the United States with as many as 6% of the population depressed at any given moment (point prevalence), and an estimated 10% of people becoming depressed during their lifetime (lifetime prevalence). The symptoms of depression can be both psychologic and physiologic, and are often subtle and unrecognized by patients and health-care professionals. Symptoms may include intense feelings of sadness and despair, sleep disturbances (too much or too little), anorexia, fatigue, somatic complaints, and suicidal thoughts.

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Depression is a heterogeneous disorder that has been classified as (1) “reactive” or “secondary” depression (most common), occurring in response to stimuli such as grief or illness; (2) “endogenous” depression or major depressive disorder, a genetically determined biochemical disorder of depressed mood without any obvious medical or situational causes, manifested by an inability to experience ordinary pleasure or to cope with ordinary life events; and (3) depression associated with bipolar affective (manic-depressive) disorder.

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Physical therapists may encounter patients taking antidepressant medications under a number of circumstances. Many patients who have experienced life-changing disabilities become depressed and may require medication for a limited time to control their depression. Other patients may have a history of chronic depression not related to their therapy diagnosis and require long-term treatment. Drugs used in treating depressive disorders are highly effective in some patients but only modestly, or not at all, effective in others. No patients are cured. The major subclasses of antidepressant drugs are outlined in Figure 19–1.

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Figure 19–1.
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Major subclasses of antidepressants.

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The amine hypothesis of mood postulates that brain amines, particularly norepinephrine (NE) and (serotonin, 5-HT), are neurotransmitters in pathways that function in the expression of mood. According to the hypothesis, a functional decrease in the activity of such amines is thought to result in depression; a functional increase in activity results in mood elevation. The amine hypothesis is largely based on studies showing that drugs (such as reserpine) that deplete central amines cause depression, and that most drugs capable of alleviating the symptoms of a major depressive disorder enhance the actions of the neurotransmitters 5-HT and NE in central synapses. Difficulties with this hypothesis include the facts that (1) postmortem studies do not reveal any decreases in the brain levels of NE or 5-HT in untreated patients suffering from endogenous depression; (2) although antidepressant drugs may cause biochemical changes in brain amine activity within hours, weeks may be required for them to achieve clinical effects; (3) with chronic use, most antidepressants ultimately cause a down-regulation of amine receptors; and (4) at least one effective antidepressant, bupropion, has minimal effects on brain NE or 5-HT.

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While the amine hypothesis is undoubtedly too simplistic, it has provided the major experimental models for the discovery of new antidepressant drugs. ...

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