What to know about TCAs—including a comprehensive list

What to know about TCAs—including a comprehensive list

Reviewed by:
Divya Khosla, MD
Staff Psychiatrist
at Talkiatry
March 21, 2024
In this article

Sadness, or feeling down, is a part of every life. For people living with depression, those feelings can start to interfere with daily life. There is good news: Depression is treatable. A combination of therapy and medication has been shown to be effective. There are a few different kinds of medications, specifically antidepressants, that psychiatrists use to help treat depression. One class of antidepressants is called TCAs (tricyclic antidepressants). Keep reading for more about what TCAs are, how they work, what side effects they’re associated with, and more.

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What are tricyclic antidepressants and how do they work?

There are certain chemicals in your brain that help you feel good, centered and happy. In people with depression, these chemicals can be out of balance. TCAs are a class of medication FDA-approved to treat major depressive disorder (MDD) by giving your brain access to more of two of those chemicals—serotonin and norepinephrine. Certain TCAs work more on norepinephrine, while others work more on serotonin.

The first TCA, imipramine, was approved in 1959, after Dr. Ronald Kuhn noticed their positive effects on patients with depression. In the following decades, more TCAs were approved. With the development of SSRIs (selective serotonin reuptake inhibitors) and other modern antidepressants, which have fewer side effects than TCAs, TCAs have become what are called second-line treatments for depression. That means your psychiatrist will typically prescribe them only after other medications have failed to lessen your symptoms. Still, TCAs may potentially be about as effective as SSRIs at treating depression.

Other conditions treated

Clinicians also sometimes prescribe tricyclic antidepressants off-label, meaning for conditions they’re not FDA-approved to treat, but have shown effective results. Some of those conditions include anxiety, certain kinds of nerve pain, and fibromyalgia, as well as migraine prevention. Children, meanwhile, may be prescribed them to relieve bedwetting. One TCA, clomipramine, is also FDA-approved to treat OCD, or obsessive-compulsive disorder.

Which medications are TCAs?

Here are a list of common TCAs (generic names first and their brand names) that are FDA-approved to treat symptoms of depression.

  • Amitriptyline (Elavil, Vanatrip): Prescribed off-label for certain kinds of chronic pain, gibromyalgia, headaches, anxiety, and insomnia
  • Amoxapine (Asendin): Prescribed off-label for chronic pain, anxiety, insomnia  
  • Doxepin (Silenor, Sinequan): Prescribed off-label for chronic pain, anxiety, and insomnia (Silenor)  
  • Desipramine (Norpramin): Prescribed off-label for chronic pain, anxiety, insomnia
  • Imipramine (Tofranil, Tofranil-PM): Prescribed off-label for chronic pain, anxiety, insomnia, and bedwetting in children
  • Nortriptyline (Aventyl, Pamelor): Prescribed off-label for ADHD, chronic pain, insomnia, anxiety
  • Protriptyline (Vivactil)
  • Trimipramine (Surmontil): Prescribed off-label for chronic pain, insomnia, anxiety

Clomipramine (Anafranil), meanwhile, is unique among TCAs in that it’s FDA-approved solely for the treatment of OCD in patients aged 10 and older.  

Keep in mind that the specific effects of TCAs can vary. If you and your psychiatrist agree that starting a TCA is right for you, your psychiatrist will review all your health details (including your age and liver, kidney, and heart health) to determine which medication makes the most sense.  

Related article: How to get depression medication

Do people still take TCAs?

While effective, TCAs are no longer considered first-line medications for the treatment of depression because other medications, such as SSRIs and SNRIs (serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors), may potentially be as effective and have fewer and less severe adverse effects. Still, your psychiatrist may prescribe you tricyclic antidepressants if your depression doesn’t get better with SSRIs alone, or for other reasons related to your situation and medical history. You and your psychiatrist will work together to develop a detailed treatment plan that takes into account all the particularities of your circumstances.  

In general, you’re more likely to be prescribed TCAs today for those “off-label” uses we described above than you are for depression. Long story short, people do indeed still take TCAs.

