How Do Tricyclic Antidepressants Work?

Reviewed on 10/5/2021

How Do Tricyclic Antidepressants Work?

Tricyclic antidepressants (TCAs) are some of the earliest medications developed to treat depression and other psychiatric conditions. TCAs derive their name from the three rings of atoms in their molecular structure. TCAs alleviate depression by altering the levels of neurotransmitters in the brain and modulating their activity.

Neurotransmitters are chemicals released by nerve cells (neurons) into the space (synapse) between them to communicate nerve signals. Neurotransmitters bind to protein molecules known as receptors on the adjoining cell surfaces to activate them.

Neurotransmitters enable the regulation of physiological functions such as breathing, heart rate and digestion, and are also responsible for learning, memory, sleep, emotions and behavior. Imbalance in certain neurotransmitters can disrupt normal neurotransmission of signals, resulting in depression, anxiety and other disorders.

TCAs increase the levels of serotonin and norepinephrine by preventing their reabsorption (reuptake), a natural process in the brain. The functions of serotonin include regulation of sleep, digestion, cognition, mood and behavior, and increasing their levels helps in relieving depression and anxiety.

TCAs also block histamine receptors and some of them are used to treat chronic itching. Additionally, TCAs block the activity of acetylcholine, a neurotransmitter that makes muscles contract, which is useful for muscle relaxation and sedation.

TCAs have a lower threshold for overdose compared to more advanced antidepressants, and also a higher risk for suicide ideation. With the development of newer classes of antidepressants with better side effect profiles, currently, TCAs are used as second-line treatment for depression.

How Are Tricyclic Antidepressants Used?

Tricyclic antidepressants are oral tablets, capsules or solutions approved by the FDA for the treatment of the following conditions:

Off-label uses include:

What Are Side Effects of Tricyclic Antidepressants?

Side effects of tricyclic antidepressants may include the following:

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

What Are Names of Some Tricyclic Antidepressant Drugs?

Generic and brand names of tricyclic antidepressant drugs include:


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