Tricyclic antidepressants (TCAs): lists, uses, and side effects

Tricyclic antidepressants (TCAs) are a class of antidepressant medications named for their three-ring chemical structure. They’re typically taken as a pill once a day (Moraczewski, 2020).

Tricyclics were one of the first types of antidepressant drugs developed in the late 1950s. With the development of newer antidepressant classes, like selective serotonin reuptake inhibitors (SSRIs), TCAs are not prescribed as often as they used to be.

However, TCAs are still a vital mental health treatment option for people with treatment-resistant depression or those who don’t respond well to other types of antidepressants (Chockalingham, 2019).

Though they’re not prescribed as often as other antidepressants, TCAs are effective in treating depression. One downfall is TCAs are reported to cause more side effects, which is one big reason why they're not typically prescribed as a first-line treatment (Moraczewski, 2020).

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Most TCAs are FDA-approved to treat major depressive disorder (MDD). One TCA called clomipramine is specifically approved to treat obsessive-compulsive disorder (OCD) (Moraczewski, 2020).

Providers use TCAs to treat other conditions, too. They are prescribed off-label for non-FDA-approved conditions including insomnia, anxiety disorders, chronic pain, headaches, panic disorder, nerve pain, fibromyalgia, and childhood bedwetting (Moraczewski, 2020; Schneider, 2019).

There are nine FDA-approved TCAs. Eight are FDA-approved for the treatment of major depressive disorder, and one as we mentioned (clomipramine) is used for OCD and depression (Moraczewski, 2020; Wilson, 2021).

• Amitriptyline

• Amoxapine

• Doxepin

• Desipramine

• Nortriptyline

• Protriptyline

• Imipramine

• Trimipramine

• Clomipramine

Similar to many other antidepressants, TCAs work by affecting levels of neurotransmitters in the brain.

Neurotransmitters are chemicals that act as messengers. They help regulate all the messages your brain sends and receives about your body and the world around it every day. 

TCAs change the levels of certain neurotransmitters in the brain, allowing specific ones like serotonin and norepinephrine to be more available. These drugs also cause other neurotransmitters, such as histamine and acetylcholine, to be less available (Moraczewski, 2020).

In general, TCAs have a higher rate of side effects than other antidepressants. The good news is some of these adverse effects may improve over time (Moraczewski, 2020; Schneider, 2019).

Common side effects of TCAs include constipation, dizziness, and dry mouth. Less common side effects include (Moraczewski, 2020):

• Blurred vision

• Confusion

• Trouble emptying your bladder fully

• Fast heartbeat

• Low blood pressure

• Drowsiness

• Increased appetite

• Weight gain

TCAs seem to have fewer side effects related to sexual dysfunction than other SSRIs like fluoxetine (Wang, 2018).

Unlike other antidepressant medications, TCAs carry a black box warning from the U.S. Food and Drug Administration. It's an important, severe warning indicating these drugs can worsen depression, and increase suicidal thoughts and behaviors in children and young adults (Moraczewski, 2020).

TCAs are safe for most, but certain people should use extra caution before taking them. 

TCAs may lead to congenital birth defects in pregnant women, so talk to a healthcare provider before starting if you're pregnant or trying to conceive. Most TCAs are safe to use during breastfeeding but check with your provider first (Moraczewski, 2020).

TCAs may increase the risk of cardiovascular issues, like heart rhythm problems (arrhythmias), abnormal heartbeat, and even sudden death in people with heart disease. Be sure to talk to your provider if you have any heart health issues or if anyone in your family does, especially coronary artery disease (Moraczewski, 2020).

People with glaucoma, a history of seizures, or trouble emptying their bladder shouldn’t take TCAs as they could worsen those conditions (Moraczewski, 2020).

You should be aware of potential drug interactions with TCAs. 

If you’re already taking another type of drug that raises your serotonin levels––like monoamine oxidase inhibitors (MAOI), SSRIs, or serotonin-norepinephrine reuptake inhibitors (SNRI)––you shouldn’t take TCAs (Moraczewski, 2020). 

Combining drugs that raise your serotonin levels increases your risk for developing serotonin syndrome, a potentially life-threatening condition. Talk to a healthcare provider and let them know about any medications you are taking, either prescription or over-the-counter, to avoid potential drug interactions (Moraczewski, 2020).