Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) are medications that are FDA-approved to treat symptoms of major depressive disorder. But healthcare providers more often prescribe them for other conditions, such as chronic pain and insomnia. This is considered an off-label use of the medication.


What are tricyclic antidepressants?

Tricyclic antidepressants (TCAs) are a class of medications that help manage the symptoms of clinical depression (major depressive disorder). Healthcare providers prescribe them for other conditions as well.

TCAs are one of many classes of antidepressants. They were one of the first types of antidepressants invented and are considered “first-generation” antidepressants.

Today, providers more commonly prescribe TCAs for off-label use than for depression. This is because there are other classes of antidepressants for depression that are generally safer and have fewer adverse side effects.

Tricyclic antidepressants get their name from their chemical structure, which contains three rings with one side chain.

What are the types of tricyclic antidepressants?

The following are all the tricyclic antidepressants (and their brand names) that are approved by the Food and Drug Administration (FDA) to treat major depressive disorder:

Clomipramine (Anafranil®) is another TCA that’s FDA-approved for obsessive-compulsive disorder (OCD) in people aged 10 and older.


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What conditions do tricyclic antidepressants help treat?

Tricyclic antidepressants are FDA-approved to treat major depressive disorder and other depressive disorders. However, healthcare providers rarely choose TCAs as the first option for treating depression symptoms. This is because there are safer antidepressant options, such as SSRIs. Providers may only prescribe TCAs for depression if other antidepressants aren’t working, since TCAs may be more effective for some people. One potential exception is OCD, as providers consider the TCA clomipramine to be the gold standard treatment.

Providers more commonly prescribe TCAs for off-label use today. This means that the medication isn’t FDA-approved to treat the condition, but research has shown the medication may be effective in treating it.

The off-label (non-FDA) uses of TCAs include:

What’s the difference between SSRIs and tricyclic antidepressants?

Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants are both classes of antidepressants. TCAs are considered “first-generation” antidepressants, and SSRIs are considered “second-generation” antidepressants.

They’re both effective in improving the symptoms of major depressive disorder. But healthcare providers more commonly prescribe SSRIs than TCAs because TCAs cause more significant adverse side effects. In addition, overuse of TCAs can more easily result in toxicity and overdose.


Procedure Details

How do tricyclic antidepressants work?

Tricyclic antidepressants work by increasing the levels of norepinephrine (primarily) and serotonin in your brain. These chemicals are called neurotransmitters. Norepinephrine and serotonin play an important role in regulating your mood and behavior.

Through this process, TCAs also block certain receptors in your body, which ultimately causes adverse side effects, such as dry mouth and urinary retention.

Healthcare providers sometimes prescribe TCAs to manage chronic pain. Researchers think that TCAs relieve pain by blocking pain signals in your spinal cord and by blocking peripheral pain signals through complex anti-neuroimmune actions.

How do you take tricyclic antidepressants?

TCAs are available in the form of oral tablets, capsules and solutions.

The dosages for each type of TCA vary. As TCAs have a high risk of adverse effects and toxicity, your healthcare provider will initially prescribe the lowest dose possible and gradually increase it if necessary.


Risks / Benefits

What are the side effects of tricyclic antidepressants?

Each type and brand of tricyclic antidepressant has its own side effects. Be sure to talk to your healthcare provider or pharmacist about possible side effects to look out for.

In general, common side effects of tricyclic antidepressants include:

Other side effects of TCAs may include:

What are the risks or complications of tricyclic antidepressants?

Tricyclic antidepressants may not be suitable under certain situations, including:

  • If you have heart disease: TCAs may cause cardiovascular complications in people with preexisting ischemic heart disease. To assess cardiac risk, your provider may order an electrocardiogram (EKG) before starting a TCA.
  • If you have epilepsy: TCAs may also increase the risk of seizures in people with epilepsy.
  • If you’re pregnant or thinking of becoming pregnant: Healthcare providers generally don’t consider TCAs safe during pregnancy. Studies have shown a correlation between the use of TCAs during pregnancy and birth defects that affect the fetus’s eyes, ears, face and neck.

Talk to your provider if any of these situations apply to you before starting an antidepressant. If you’re currently taking a TCA, they may recommend stopping the medication or switching to a different type of antidepressant.

In some cases, children, teens and adults under the age of 25 may experience an increase in suicidal thoughts or behavior when taking TCAs, especially when they first start them or when they take a different dose.

If you or your child have suicidal thoughts or behavior, call your healthcare provider who prescribed the medication immediately. You can also dial 988 on your phone to reach the Suicide and Crisis Lifeline.

Can tricyclic antidepressants lead to overdose?

Yes, tricyclic antidepressants are among the most common type of antidepressants involved in an overdose. An overdose can happen if you take too much of a tricyclic antidepressant, whether accidentally, unknowingly or intentionally.

Always take your medication as prescribed and store your medications safely away from children and pets. TCA overdoses very rarely happen when you take your medication as prescribed.

Symptoms of tricyclic antidepressant overdose include:

TCA overdose can be fatal if it’s not treated in time. If you ever suspect an overdose — in yourself or a loved one — call 911 and get medical help right away.

Recovery and Outlook

How long does it take for tricyclic antidepressants to work?

If you’re taking a tricyclic antidepressant to treat depression symptoms, it may take two to four weeks to notice the full effect of the medication. Talk to your healthcare provider if you don’t notice a change in your symptoms after four weeks.

When To Call the Doctor

When should I call my healthcare provider?

You should have regular appointments with your healthcare provider when you’re taking a tricyclic antidepressant to assess how well it’s working.

Otherwise, talk to your healthcare provider in the following situations:

  • If you develop bothersome side effects.
  • If your symptoms aren’t improving or if they’ve gotten worse.
  • If you’re thinking of stopping the medication.

When should I seek emergency care?

If you have symptoms of a TCA overdose or are having suicidal thoughts, call 911 or go to the nearest emergency room.

A note from Cleveland Clinic

While tricyclic antidepressants (TCAs) are mainly FDA-approved to treat depression, healthcare providers more often prescribe them to treat other conditions, such as chronic pain. If you have any questions or concerns about taking a TCA, don’t be afraid to ask your healthcare provider. They’re available to help.

Medically Reviewed

Last reviewed on 07/24/2023.

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