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Definition

Antidepressant drugs are medicines that relieve symptoms of depressive disorders.

Purpose
Depressive disorders may be either unipolar (depression alone) or bipolar (depression alternating with periods of extreme excitation). The formal diagnosis requires a cluster of symptoms, lasting at least two weeks. These symptoms include, but are not limited to mood changes, insomnia or hypersomnia, and diminished interest in daily activities. The symptoms are not caused by any medical condition, drug side effect, or adverse life event. The condition is severe enough to cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Secondary depression, depression caused by unfavorable life events, is normally self limiting, and may be best treated with cognitive/behavioral therapy rather than drugs.

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Description
Antidepressant agents act by increasing the levels of excitatory neurostransmitters. The main types of antidepressant drugs in use today are:

• •

tricyclic antidepressants, such as amitriptyline (Elavil), imipramine (Tofranil), nortriptyline (Pamelor) selective serotonin reuptake inhibitors (SSRIs or serotonin boosters), such as fluoxetine (Prozac), paroxetine

(Paxil), and sertraline (Zoloft) • monoamine oxidase inhibitors (MAO inhibitors), such as phenelzine (Nardil), and tranylcypromine (Parnate)

tetracyclic compounds and atypical antidepressants which do not fall into any of the above categories

Selective serotonin reuptake inhibitors maintain levels of the excitatory neurohormone serotonin in the brain. They do not alter levels of norepinephrine. These have become the drugs of choice for a variety of psychiatric disorders, primarily because of their low incidence of severe side effects as compared with other drugs in this therapeutic class. SSRIs show similar actions and side effect profiles, but may vary in duration of action. Tricyclic compounds, identified by their chemical structure containing three carbon rings, are an older class of antidepressants. Although generally effective, they have a high incidence of anticholinergic effects, notably dry mouth and dry eyes, which can cause discomfort. They also cause cardiac arrythmias. Because tricyclics act on both serotonin and

have some action against monoamine oxidase B. drowsiness. hydrochloride) vomiting Elavil (amitriptyline Constipation. diarrhea.norepinephrine. cramps. nausea. weight gain or loss Nardil (phenelzine sulfate) Dry mouth. Drugs in this class are often available at low prices. they differ in their balance of activity on serotonine and norepinephrine levels. used in treatment ofParkinson's disease) and the herb. John's wort. rash. dizziness. marketed in generic form only) and mirtazepine (Remeron) are similar in chemical structures. idzziness. vomiting Tofranil (imipramine Bleeding sores. hives. They have also been found useful in control of some neurologic pain syndromes. which may be significant when cost is a major factor in treatment. Monoamine oxidase inhibitors (phenelzine [Nardil]. fever. The MAOIs are normally reserved for patients who are resistant to safer drugs. headache. . dizziness. most notably the degree of sedation and the extent of the anticholinergic effects. nausea. headache Effexor (venlafaxine Diarrhea. nausea. headache. drowsiness. flushing. they may have some value in treatment of patients who fail to respond to SSRIs. headache. dopamine. nervousness in therapy because of their high risk of severe adverse effects. seizures Wellbutrin (bupropion Agitation. dry mouth. St. fluid retention. fatigue. gas. Two drugs. and have shown some value as anti-depressants. headache. Although maprotilene (no brand name. Tricyclic antidepressants are similar. fatigue. tremors Norpramin (desipramine Blurred vision.epinephrine. which is responsible for the metabolism of the stimulatory neurohormones norepinephrine. but may vary in severity of side effects. Tetracyclic compounds and atypical antidepressants are chemically distinct from both the major groups and each other. itching. headache. muscle spasms. fever. rash hydrochloride) Zoloft (sertraline) Diarrhea. They act by inhibiting the enzyme monoamine oxidase. headache. hydrochloride) nausea. fatigue. decreased coordination hydrochloride) Travil Asthma. high blood pressure. fatigue. stomach pain Prozac (fluoxetine Bronchitis. vomiting hydrochloride) Pamelor (nortriptyline Diarrhea. constipation. They do not share the same risks as the non-selective MAO inhibitors. rash. fainting. nervousness. blurred vision. decreased coordination hydrochloride) Paxil (paroxetine hydrochloride) Cold symptoms. hair loss. most notably severehypertension. insommia. tranylcypromine [Parnate]) have largely been supplanted Antidepressant Drugs Brand Name (Generic Name) Possible Common Side Effects Include: Desyrel (trazodone Allergic skin reactions. and serotonin. decreased appetite. hydrochloride) fluid retention. eldepryl (Carbex. hallucinations. gas. increased hydrochloride) heartbeat Surmontil (trimipramine maleate) Disorientation. tremors hydrochloride) Sinequan (doxepin Bruising.

