Table of ContentsView AllTable of ContentsHow Tricyclics WorkTricyclics vs. SSRISConditions TreatedExamples of Tricyclic AntidepressantsCommon Side EffectsInteractions and PrecautionsTricyclic Withdrawal

Table of ContentsView All

View All

Table of Contents

How Tricyclics Work

Tricyclics vs. SSRIS

Conditions Treated

Examples of Tricyclic Antidepressants

Common Side Effects

Interactions and Precautions

Tricyclic Withdrawal

Close

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 calledneurotransmitters. 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.

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 yoursymptoms.

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 andoverdose.

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.

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:

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:

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:

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 OverdoseTCAs 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.

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.

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:

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 asserotonin syndrome. This potentially dangerous condition occurs when serotonin levels in the body become too high, causing symptoms such as:

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

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.

Long-Term Effects of Antidepressants

5 SourcesVerywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Massachusetts General Hospital.Somber Questions.Anxiety and Depression Association of America.Medication.National Center for Biotechnology Information.Depression: How effective are antidepressants?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.109.070219U.S. Food and Drug Administration.Pamelor Label.Additional ReadingAarts, N.: Noordam, R.; Hofman, A.; Tiemeier, J.; Stricker, B.; and L. Visser.Self-Reported Indications for Antidepressant Use in a Population-Based Cohort of Middle-Aged and Elderly.Int J Pharmacol. 2016;38(5):1311-7. DOI: 10.1007/s11096-016-0371-9.Caldwell, P.; Sureshkumar, P.; and W. Wong.Tricyclic and Related Drugs for Nocturnal Enuresis in Children.Cochrane Database Syst Rev.2016;20(1): CD002117. DOI: 10.1002/14651858.CD002117.pub2.Gillman, P.Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.Br J Pharmacol.2007;151(6):737-48. DOI: 10.1038/sj.bjp.0707253.Jobski, K., Schmidt, N., Kolkhorst, B., Krappweis, J., Schink, T., and E. Garbe.Characteristics and Drug Use Patterns of Older Antidepressant Initiators in Germany.Eur J Pharmacol. 2017:73(1):105-13. DOI: doi.org/10.1007/s00228-016-2145-7.

5 Sources

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Massachusetts General Hospital.Somber Questions.Anxiety and Depression Association of America.Medication.National Center for Biotechnology Information.Depression: How effective are antidepressants?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.109.070219U.S. Food and Drug Administration.Pamelor Label.Additional ReadingAarts, N.: Noordam, R.; Hofman, A.; Tiemeier, J.; Stricker, B.; and L. Visser.Self-Reported Indications for Antidepressant Use in a Population-Based Cohort of Middle-Aged and Elderly.Int J Pharmacol. 2016;38(5):1311-7. DOI: 10.1007/s11096-016-0371-9.Caldwell, P.; Sureshkumar, P.; and W. Wong.Tricyclic and Related Drugs for Nocturnal Enuresis in Children.Cochrane Database Syst Rev.2016;20(1): CD002117. DOI: 10.1002/14651858.CD002117.pub2.Gillman, P.Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.Br J Pharmacol.2007;151(6):737-48. DOI: 10.1038/sj.bjp.0707253.Jobski, K., Schmidt, N., Kolkhorst, B., Krappweis, J., Schink, T., and E. Garbe.Characteristics and Drug Use Patterns of Older Antidepressant Initiators in Germany.Eur J Pharmacol. 2017:73(1):105-13. DOI: doi.org/10.1007/s00228-016-2145-7.

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Massachusetts General Hospital.Somber Questions.Anxiety and Depression Association of America.Medication.National Center for Biotechnology Information.Depression: How effective are antidepressants?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.109.070219U.S. Food and Drug Administration.Pamelor Label.

Massachusetts General Hospital.Somber Questions.

Anxiety and Depression Association of America.Medication.

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

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

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

Aarts, N.: Noordam, R.; Hofman, A.; Tiemeier, J.; Stricker, B.; and L. Visser.Self-Reported Indications for Antidepressant Use in a Population-Based Cohort of Middle-Aged and Elderly.Int J Pharmacol. 2016;38(5):1311-7. DOI: 10.1007/s11096-016-0371-9.Caldwell, P.; Sureshkumar, P.; and W. Wong.Tricyclic and Related Drugs for Nocturnal Enuresis in Children.Cochrane Database Syst Rev.2016;20(1): CD002117. DOI: 10.1002/14651858.CD002117.pub2.Gillman, P.Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.Br J Pharmacol.2007;151(6):737-48. DOI: 10.1038/sj.bjp.0707253.Jobski, K., Schmidt, N., Kolkhorst, B., Krappweis, J., Schink, T., and E. Garbe.Characteristics and Drug Use Patterns of Older Antidepressant Initiators in Germany.Eur J Pharmacol. 2017:73(1):105-13. DOI: doi.org/10.1007/s00228-016-2145-7.

Aarts, N.: Noordam, R.; Hofman, A.; Tiemeier, J.; Stricker, B.; and L. Visser.Self-Reported Indications for Antidepressant Use in a Population-Based Cohort of Middle-Aged and Elderly.Int J Pharmacol. 2016;38(5):1311-7. DOI: 10.1007/s11096-016-0371-9.

Caldwell, P.; Sureshkumar, P.; and W. Wong.Tricyclic and Related Drugs for Nocturnal Enuresis in Children.Cochrane Database Syst Rev.2016;20(1): CD002117. DOI: 10.1002/14651858.CD002117.pub2.

Gillman, P.Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.Br J Pharmacol.2007;151(6):737-48. DOI: 10.1038/sj.bjp.0707253.

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