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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Tricyclics are a class of antidepressant medications that are sometimes used in the treatment and managment of depression. They affect neurotransmitter pathways throughout the body, including serotonin and norepinephrine.

Tricyclic antidepressants (TCAs) are 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 treating 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

Chemicals that deliver messages in the brain 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. Tricyclic antidepressants can help balance the levels of these neurotransmitters.

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 may lead to an improvement in your symptoms.

Tricyclics vs. SSRIS

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed type of antidepressant. While individual effects vary, SSRIs are generally well-tolerated and effective. SSRIs also produce fewer side effects than tricyclics.

While both antidepressants impact serotonin, tricyclics are less selective than SSRIs. They act on receptors throughout the body, including norepinephrine receptors, which means they affect more body systems and have a greater risk for side effects and overdose

SSRIs also tend to have a lower risk of toxicity and overdose, although they can also cause problems if taken in large amounts or combined with other medications that affect serotonin levels.

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.

Because they tend to have more side effects than newer antidepressants, 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.

When Are Tricyclics Prescribed?

Because newer-generation antidepressants have fewer side effects and a lower risk of overdose, tricyclics are prescribed less frequently than they were in the past. However, they are still utilized in some cases, particularly for people who have not found sufficient symptom relief from other antidepressants.

Tricyclics might be prescribed if:

  • Other antidepressants have led to side effects
  • The individual has a condition such as headaches, migraines, or neuropathic pain
  • The individual is experiencing co-occurring depression and insomnia
  • The individual has depression and another co-occurring condition such as PTSD, OCD, or panic disorder

Examples of Tricyclic Antidepressants

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.

Tricyclic Overdose

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.

Interactions and Precautions

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.

Some tricyclic antidepressants can harm your baby if you take them during pregnancy or while breastfeeding, so talk to your doctor if you are pregnant or may become pregnant.

Tricyclics may also increase the risk for anticholinergic effects, cardiac problems, and postural hypotension in older adults. Postural hypotension can lead to falls, increasing a person's risk of experiencing fractures and other injuries.

Serotonin Syndrome

Combining tricyclics with other medications that affect serotonin levels can also lead to a condition known as serotonin syndrome. This potentially dangerous condition occurs when serotonin levels in the body become too high, causing symptoms such as:

  • Anxiety
  • Agitation
  • Changes in blood pressure
  • Confusion
  • Fever
  • Rapid heart rate
  • Tremors

Medications contributing to serotonin syndrome include other antidepressants such as SSRIs and herbal supplements such as St. John's wort.

Tricyclic Withdrawal

Stopping tricyclics or changing the dose can lead to symptoms of withdrawal. Common withdrawal symptoms include nausea, fever, chills, headache, dizziness, lethargy, and vomiting.

To minimize tricyclic withdrawal effects, your doctor may advise gradually lowering your dose over a period of several weeks.

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.

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.