Side effects of tricyclic antidepressants

TCAs are associated with a number of side effects, some of them fairly common, some of them less so. We’ll list examples from both categories, as well as other useful information, below.  

Common side effects:

  • Constipation
  • Dizziness
  • Dry mouth
  • Drowsiness
  • Blurred vision
  • Difficulty passing urine
  • Weight gain
  • Heart rhythm issues (arrhythmia), including a fast heartbeat and noticeable palpitations  

Less common side effects:

  • Cardiac arrest in patients with certain kinds of heart disease
  • Seizures, especially in patients with epilepsy
  • Increased suicidal thoughts, especially in patients aged 24 or younger

If you’re worried about any of these be sure to chat with your doctor, who will help you know what to look out for and how to minimize risks.

Precautions and considerations

Your doctor will also look at any other conditions (like a history of seizures or heart disease) you may have in determining if TCAs are right for you. For example, TCAs should be used in caution in people with renal impairment, hepatic impairment, cardiac impairment, older people, people with glaucoma, pregnant people, and people that are breastfeeding. You should discuss potential benefits, risks, side effects, and alternative options with your doctor.

Before prescribing you medication, your physician will also look at what other medications you take, particularly those relating to mental health, to make sure TCAs will be safe for you. Tricyclic antidepressants are generally not prescribed at the same time as SSRIs, for example, as the combination may result in serotonin syndrome, a condition in which too much serotonin in the brain can cause diarrhea and a number of other issues.  

Other medications that can have negative effects on your health if taken alongside TCAs include, lithium, anticoagulants, blood pressure medications, and SNRIs.

Do TCAs work quickly?  

The precise amount of time it takes TCAs (and other antidepressant medications) to work can vary depending on the dose prescribed and differences among individuals. If you’re taking tricyclic antidepressants for depression, you may start to see improvements in 2-4 weeks, but changes could occur earlier or later than that. Your psychiatrist will typically prescribe smaller doses when you start medication to see how you react to it. Depending on the results, and your needs, they may increase your dosage up to a maximum, that varies from one TCA to another.

If you miss a dose of medication, do not double your dosage the next day. If only a few hours have passed, however, you may go ahead and take it. Remember you can always reach out to your psychiatrist if you have any specific questions about what to do.

The half-life of tricyclic antidepressants, or the time it takes for the amount of medication in your system to decrease by half after ingestion, varies from about 10 to 50 hours depending on the specific TCA. That means that missing a dose will result in a lower concentration of the drug in your bloodstream. Some TCAs have a longer-lasting effect, meaning they stay in your system for a significant amount of time, but others won’t. This means that withdrawal symptoms could kick in earlier for certain TCAs, while for others, it might take a bit longer. When you stop taking antidepressants, your doctor will help you taper off the medication to minimize risks of withdrawal.

How long do you have to take them?

A major question many people have when starting a new medication is: How long do I have to keep taking whatever I’ve been prescribed? It’s safe to stay on antidepressants for the long term and also safely stop them when you’re feeling better and back to your old self. Once you and your clinician decide you’re ready to stop taking antidepressants they can gradually taper your dosage until you’re ready to come off the medication completely.  

Stopping your medications too soon can carry significant risks, including the return of depression symptoms, which may actually be worse than before treatment began. Additionally, if you resume taking a TCA after stopping, its effects may differ the second time around.  

As a general rule, you shouldn’t just decide to stop taking medications, including TCAs, on your own. Instead, you should talk with your psychiatrist to decide when, how, and whether to stop.  

To learn more about what happens after you stop taking medication, check out: Can I start antidepressants after stopping?

