Overview of Tricyclic Antidepressants

Older-generation drugs still have their place in treatment

Doctor explaining prescription medication to patient in clinic

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Tricyclic antidepressants (TCAs) are drugs used to treat depression, bipolar disorder, and other conditions such as chronic pain and insomnia. While newer classes of antidepressant have far fewer side effects, TCAs still have their place in the treatment of these and other disorders. First introduced in the 1950s, tricyclic antidepressants are so-named because their molecular structure is composed of three rings of atoms.

How Tricyclic Antidepressants Work

Broadly speaking, depression is caused by a chemical imbalance in the brain which results in abnormal communications between nerve cells (neurons). The chemicals that deliver these messages are called neurotransmitters.

These chemical messages are relayed from one neuron to the next and, depending on the type of neurotransmitter involved, can influence how you feel and react.

Tricyclic antidepressants work by preventing the reabsorption of neurotransmitters called serotonin and norepinephrine. The body needs both of these to function normally. If there is too much of either, you may end up experiencing anxiety. If there is not enough, depression may ensue.

Because TCAs prevent the routine reabsorption (reuptake) of these neurotransmitters, there will be more freely circulating in the synaptic cleft between neurons in the brain. If you have depression, the restoration of the serotonin and norepinephrine levels can lead to an improvement in your symptoms.

Conditions Treated

Tricyclic antidepressants are used primarily to treat mood disorders but also have their place in the treatment of anxiety disorders, personality disorders, and neurological disorders. They are often used when other drugs are unable to provide relief.

Mood disorders often treated with TCAs include:

Anxiety disorders sometimes treated with TCAs include:

Neurological disorders sometimes treated with tricyclic TCAs include:

TCAs may also be used to treat insomnia, irritable bowel syndrome (IBS), interstitial cystitis, nocturnal enuresis (bedwetting), narcolepsy, and chronic hiccups.

Approved Medications

With tricyclic antidepressants, like other antidepressants, it will usually take between six to eight weeks before you feel any substantial improvement in your depression symptoms. Some of the more commonly prescribed TCAs include:

  • Anafranil (clomipramine)
  • Ascendin (amoxapine)
  • Elavil (amitriptyline)
  • Norpramin (desipramine)
  • Pamelor (nortriptyline)
  • Sinequan (doxepin)
  • Surmontil (trimipramine)
  • Tofranil (imipramine)
  • Vivactil (protriptyline)

Common Side Effects

While different TCAs have slightly different mechanisms of action, they share similar side effects. Many of these are associated with the effect the drugs have on the smooth muscles of the internal organs. Common side effects include:

  • Anxiety
  • Blurred vision
  • Constipation
  • Dizziness
  • Drowsiness
  • Increased appetite
  • Muscle twitches
  • Nausea and vomiting
  • Rapid or irregular heart rate
  • Sexual dysfunction
  • Sweating
  • Weakness
  • Weight gain

These side effects may be reduced if treatment is started with lower dosages and then gradually increased. While not strictly addictive per se, the long-term use of TCAs may lead to drug dependence.

TCAs are also a significant cause of fatal drug overdoses in the United States. Initial symptoms may include dry mouth, blurred vision, urinary retention, constipation, dizziness, vomiting, and hallucinations. If left untreated, an overdose may result in delirium, seizures, coma, cardiac arrest, and death.

Drug Interactions

Some of the side effects of tricyclic antidepressants may be intensified if taken with other drugs. In other cases, it can affect the bioavailability (concentration) of the drug in the bloodstream.

As such, you should always advise your doctor about any substances you may be taking, including over-the-counter medications, herbal remedies, and recreational drugs. Certain drugs are contraindicated for use with tricyclic antidepressants, including:

  • Alcohol blocks the action of TCAs and should be avoided.
  • Anticholinergic drugs used to treat urinary incontinence and COPD can cause intestinal paralysis if co-administered with a TCA.
  • Clonidine, used to treat hypertension, can trigger a dangerous rise in blood pressure if used with a TCA.
  • Epinephrine used to treat severe allergic reactions can also trigger severe high blood pressure if used with a TCA.
  • Monoamine oxidase (MAO) inhibitors, also used as antidepressants, can cause high fever, convulsions, and even death is coadministered with a TCA.
  • Tagamet (cimetidine), used to reduce stomach acid, may increase the concentration of the TCA in your blood, further intensifying the drug side effects.

A Word From Verywell

Tricyclic antidepressants can be effective in treating depression but may not work as well in some people as others. In some cases, the drug side effects may become intolerable and interfere with your very quality of life. If you are suffering serious side effects, call your doctor immediately but do not stop treatment until your doctor tells you to.

Stopping abruptly can cause symptoms of withdrawal, including nausea, fever, chills, headache, dizziness, lethargy, and vomiting. Your doctor may be able to lower your dosage to where treatment is tolerable. If not, he or she would need to gradually taper the dose until you are able to safely stop.

5 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Massachusetts General Hospital. Somber Questions.

  2. Anxiety and Depression Association of America. Medication.

  3. National Center for Biotechnology Information. Depression: How effective are antidepressants?

  4. Hawton K, Bergen H, Simkin S, et al. Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose. Br J Psychiatry. 2010;196(5):354-8. doi:10.1192%2Fbjp.bp.109.070219

  5. U.S. Food and Drug Administration. Pamelor Label.

Additional Reading

By Marcia Purse
Marcia Purse is a mental health writer and bipolar disorder advocate who brings strong research skills and personal experiences to her writing.