8 Tricyclic Antidepressant (TCA) Side Effects: Dizziness, Dry Mouth, and More
Key takeaways:
Tricyclic antidepressants (TCAs) are a class of prescription medications. They’re most often used to treat depression, but many of them are also prescribed off-label for other conditions.
Dry mouth is the most common TCA side effect overall. Other side effects include dizziness, constipation, and fatigue. Rare but serious side effects of TCAs include heart rhythm problems and thoughts of suicide or self-harm.
Due to slight differences in their chemical structure, some side effects are more likely with certain TCAs. In general, “secondary amine” TCAs, such as nortriptyline (Pamerlor), are better tolerated than other TCAs.
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Table of contents
Tricyclic antidepressants (TCA) are a group of medications that have been around for decades. These medications are FDA approved to treat depression, but they’re also frequently prescribed off-label for other health conditions, such as chronic pain, insomnia, and nerve pain.
This class of antidepressants includes a number of medications — some prescribed more often than others. Popular TCAs that you may be familiar with are amitriptyline, doxepin (Silenor, Zonalon, Prudoxin), and desipramine (Norpramin).
Although TCAs have been around for a while, they aren’t typically recommended as a first-choice treatment for depression. This is because they can cause a variety of side effects, including some potentially serious ones.
TCA side effects at a glance
Not all TCAs are created equally. Some TCAs are more likely to cause side effects than others.
The reason for this is related to their chemical structure. Some TCAs have what’s called a secondary amine structure, while others have a tertiary amine structure. Examples of secondary amine TCAs include desipramine, nortriptyline (Pamelor), and protriptyline. Examples of tertiary amine TCAs include amitriptyline and doxepin. As a general rule, healthcare professionals consider secondary amine TCAs easier to tolerate.
Common TCA side effects overall include:
Dizziness
Drowsiness
Dry mouth
Constipation
Weight gain
Sexual changes
Changes in eye pressure
TCAs explained: Here are the essential facts about tricyclic antidepressants (TCAs).
Antidepressant overview: Many medications can treat depression aside from TCAs. Learn more about the many treatment options that are out there.
Boxed warnings: Read on to learn what they are and why they’re so important for medication safety.
Rare but serious side effects of TCAs include:
Seizures
Heart rhythm problems
Thoughts of self harm or suicide
Let’s get an in-depth look at eight notable TCA side effects and ways to manage them.
1. Dry mouth
If you feel like you have a sticky or dry mouth while taking a TCA, you’re not alone. Dry mouth is one of the most common side effects of TCAs. Nearly one-third of people taking TCAs experience dry mouth.
Thankfully, there are a number of ways to manage dry mouth. Start off by drinking more water. The ideal amount of water you should drink varies by person, but being better hydrated can help alleviate dry mouth. Chewing sugar-free gum is another quick at-home remedy you can try to help with dry mouth.
If those options don’t quite cut it, there are a number of over-the-counter (OTC) products you can try. OTC saliva substitutes, such as Biotene and Bioextra, can make a difference. But if you’re still experiencing dry mouth symptoms, talk to your healthcare professional about trying a prescription dry mouth medication, such as pilocarpine (Salagen) or cevimeline (Evoxac).
2. Dizziness
Dizziness is another common side effect of TCAs. Most cases of dizziness result from something called orthostatic hypotension, or a drop in blood pressure when you’re changing positions.
This side effect occurs because of the way TCAs work. Specifically, by blocking a certain receptor (binding site) in your body called the alpha-1 adrenergic receptor. Some TCAs are more likely to cause dizziness than others because of how they bind to this receptor. TCAs that are known to cause dizziness include doxepin, amitriptyline, and imipramine.
If you’re feeling dizzy, it’s important to find a safe place to sit or lie down to prevent falling. Drinking water or having a snack may help to alleviate some of your dizziness as well.
If your dizziness becomes bothersome, persistent, or severe, talk to your prescriber about it. They may want to adjust your dose or switch you to a different medication altogether.
3. Constipation
Constipation is a common problem linked to many medications — TCAs included. Just over a fifth of people taking TCAs experience constipation.
Fortunately, there are several ways to manage constipation while taking a TCA. At-home remedies include drinking more water, gradually increasing your fiber intake, and exercising regularly.
