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Tricyclic Antidepressants (TCAs)

Information and Side Effects of Tricyclic Antidepressants


Updated January 26, 2009

Tricyclic antidepressants (TCAs) are named after the drugs’ “three ringed” molecular structure. Prior to the introduction of (SSRIs) in the late 1980s, TCAs were the medication of choice for the treatment of major depressive disorder, panic disorder and other anxiety disorders. TCAs are also used to treat certain pain syndromes and nocturnal enuresis (bedwetting).

How TCAs Work

It is believed that the brain contains several hundred different types of chemical messengers (neurotransmitters) that act as communication agents between different brain cells. TCAs function to inhibit the reuptake of two chemical messengers, norepinephrine and serotonin, causing increased levels of both in the brain.

Serotonin plays a role in modulating a variety of body functions and feelings. Low serotonin levels have been linked to depression and anxiety. Norepinephrine is believed to be associated with the fight or flight stress response. It contributes to feelings of alertness, fear, anxiety and panic.

Common Side Effects of TCAs

  • dry mouth
  • constipation
  • increased appetite
  • weight gain
  • drowsiness
  • difficult urination
  • blurred vision
  • nausea
  • sensitivity to sunlight

Some of these side effects will diminish after your body adjusts to the medication. If they don’t and are bothersome, your doctor may try a different medication. Although TCAs function by a similar mode of action, there are some differences in their effectiveness and relative side-effect profiles. Certain side effects with one TCA may not be as problematic with another.

Precautions and Contraindications

Before beginning TCA therapy, tell your doctor if you have any of the following conditions:

  • narrow-angle glaucoma
  • an enlarged prostate
  • heart disease
  • diabetes
  • seizure disorder

TCAs should never be taken with a class of antidepressants called monoamine oxidase inhibitors (MAOIs). It is recommended that TCA therapy be avoided for at least two weeks before or after using an MAOI.

TCAs should be taken exactly as prescribed by your healthcare provider. Never take more of a TCA than has been prescribed. The therapeutic dose of a TCA is close to its toxic dose. In other words, a small increase above the prescribed dose may result in overdose. A suspected overdose involving a TCA requires immediate medical intervention as the condition can be fatal.

Serotonin Syndrome

Dangerously high levels of serotonin in the brain can cause a potentially life-threatening condition called serotonin syndrome. This rare condition is usually the result of an interaction of two or more drugs that affect brain serotonin levels. Even some over-the-counter supplements, such as St. John’s Wort, can result in serotonin syndrome if mixed with TCAs.

Signs and symptoms of serotonin syndrome include:

  • confusion
  • restlessness
  • hallucinations
  • extreme agitation
  • fluctuations in blood pressure
  • heart palpitations
  • nausea
  • fever
  • seizures
  • coma

To avoid possible drug interactions, make sure all of your treating doctors know you are taking a TCA. Before taking any over-the-counter medications or dietary supplements while you are on a TCA, check with your doctor.

TCAs and Pregnancy

The research on pregnancy and TCA therapy is limited. There are some reports that newborns may experience difficulties, including heart and breathing problems, when exposed to TCAs during late pregnancy. If you are nursing or are pregnant, it is best to discuss the risks and benefits of TCA therapy with your doctor.

TCA Discontinuation Syndrome

Some people have reported withdrawal-like symptoms when decreasing or stopping TCA therapy. It is believed that these symptoms are a result of the brain trying to stabilize serotonin and norepinephrine levels after an abrupt change.

Symptoms that may occur during discontinuation of TCA therapy include:

  • nausea
  • headache
  • muscle aches
  • Dizziness
  • electric shock-like sensations in the neck and head

While all of these symptoms are not believed to be dangerous, they can be quite disconcerting. When discontinuing a TCA, your doctor may give you a gradual reduction schedule to avoid these withdrawal-like symptoms.

TCAs and Suicide

The association of increased suicidal thoughts, especially among adolescents, with SSRI treatment has been a center of attention and controversy in recent years. In response to the concerns suggested in case studies and some research, the U.S. Food and Drug Administration (FDA) issued a statement in 2007. The FDA proposed that makers of all antidepressant medications indicate a warning on their products about a possible increased risk of suicidal thinking and behavior in young adults, ages 18 to 24, during initial treatment.

So far, researchers have not found a definitive answer about the antidepressant-suicide connection. For the vast majority of people, antidepressants decrease depression and alleviate the helplessness and hopelessness that consumes their daily existence. But, for a very small percentage of people taking antidepressants, this may not be the case. If you are concerned about this issue, be open with your doctor and don’t be afraid to ask questions.


Antidepressant Use in Children, Adolescents, and Adults. Revisions to Product Labeling. U.S. Food and Drug Administration. May 2, 2007.

Prator, Bettina C. Serotonin Syndrome. Journal of Neuroscience Nursing. 2006. 38(2):102-105. 15 Oct 2008.

United States Department of Veterans Affairs. Tricyclic Antidepressants. 19 Oct 2008.

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