Tricyclic antidepressants (TCAs), which people also call cyclic antidepressants, are an older type of antidepressant that doctors prescribe to treat depression. Doctors prescribe them less frequently than other types of antidepressants due to their possible side effects. However, TCAs can be suitable for people who have found other medications ineffective.

TCAs affect chemical messengers in the brain. They block the reabsorption of the neurotransmitters norepinephrine and serotonin. In doing so, they increase the levels of both of these neurotransmitters in the brain, which helps improve a person’s mood.

TCAs can be effective, but they may cause a lot of side effects, which can range from mild to severe. Due to this, doctors will generally recommend other antidepressants before prescribing TCAs. If other treatments are unsuitable or ineffective, though, TCAs may be a good option for some people.

In this article, we look at the currently available TCAs and their side effects and risks, including any potential interactions with other drugs or health conditions.

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TCAs that the Food and Drug Administration (FDA) has approved for sale and use include:

  • amitriptyline (Elavil)
  • amoxapine (Asendin)
  • desipramine (Norpramin)
  • doxepin (Sinequan)
  • imipramine (Tofranil)
  • nortriptyline (Pamelor)
  • protriptyline (Vivactil)
  • trimipramine (Surmontil)

TCAs are an older type of antidepressant medication that first came into use in 1959 to treat major depressive disorder (MDD).

TCAs are as effective as selective serotonin reuptake inhibitors (SSRIs), a newer type of antidepressant, but they have significantly more side effects.

For this reason, doctors do not usually prescribe TCAs as a first-line treatment for depression. TCAs may be a suitable option when other treatments are not effective, though.

Doctors may sometimes also prescribe TCAs to treat:

People may take TCAs orally as a tablet, capsule, or solution. In some cases, TCAs may come in the form of patches or topical ointments.

Common side effects of TCAs include:

Less common side effects include:

  • difficulty urinating
  • confusion
  • fainting
  • seizures
  • an irregular heartbeat, which can be life threatening

People may tolerate some tricyclics better than others. Amitriptyline and nortriptyline may cause these additional side effects:

  • sedative effects
  • increased sweating
  • sodium imbalance, which may cause nausea, confusion, or headaches
  • weight gain
  • heart rhythm disturbances

Some people may tolerate desipramine better than amitriptyline.

High levels of TCAs are toxic, and an overdose of TCAs can be fatal, so it is important to take the medication exactly as a doctor prescribes.

Research has shown an increased risk of suicidal thoughts and behavior in people aged 24 years or under in the initial stages of taking TCAs.

It is important that healthcare professionals closely monitor people taking TCAs in the initial stages of treatment or during a dosage increase. The FDA requests that all antidepressant medications include a warning of this risk on their labels.

TCAs can interact with certain other medications and herbal supplements, which can be dangerous and even life threatening.

Combining tricyclic antidepressants with any serotonin-enhancing products could cause a dangerous elevation in serotonin and lead to a life threatening condition called serotonin syndrome. These products include:

The symptoms of serotonin syndrome include:

  • dilated pupils
  • hyperreflexia, a condition in which people have overresponsive or overactive reflexes
  • muscle spasms
  • tremors
  • diarrhea
  • confusion

A person with any symptoms of serotonin syndrome will require immediate medical attention.

Taking TCAs with monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping them, can be dangerous.

Other medications that can interact negatively with TCAs include:

People will also need to be cautious if they use sedative substances, including alcohol, alongside TCAs.

In people with existing heart conditions, TCAs may cause complications. In severe cases, these drugs may lead to sudden cardiac death in people with existing heart disease.

TCAs may also increase seizure risk in people who have epilepsy. Research has shown mild elevation of liver enzymes with the use of TCAs, although the risk of acute hepatitis with TCAs is rare.

People will need to discuss the safety of using TCAs if they have any existing medical condition, including:

  • glaucoma
  • enlarged prostate
  • heart conditions
  • diabetes
  • liver disease
  • history of seizures
  • urinary retention
  • overactive thyroid gland
  • drug-related high fever

Tricyclic antidepressants can affect each individual differently, and a person’s lifestyle, age, medical history, and overall health will determine which medication is best for them.

People can discuss any concerns and potential side effects with their doctor to find a treatment that will suit them.

The doctor will need to be aware if a person is pregnant, planning to become pregnant, or nursing. Using TCAs during pregnancy can cause birth abnormalities, and clomipramine may cause heart problems in a newborn.

TCAs, except doxepin, are safe to use during breastfeeding, and research has not shown them to cause adverse effects. Nortriptyline may be the safest due to it having no sedative effects.

If people are experiencing side effects from taking TCAs, they will need to talk with their doctor before stopping or changing any medication.

Withdrawal can cause side effects, so it is important that people work alongside a healthcare professional to reduce their dosage gradually.

People can contact a doctor straight away or seek medical help if they have any of the following side effects:

  • suicidal thoughts
  • attempted suicide
  • new or worsening anxiety or depression
  • high levels of agitation or restlessness
  • panic attacks
  • difficulty sleeping
  • new or worsening mood changes, such as irritability, anger, aggressive behavior, or violence
  • impulsiveness and taking dangerous actions
  • extreme increase in energy levels, activity, and talking, known as mania

Anyone who feels suicidal or believes that they pose a risk to themself or others should go to the emergency room or call the toll-free National Suicide Prevention Lifeline on 800-273-TALK (8255).

TCAs are an effective antidepressant medication, but they can cause a range of side effects, some of which are severe. Due to this, a doctor may prescribe alternative medication first. If other treatments are not effective, TCAs may be the best treatment for some people.

TCAs can increase the risk of suicidal thoughts or behavior in the first stages of treatment or with an increase in dosage, particularly in people aged 24 years or younger. Close monitoring from a healthcare professional is essential during this phase.

If a person experiences any serious side effects, suicidal thoughts, or extreme mood changes, they should seek medical help straight away.