Tricyclic antidepressants

Date Updated: 10/08/2024

Tricyclic antidepressants are among the earliest antidepressants developed. They're effective, but they've generally been replaced by antidepressants that cause fewer side effects. Tricyclic antidepressants may be a good option for some people. In certain cases, they ease depression when other treatments have failed.

How tricyclic antidepressants work

Tricyclic antidepressants ease depression by affecting chemical messengers called neurotransmitters. These chemical messengers communicate between brain cells. Like most antidepressants, tricyclic antidepressants work by causing changes in brain chemistry and communication in brain nerve cell circuitry known to affect mood. This helps lessen the symptoms of depression.

Tricyclic antidepressants block the neurotransmitters serotonin (ser-o-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin) from being taken back into nerve cells in the brain, a process called reuptake. Blocking reuptake raises the levels of these two neurotransmitters in the brain. Tricyclic antidepressants also affect other chemical messengers, which can lead to some of the antidepressants' side effects.

Tricyclic antidepressants approved to treat depression

The U.S. Food and Drug Administration, also called FDA, approved several tricyclic antidepressants to treat depression. Examples include:

Amitriptyline.
Desipramine (Norpramin).
Doxepin.
Imipramine.
Nortriptyline (Pamelor).
Protriptyline.

Sometimes tricyclic antidepressants are used to treat conditions other than depression. For example, the FDA approved clomipramine (Anafranil) to treat obsessive-compulsive disorder and imipramine to treat childhood bed-wetting. Some tricyclic antidepressants also are used to treat anxiety disorders and nerve-related pain called neuropathic pain and to prevent migraines.

Tricyclic antidepressants are a type of cyclic antidepressant. This type also includes tetracyclic antidepressants. Cyclic antidepressants are grouped depending on the number of rings in their chemical structure — three (tri) or four (tetra). In the United States, currently the FDA does not approve any tetracycline antidepressant to treat depression.

Possible side effects and cautions

Because of the different ways tricyclic antidepressants work, side effects vary somewhat from medicine to medicine. Some side effects may go away after a time. Others may lead you and your healthcare professional to try a different medicine. Side effects also may depend on the dose. Higher doses often cause more side effects.

Some common possible side effects include:

Drowsiness.
Blurred vision.
Constipation.
Dry mouth.
Drop in blood pressure when moving from sitting to standing, which can cause lightheadedness.
Problems passing urine.

Other possible side effects include:

Weight loss.
Urges to eat more, leading to weight gain.
Too much sweating.
Shakiness, also called tremor.
Sexual problems, such as trouble getting an erection, delayed orgasm or low sex drive.

Generally speaking:

Amitriptyline, doxepin, imipramine and trimipramine are more likely to make you sleepy than other tricyclic antidepressants are. Taking these medicines at bedtime may help.
Amitriptyline, clomipramine, doxepin, imipramine and trimipramine are more likely to cause weight gain than other tricyclic antidepressants are.
Nortriptyline and desipramine seem to have better tolerated side effects than other tricyclic antidepressants do.

For antidepressants that cause sleepiness, be careful about doing activities that require you to be alert until you know how the medicine will affect you. This can include not driving a car or operating heavy machinery such as construction equipment.

Which antidepressant is best for you depends on several factors, such as your symptoms and any other health conditions you may have. Ask your healthcare professional and pharmacist about the most common possible side effects for the antidepressant prescribed for you. Also read the patient medicine guide that comes with the prescription.

Safety issues

Some tricyclic antidepressants are more likely to cause side effects that affect safety. These side effects include:

Disorientation or confusion, especially in older people when the dose is too high.
Heartbeat that is too fast or not regular.
Seizures that happen more often in people who have seizures.

Before you take a tricyclic antidepressant, talk with your healthcare professional about:

Antidepressants and pregnancy. Talk to your healthcare professional about the risks and benefits of using specific antidepressants. Some antidepressants may harm your baby if you take them during pregnancy or while you're breastfeeding. If you're taking an antidepressant and you're considering getting pregnant, talk with your healthcare professional about the possible risks. Don't stop taking your medicine without talking to your healthcare professional first. Stopping an antidepressant might put you at risk of withdrawal-like symptoms or returning depression.
Interactions with other medicines and supplements. When taking an antidepressant, tell your healthcare professional about any other prescription or nonprescription medicines, herbs or other supplements you're taking. Some antidepressants can cause dangerous reactions when combined with some medicines or herbal supplements.
Serotonin syndrome. Rarely, an antidepressant can cause high levels of serotonin to build up in your body. Serotonin syndrome most often happens when two medicines that both raise the level of serotonin are taken together. These include other antidepressants, some pain or headache medicines, and the herbal supplement St. John's wort.

Symptoms of serotonin syndrome include anxiety, nervousness, high fever, sweating, confusion, tremors, restlessness, lack of coordination, major changes in blood pressure and a fast heartbeat. Get medical care right away if you have any of these symptoms.
Safety and blood tests. Your healthcare professional may recommend blood tests to measure the medicine levels to decide on the most effective dose. Some side effects and benefits of tricyclic antidepressants depend on the dose. Overdose of tricyclic antidepressants can be dangerous.
Long-term health conditions. Tricyclic antidepressants can cause problems in people with certain health conditions. For example, if you have narrow-angle glaucoma, an enlarged prostate, heart problems, diabetes or a history of seizures, talk with your healthcare professional to decide if a tricyclic antidepressant is a safe choice for you.

Suicide risk and antidepressants

Most antidepressants are generally safe, but the FDA requires that all antidepressants carry boxed warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under 25 may have an increase in suicidal thoughts or behavior when taking antidepressants. This may be more likely in the first few weeks after starting the medicine or when the dose is changed. There has been no evidence that this increase in suicidal thoughts or behaviors has resulted in completed suicides.

Anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior. If you or someone you know has suicidal thoughts when taking an antidepressant, call your healthcare professional right away or get emergency help.

Keep in mind that depression that's not treated is a more concerning risk factor for suicide. And antidepressants may lessen suicide risk in the long run by improving mood for many people.

Stopping treatment with tricyclic antidepressants

Tricyclic antidepressants aren't considered habit-forming. But suddenly stopping antidepressant treatment or missing several doses can cause withdrawal-like symptoms. Symptoms may vary depending on how the medicine works. This is sometimes called discontinuation syndrome. Work with your healthcare professional to slowly and safely lower your dose over time.

Withdrawal-like symptoms can include:

Restlessness, irritability or anxiety.
Upset stomach.
Feelings of tingling or burning.
Flu-like symptoms, such as chills, sweating and muscle aches.
Trouble sleeping.
Sluggishness, tiredness or sleepiness.
Headache.
Dizziness.

Finding the right antidepressant

People may react differently to the same antidepressant. For example, one medicine may work better — or not as well — for you than for another person. Or you may have more, or fewer, side effects from taking a specific antidepressant than someone else does.

Traits passed down in your family may play a role in how antidepressants affect you. In some cases, where available, results of special blood tests may offer clues about how your body may respond to a specific antidepressant. Pharmacogenomics — the study of how drugs work coupled with information about human genes — is sometimes available to tailor medications and their doses for people based on their genetic makeup. But other things besides genetics can affect your response to medicine.

When choosing an antidepressant, your healthcare professional considers your symptoms, any health problems, other medicines you take, and what's worked for you in the past.

Typically, it may take several weeks or longer before an antidepressant fully works and for early side effects to ease up. Your healthcare professional may recommend some dose changes or different antidepressants. With patience, you and your healthcare professional can find a medicine that works well for you.