If these don’t do the trick, there are a number of laxative medications to consider. Many are available, so ask your pharmacist for a recommendation. They may tell you to start with one laxative, and add on another until you get relief. Popular examples of OTC laxatives include senna (Senokot, Ex-Lax), docusate sodium (Colace, DocQLace), and polyethylene glycol (Miralax, Glycolax).
4. Fatigue
Fatigue, or feeling drowsy or tired, is another common TCA side effect. While this can be inconvenient, it's also why some TCAs are used off-label to treat insomnia. They can also help improve sleep quality in people living with chronic fatigue syndrome.
TCAs with a tertiary amine structure, such as amitriptyline and doxepin, are notorious for leaving you feeling extra tired. If you’re looking for a TCA that tends to cause less fatigue, ask your prescriber about an alternative you could try, such as desipramine, nortriptyline, or protriptyline.
You can also try taking your medication at bedtime as a way to help fight some of the fatigue. Remember that it may just take some time to get used to your medication. If the fatigue hasn’t subsided after a few weeks, ask your prescriber about reducing your dose or trying another medication.
5. Weight gain
TCAs may cause weight gain. This is because of their effect on appetite.
Similar to other side effects, some TCAs are more well-known for this than others. Weight gain tends to occur more with tertiary amine TCAs, including amitriptyline, doxepin, and clomipramine (Anafranil).
If you’re gaining unwanted weight while taking a TCA, talk to your healthcare professional about switching to one that doesn’t have as much of an effect on body weight, such as desipramine or nortriptyline.
6. Sexual changes
Sexual problems may arise while taking a TCA. Approximately one-third of people taking a TCA experience issues such as erectile dysfunction (ED) or negative impacts on sex drive.
Some TCAs that have been linked to ED include amitriptyline, imipramine, and doxepin, among others. Other TCAs that are known to cause sexual side effects include nortriptyline and clomipramine.
In many cases, this side effect is temporary. If you’re still experiencing issues after this, talk to your prescriber about switching to another antidepressant that is less likely to have this effect, such as buspirone or bupropion (Wellbutrin XL, Wellbutrin SR).
7. Heart rhythm problems
Some people experience changes in their heart rhythm, including reports of QT prolongation, while taking a TCA. This is especially true when TCAs are taken at higher doses.
Although all TCAs can cause this issue, tertiary amine TCAs are especially problematic in people with heart conditions.
To be safe, your healthcare professional will likely avoid prescribing you a TCA if you recently had a heart attack or have any heart rhythm problems. Make sure your prescriber is aware of any past heart issues you have or if you have a family history of heart problems.
8. Thoughts of suicide and self-harm
Another rare but serious side effect of TCAs is thoughts of suicide or self-harm. This isn’t specific to TCAs, though. All antidepressants have a boxed warning, which means they can increase the risk of having suicidal thoughts or behaviors while taking them. These risks are higher for people under 25 years old.
If you experience any unusual thoughts or behaviors when taking a TCA, report them to your prescriber right away.
If you or someone you know is having thoughts of suicide, you’re not alone, and help is available. Call the 988 Suicide & Crisis Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.
The bottom line
Tricyclic antidepressants (TCAs) are a group of prescription antidepressants. Common TCA side effects include dry mouth, dizziness, and constipation. More serious side effects, though they’re rare, include heart rhythm problems and thoughts of suicide or self harm.
Some side effects are more frequently seen with certain TCAs due to their chemical structure. “Secondary amine” TCAs (i.e., desipramine, nortriptyline, and protriptyline) tend to be better tolerated than tertiary amine TCAs (i.e., amitriptyline, clomipramine, and doxepin).
If you’re experiencing any bothersome or long-lasting side effects from a TCA, contact your prescriber right away. And listen to your body; call 911 or go to the nearest ER if something feels serious.
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References
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Elsevier Mental and Behavioral Health. (2024). Tricyclic antidepressants (TCAs).
Higgins, A., et al. (2010). Antidepressant-associated sexual dysfunction: Impact, effects, and treatment. Drug, Healthcare and Patient Safety.
Moraczewski, J., et al. (2023). Tricyclic antidepressants. StatPearls.
Schneider, J., et al. (2019). Beyond depression: Other uses for tricyclic antidepressants. Cleveland Clinic Journal of Medicine.
Trindade, E., et al. (1998). Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: A meta analysis. Canadian Medical Association Journal.