Other types of antidepressants

As mentioned previously, TCAs are considered a second-line medication for treating depression, meaning they’re generally only prescribed after first-line medications (like SSRIs) fail to relieve symptoms. In addition to SSRIs and TCAs, there are several other types of antidepressants, including the following:

  • SNRIs (Serotonin-norepinephrine reuptake inhibitors): Like TCAs, these medications keep more serotonin and norepinephrine in your brain. They have a more focused effect than TCAs, however, which also block the receptors of other neurochemicals. SNRIs also have fewer and less severe side effects. Examples include duloxetine (Cymbalta) and venlafaxine (Effexor XR), among others.  
  • Atypical antidepressants: As the name implies, these medications each work differently and don’t slot in easily with other types of antidepressants. Examples include trazodone and bupropion (Wellbutrin).  
  • MAOIs (Monoamine-oxidase inhibitors): While MAOIs are the first type of antidepressant, they are now only typically prescribed when other treatment options don’t work. This is because of the severe side effects of MAOIs.  

There are also a few other kinds of antidepressants, as well as medications your psychiatrist might prescribe to work in conjunction with antidepressants. Generally, a combination of talk therapy and medications is more effective than medications alone.  

If you think you have depression, it’s important to talk with a healthcare professional about how you’re feeling. If you’re unsure where to start, take Talkiatry’s quick assessment. We’ll help match you with a psychiatrist who’ll work with you to determine a proper treatment plan.  


What is the difference between a TCA and an SSRI?

SSRIs, like Prozac (fluoxetine) increase the amount of serotonin in synapses, the spaces between neurons through which chemical and electrical signals pass. TCAs have a broader effect, increasing serotonin and norepinephrine levels, while also blocking receptors related to a number of other neurotransmitters. Clinicians tend to prescribe TCAs only to patients for whom SSRIs haven’t worked, as the potential adverse effects of TCAs are greater in number and severity than those associated with SSRIs.

What are some common TCAs?

TCAs, all of which have been approved to treat depression include Elavil, Tofranil, Vanatrip, Asendin, Norpramin, Silenor, SINEquan, Aventyl, Vivactil, and Surmontil.  

What is the biggest risk associated with tricyclic antidepressants?

When taking TCAs, you may experience an increase in suicidal thoughts, especially if you’re 24 or younger. This is a risk of some other antidepressants, too, just TCAs. There is also a risk of cardiac arrythmias, sedation leading to coma, and seizures. If you’re taking TCAs your doctor will help you minimize these risks.  

Can TCAs cause weight gain?

Yes, TCAs can cause increased appetite and weight gain as a result, but individual responses, as well as the effects of different TCAs, can vary. If you have concerns about weight changes while on antidepressants, speak to your doctor.  You can also check out: Can antidepressants cause weight loss?

If you’ve been experiencing symptoms that seem like depression, or if you have other conditions for which you think TCAs might be appropriate, your first step should be consulting a qualified professional.  One way to start is by taking Talkiatry’s quick assessment. We’ll make sure we’re the right fit for you and match you with a psychiatrist who can help with your specific needs.

The information in this article is for education and informational purposes only and should never be substituted for medical advice, diagnoses, or treatment. If you or someone you know may be in danger, call 911 or the National Suicide and Crisis Lifeline at 988 right away.

Dr. Divya Khosla, MD, is a board certified Adult Psychiatrist and board eligible Child and Adolescent Psychiatrist. She received her undergraduate degree from Case Western Reserve University in Cleveland, Ohio, and her medical degree from Ross University, completing all of her clinicals in Maryland, D.C., and NYC. She completed her adult psychiatry residency at The Ohio State University in Columbus, Ohio. Then she returned to the east coast, where she completed her child and adolescent psychiatry fellowship at Nassau University Medical Center in East Meadow, New York.

Dr. Khosla has participated in a variety of innovative academic clinical research, and has presented research at annual national meetings of the American Psychiatric Association. Her robust clinical experience with varying demographics at different clinical sites around the country has allowed her to treat patients in an evidence-based way, tailoring treatment to an individual’s specific needs.

Although Dr. Khosla’s practice focuses on medication management, she also implements supportive therapy and motivational interviewing in sessions to allow for a more comprehensive approach to treatment. Her clinical interests include depression, bipolar disorder, anxiety disorders, post-traumatic stress disorder, panic disorder, and ADHD.

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