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ANTIDEPRESSANT Antidepressants are a diverse group of drugs that demonstrate a capacity to produce improvement in the symptoms of clinical depression, and they are used to treat the abnormal mood states that characterize depressive illnesses. The word depression is used commonly to describe a state of sadness; but health professionals use the term in a more restricted or defined manner to describe several psychiatric disorders characterized by abnormal moods. One of these is bipolar disorder, in which periods of depression (marked by dejection, lack of energy, inactivity, and sadness) alternate with periods of manic behavior (marked by abnormally high energy levels and increased activity). Another is major depression, which is often a recurring problem characterized by severe and prolonged periods of depression without the manic swing. A third is dysthymia, a chronic mood state characterized by depression and irritability, which was once referred to as depressive neurosis. The signs and symptoms of depressive mood disorders may occur as part of other medical and psychiatric disorders (i.e., following stroke); as a result of endocrine disorders; or as a consequence of excessive drug use. Often these abnormal mood states may not meet established criteria for one of the major psychiatric mood disorders, but they may nevertheless respond to one of the antidepressant drugs.

Antidepressants can also be useful in a number of medical and psychiatric disorders where depression is not the major feature. For example, some categories of antidepressants can be used to treat anxiety and panic disorders, and they are often useful as adjunctive medications for chronic pain. Antidepressant drugs are not generally helpful for short-term depressed moods that are part of everyday life or for the normal period of grief that follows the loss of a loved one.

New categories of antidepressants are being continuously developed and tested. There are now at least five categories in use. These include tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, lithium, nontricyclic antidepressants, and se-rotonin-reuptake inhibitors (SSRIs). The chemical structures of some of these are shown below.

The tricyclic antidepressants, which have been used for many years in the treatment of depression, include such compounds as imipramine (Tofranil), nortriptyline (Aventyl), and desipramine (Norpramin). In addition to being used to treat depression, imipramine is sometimes used to treat alcoholism and cocaine withdrawal. Desipramine is also sometimes used to treat depression associated with cocaine withdrawal. In terms of dosage, most of the tricyclics can be given in a single dose at bedtime. The tricyclics as a group, however, have two major drawbacks. First, the patient must take a specific tricyclic for a period of 2 to 4 weeks before signs of clinical effectiveness occur. Second, the tricyclics have a relatively narrow margin of safety, which means that it is easier for a depressed patient to take an overdose. As a rule, physicians are cautious about prescribing tricyclic antidepressants if the patient appears to be at risk for suicide.

The monoamine oxidase (MAO) inhibitors are generally used as second-line drugs for depressed patients who do not respond to tricyclics, because they require certain dietary restrictions (patients are not allowed liver, aged meats, most cheeses, red wine, soy sauce, etc.) The MAO inhibitors are, however, first-choice drugs for treatment of panic disorder and of depression in the elderly. They include phenelzine sulfate (Nardil), isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate). These antidepressants may be given in either the morning or the evening, depending on their effect on the patient's sleep.

Although lithium (Eskalith, Lithonate) is useful in treating manic states and in preventing depression in bipolar disorders, it is not generally used for other types of depression. Lithium may have serious side effects and may be toxic at high dosages. Exposure to lithium in early pregnancy is associated with an increased frequency of birth defects, and the long-term use of lithium damages kidney function. It also seems to have no significant value in treating cocaine dependence or alcoholism.

The serotonin reuptake inhibitors (SSRIs) are the newest category of antidepressant medications. They have become the most widely used drugs for depression; fluoxetine (Prozac) has been the best-selling antidepressant since the mid-1990s. Other SSRIs include paroxetine (Paxil) and sertraline (Zoloft). A fourth drug, bupropion (Wellbutrin), is not an SSRI but is often grouped with them because it is a newer antidepressant. The SSRIs have several advantages: They can often nip mild depression ''in the bud'' before it develops into a major depressive episode. They can also be used to treat bulimia, obesity, and obsessive-compulsive disorder as well as depression. Since insomnia is a common side effect of SSRIs, they are usually given as a single dose in the morning. The SSRIs also have several disadvantages, including a long response time (patients may need to wait 4 weeks to see any improvement); the same failure rate as the older tricyclics (20-40percent of patients); side effects that include sexual dysfunction; and high cost ($2-3 per tablet).

When a patient does not respond to a specific antidepressant after a trial of 2 to 4 weeks, the physician may prescribe another medication. If the new drug is from the same group as the first antidepressant, the physician can rapidly decrease the dosage of the first drug while increasing the dosage of the second. If, however, the new antidepressant is from a different category, a ''washout time'' must be allowed in order to prevent drug interactions. A washout period of 2 to 3 weeks is necessary when the patient is switched from an MAO inhibitor to a tricyclic; a period of 4 to 5 weeks is necessary when switching from an SSRI to an MAO inhibitor.


American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders, 4th ed. (DSM-IV). Washington, DC. Baldessarini, R. J. (1991). Drugs and the treatment of psychiatric disorders. In: A. G. Gilman et al. (Eds.), Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York: Pergamon. Eisendrath, S. J. (1998). Psychiatric Disorders. InL. M. Tierney et al. (Eds.), Current Medical Diagnosis & Treatment, 37th ed. Stamford, CT: Appleton & Lange.

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