Tricyclic antidepressants are in pregnancy categories C or D.All antidepressant agents. Tetracyclics and atypicals. Amoxepine (not marketed by brand. The most common side effect of SSRIs is excitation and insomnia. Significant weight loss has been frequently reported. Although adverse effects may be seen as early as the first dose. all additions to the patient's drug regimen should be reviewed with care. The drugs are excreted in breast milk. Allow a wash-out period of about four weeks before switching from one class of drugs to the other. stroke. specific references should be consulted for more complete information. regardless of their structure. a potentially fatal syndrome whose symptoms include high fever. the effects of antidepressants will continue for a similar length of time after the drugs have been discontinued. Most SSRIs are excreted in breast milk. Consult specific references. such as dry mouth. Precautions Antidepressants have many significant cautions and adverse effects. Although a few are listed here. Excitation has been reported in over 20% of patients. Safety in breast feeding has not been established. altered mental status. SSRIs. irregular pulse or blood pressure. . These adverse effects have not been reported with other tricyclic antidepressants. Similarly. SSRIs should not be administered with MAOIs. chianti wine. including tardive dyskinesias (drug induced involuntary movements) and neuroleptic malignant syndrome. MAOIs are in pregnancy category C. MAOIs have many interactions. but some anecdotal reports of malformations have resulted from animal studies. and patients should be cautioned not to perform tasks requiring alertness until they have evaluated the effects of these drugs. and may progress to congestive heart failure. Recommended dosage Dose varies with the specific drug and patient. significant therapeutic improvement is always delayed. There are no studies of effects on newborns. Because these drugs are individual. SSRIs may cause some sedation. Alterations in heartbeat are also common. Because of the severity of MAOI interactions. Consult specialized references. and there have been anecdotal reports of somnolence in infants whose mothers were taking SSRIs while breastfeeding. Sedation and gastrointestinal disturbances are also common. More common adverse reactions may include low blood pressure and slowing of heartbeat. and changes in heart rate. dry eyes. typically three to five weeks. displays some of the more serious effects of the neuroleptics. some severe. These include aged cheese. specific references should be consulted for more complete information. Interactions The antidepressants have many drug interactions. and many others. there are no group patterns of adverse reactions. SSRIs are pregnancy category C drugs. have a slow onset of action. however the best known are those with foods containing the amino acid tyramine. but most commonly in patients who are already underweight. Patients and providers should review the MAOI diet restrictions before using or prescribing these drugs. and sudden death. The greatest risk associated with these drugs is a hypertensive crisis which may be fatal and most often occurs when the drugs are taken with interacting foods or drugs. Monoamine oxidase inhibitors. generic available). although there have been no formal studies of the drugs on fetal development. The most common adverse effects of tricyclic antidepressants are sedation and the anticholinergic effects. and difficult urination. Tricyclic antidepressants. Although a few are listed here. although a tricyclic antidepressant rather than a neuroleptic (major tranquilizer). Allow five weeks if switching from fluoxetine (Prozac) to an MAOI. and insomnia in 33%.

Pregnancy category—A system of classifying drugs according to their established risks for use during pregnancy. PharmD KEY TERMS Cognitive behavioral therapy—A type of psychotherapy in which people learn to recognize and change negative and selfdefeating patterns of thinking and behavior. or with anti-epileptic agents such as phenytoin (Dilantin) or carbamazepine (Tegretol). but not in well-controlled human studies. Samuel Uretsky. SSRIs interact with a number of other drugs which act on the central nervous system. Specifically avoid other drugs with anticholinergic effects. or adverse fetal effects in animal studies. or adverse effects in animals. Tricyclics should not be taken with the antibiotics grepafloxacin and sprafloxacin. Tricyclic compounds should not be taken with the gastric acid inhibitor cimetidine(Tagamet). Category D: Evidence of fetal risk.Tricyclic compounds have many interactions. since this increases the blood levels of the tricyclic compound." Health Facts 20 (February 1995): 189. Other acid inhibiting drugs do not share this interaction. Depression—A mental condition in which people feel extremely sad and lose interest in life. Use care in combining these drugs with major or minor tranquilizers. . but no human studies. and specialized references should be consulted. Category B: Animal studies indicate no fetal risk. but no available human data. Category C: No adequate human or animal studies. Category A: Controlled human studies have demonstrated no fetal risk. since the combination may cause serious heart arrythmias. People with depression may also have sleep problems and loss of appetite and may have trouble concentrating and carrying out everyday activities. PERIODICALS "Treatment of Depression: Drugs Alone Are Not Enough.