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Tricyclic Antidepressants (TCAs)

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What are tricyclic antidepressants, and how do they work?

Tricyclic antidepressants (TCAs) are a class of antidepressant medications that share a similar chemical structure and biological effects. Scientists believe that patients with depression may have an imbalance in neurotransmitters, chemicals that nerves make and use to communicate with other nerves. Tricyclic antidepressants increase levels of norepinephrine and serotonin, two neurotransmitters, and block the action of acetylcholine, another neurotransmitter. Scientists believe that by restoring the balance in these neurotransmitters in the brain that tricyclic antidepressants alleviate depression. In addition to relieving depression, tricyclic antidepressants also cause sedation and somewhat block effects of histamine.

For what conditions are tricyclic antidepressants used?

Tricyclic antidepressants are approved by the Food and Drug Administration (FDA) for treating several types of depression, obsessive compulsive disorder, and bedwetting.

In addition, they are used for several off-label (non-FDA approved) uses such as:

Are there differences among tricyclic antidepressants?

Tricyclic antidepressants differ in their relative effects on serotonin, norepinephrine, and acetylcholine. The differences are reflected in how the tricyclic antidepressants are used and, most importantly, their propensity to cause certain side effects. For instance, amitriptyline (Elavil) causes more sedation, dry mouth, and constipation than other tricyclic antidepressants.

What are the side effects of tricyclic antidepressants?

Tricyclic antidepressants may cause:

Tricyclic antidepressants should be used cautiously in patients with seizures since they can increase the risk of seizures.

Tricyclic antidepressants may worsen urinary retention (difficulty urinating) and narrow angle glaucoma. Abnormal heart rhythms and sexual dysfunction have also been associated with tricyclic antidepressants.

If tricyclic antidepressants are discontinued abruptly, withdrawal symptoms (for example, dizziness, headache, nausea, and restlessness) may occur. Withdrawal symptoms may occur when even a few doses are missed. Therefore, the dose of antidepressant should be reduced gradually when therapy is discontinued.

Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of any antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be closely observed for clinical worsening, suicidal thinking or behavior, and unusual changes in behavior.

With which drugs do tricyclic antidepressants interact?

Tricyclic antidepressants should not be used with monoamine oxidase inhibiting drugs [for example, tranylcypromine (Parnate)]. High fever, convulsions, and even death can occur from such combinations.

Epinephrine (Primatene, Adrenalin, Ana-Kit, EpiPen, Marcaine) should not be used with tricyclic antidepressants, since together they can cause severe high blood pressure.

Alcohol blocks the antidepressant action of tricyclic antidepressants but increases its sedative effect.

Cimetidine (Tagamet) can increase blood levels and side effects of tricyclic antidepressants.

Combining tricyclic antidepressants with drugs that block acetylcholine can stop bowel movements and paralyze the intestine (paralytic ileus). Dangerous elevations in blood pressure may occur if TCA are combined with clonidine (Catapres, Catapres-TTS).

What are the available tricyclic antidepressants in the U.S.?

The following are approved TCAs in the U.S.:

Reviewed by:
Marina Katz, MD
American Board of Psychiatry & Neurology

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