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Antidepressant Drugs

Definition, Purpose, Description, Recommended dosage, Precautions, Interactions

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.

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 norepinephrine, they may have some value in treatment of patients who fail to respond to SSRIs. Drugs in this class are often available at low prices, which may be significant when cost is a major factor in treatment. They have also been found useful in control of some neurologic pain syndromes.

Tricyclic antidepressants are similar, but may vary in severity of side effects, most notably the degree of sedation and the extent of the anticholinergic effects.

Tetracyclic compounds and atypical antidepressants are chemically distinct from both the major groups and each other. Although maprotilene (no brand name, marketed in generic form only) and mirtazepine (Remeron) are similar in chemical structures, they differ in their balance of activity on serotonine and norepinephrine levels.

Monoamine oxidase inhibitors (phenelzine [Nardil], tranylcypromine [Parnate]) have largely been supplanted

Antidepressant Drugs

Antidepressant Drugs
Brand Name (Generic Name) Possible Common Side Effects Include:
Desyrel (trazodone hydrochloride) Allergic skin reactions, blurred vision, decreased appetite, fluid retention, headache
Effexor (venlafaxine hydrochloride) Diarrhea, dizziness, gas, headache, insommia, rash, vomiting
Elavil (amitriptyline hydrochloride) Constipation, idzziness, high blood pressure, fever, nausea, rash, weight gain or loss
Nardil (phenelzine sulfate) Dry mouth, fatigue, headache, muscle spasms, tremors
Norpramin (desipramine hydrochloride) Blurred vision, cramps, hallucinations, hair loss, vomiting
Pamelor (nortriptyline hydrochloride) Diarrhea, fatigue, headache, decreased coordination
Paxil (paroxetine hydrochloride) Cold symptoms, drowsiness, nervousness, stomach pain
Prozac (fluoxetine hydrochloride) Bronchitis, drowsiness, fatigue, nausea, tremors
Sinequan (doxepin hydrochloride) Bruising, constipation, fluid retention, itching, increased heartbeat
Surmontil (trimipramine maleate) Disorientation, flushing, headache, nausea, vomiting
Tofranil (imipramine hydrochloride) Bleeding sores, fever, hives, decreased coordination
Travil Asthma, diarrhea, dizziness, fatigue, seizures
Wellbutrin (bupropion hydrochloride) Agitation, dry mouth, headache, nausea, rash
Zoloft (sertraline) Diarrhea, fainting, gas, headache, nervousness

in therapy because of their high risk of severe adverse effects, most notably severe hypertension. They act by inhibiting the enzyme monoamine oxidase, which is responsible for the metabolism of the stimulatory neurohormones norepinephrine, epinephrine, dopamine, and serotonin. The MAOIs are normally reserved for patients who are resistant to safer drugs. Two drugs, eldepryl (Carbex, used in treatment of Parkinson's disease) and the herb, St. John's wort, have some action against monoamine oxidase B, and have shown some value as anti-depressants. They do not share the same risks as the non-selective MAO inhibitors.

All antidepressant agents, regardless of their structure, have a slow onset of action, typically three to five weeks. Although adverse effects may be seen as early as the first dose, significant therapeutic improvement is always delayed. Similarly, the effects of antidepressants will continue for a similar length of time after the drugs have been discontinued.

Recommended dosage

Dose varies with the specific drug and patient. Consult specialized references.

Precautions

Antidepressants have many significant cautions and adverse effects. Although a few are listed here, specific references should be consulted for more complete information.

SSRIs. The most common side effect of SSRIs is excitation and insomnia. Excitation has been reported in over 20% of patients, and insomnia in 33%. Significant weight loss has been frequently reported, but most commonly in patients who are already underweight. SSRIs may cause some sedation, and patients should be cautioned not to perform tasks requiring alertness until they have evaluated the effects of these drugs. SSRIs are pregnancy category C drugs. Most SSRIs are excreted in breast milk, and there have been anecdotal reports of somnolence in infants whose mothers were taking SSRIs while breastfeeding.

Tricyclic antidepressants. Amoxepine (not marketed by brand, generic available), although a tricyclic antidepressant rather than a neuroleptic (major tranquilizer), displays some of the more serious effects of the neuroleptics, including tardive dyskinesias (drug induced involuntary movements) and neuroleptic malignant syndrome, a potentially fatal syndrome whose symptoms include high fever, altered mental status, irregular pulse or blood pressure, and changes in heart rate. These adverse effects have not been reported with other tricyclic antidepressants.

The most common adverse effects of tricyclic antidepressants are sedation and the anticholinergic effects, such as dry mouth, dry eyes, and difficult urination. Alterations in heartbeat are also common, and may progress to congestive heart failure, stroke, and sudden death.

Tricyclic antidepressants are in pregnancy categories C or D, although there have been no formal studies of the drugs on fetal development. There are no studies of effects on newborns, but some anecdotal reports of malformations have resulted from animal studies. The drugs are excreted in breast milk.

Monoamine oxidase inhibitors. 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. More common adverse reactions may include low blood pressure and slowing of heartbeat. Sedation and gastrointestinal disturbances are also common. MAOIs are in pregnancy category C. Safety in breast feeding has not been established.

Tetracyclics and atypicals. Because these drugs are individual, there are no group patterns of adverse reactions. Consult specific references.

Interactions

The antidepressants have many drug interactions, some severe. Although a few are listed here, specific references should be consulted for more complete information.

SSRIs should not be administered with MAOIs. Allow a wash-out period of about four weeks before switching from one class of drugs to the other. Allow five weeks if switching from fluoxetine (Prozac) to an MAOI.

MAOIs have many interactions; however the best known are those with foods containing the amino acid tyramine. These include aged cheese, chianti wine, and many others. Patients and providers should review the MAOI diet restrictions before using or prescribing these drugs. Because of the severity of MAOI interactions, all additions to the patient's drug regimen should be reviewed with care.

Tricyclic compounds have many interactions, and specialized references should be consulted. Specifically avoid other drugs with anticholinergic effects. Tricyclics should not be taken with the antibiotics grepafloxacin and sprafloxacin, since the combination may cause serious heart arrythmias.

Tricyclic compounds should not be taken with the gastric acid inhibitor cimetidine (Tagamet), since this increases the blood levels of the tricyclic compound. Other acid inhibiting drugs do not share this interaction.

SSRIs interact with a number of other drugs which act on the central nervous system. Use care in combining these drugs with major or minor tranquilizers, or with anti-epileptic agents such as phenytoin (Dilantin) or carbamazepine (Tegretol).

Resources

PERIODICALS

"Treatment of Depression: Drugs Alone Are Not Enough." Health Facts 20 (February 1995): 189.

Samuel Uretsky, PharmD

KEY TERMS


Cognitive behavioral therapy—A type of psychotherapy in which people learn to recognize and change negative and self-defeating patterns of thinking and behavior.

Depression—A mental condition in which people feel extremely sad and lose interest in life. People with depression may also have sleep problems and loss of appetite and may have trouble concentrating and carrying out everyday activities.

Pregnancy category—A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk,

Additional topics

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