Tricyclic Antidepressants
Updated on September 30, 2024
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Tricyclic antidepressants (TCAs) are a class of drugs that have approval from the U.S. Food and Drug Administration (FDA) to treat depression.
They work by increasing the levels of brain chemicals called neurotransmitters — specifically, serotonin and norepinephrine, which affect mood, attention, and pain.
In addition to depression, TCAs may be prescribed for obsessive-compulsive disorder (OCD), anxiety, insomnia, chronic pain, or migraine.
What Are Tricyclic Antidepressants?
TCAs are a class of antidepressants that alter the communication between nerve cells in the brain. They do this by increasing the amount of certain chemical messengers, or neurotransmitters.
Neurotransmitters regulate a range of bodily processes, such as mood, energy, and focus. It’s important to have an appropriate balance of neurotransmitters to sustain daily function.
If you have too much or too little of a certain neurotransmitter, such as serotonin, depression symptoms may develop. This is why boosting the levels of some neurotransmitters may help reduce mood disturbances in some individuals.
What Conditions Do Tricyclic Antidepressants Treat?
Although TCAs were the first class of antidepressants to be invented, most TCAs are no longer a first-line choice in treating depression. Nonetheless, they may still be used if other medications or treatments have not improved depression symptoms.
TCAs can also be used “off-label” to treat other conditions. This means it lacks FDA approval, but providers may still prescribe them based on research showing its effectiveness.
Depression
Depression is a mental health condition characterized by low mood and a loss of pleasure or interest in activities. Depression can also affect sleep, appetite, energy, and concentration.
Most TCAs have FDA approval to treat depression.
OCD
OCD is a mental illness involving intrusive thoughts (obsessions) and repetitive behaviors (compulsions) intended to reduce obsessions. OCD can disrupt healthy thinking patterns and interfere with daily functioning.
Clomipramine (Anafranil) has FDA approval for OCD treatment in people 10 years and older.
Anxiety Disorders
Anxiety refers to persistent and excessive worry, fear, or dread that’s disproportionate to a situation.
TCAs may be used off-label to treat anxiety disorders.
Migraine
Migraine is a complex and disabling neurological disease. Symptoms may vary, but a typical migraine attack may involve severe unilateral pain, sensory sensitivities, nausea, and vomiting.
Research has shown that some TCAs can prevent migraine attacks, despite its lack of FDA approval for migraine.
Amitriptyline (Elavil), doxepin (Sinequan), and nortriptyline (Aventyl, Pamelor) are the most common TCAs used in migraine prevention.
Chronic Pain
TCAs may also be used to treat chronic pain due to nerve-related (neuropathic) pain conditions. These may include diabetic neuropathy, postherpetic neuralgia, and myofascial pain.
Amitriptyline (Elavil) may be used to treat chronic pain.
Fibromyalgia
Fibromyalgia is a chronic widespread pain condition that can cause fatigue, memory issues, mood disturbances, and sleep difficulties.
TCAs may be used to treat fibromyalgia if first-line treatments don’t improve symptoms.
Insomnia
Insomnia refers to difficulty falling or staying asleep. Although TCAs don’t have FDA approval in treating insomnia, they may still be helpful.
Amitriptyline (Elavil) and doxepin (Sinequan) may be used to treat insomnia.
Bedwetting
TCAs may be prescribed to treat bedwetting in children 10 years and older if first-line therapies are ineffective.
Types of Tricyclic Antidepressants
Different TCAs may be used to treat different conditions.
Examples of TCAs include:
- Amitriptyline (Elavil)
- Amoxapine (Asendin)
- Clomipramine (Anafranil)
- Desipramine (Norpramin)
- Doxepin (Sinequan)
- Imipramine (Tofranil)
- Nortriptyline (Aventyl, Pamelor)
- Protriptyline (Vivactil)
- Trimipramine (Surmontil)
How Do Tricyclic Antidepressants Work?
TCAs work by increasing the amount of two mood-altering neurotransmitters: norepinephrine and serotonin.
Usually, neurotransmitters are absorbed back into the nerve cells that released them in a process called reuptake. This is how the body stops neurotransmitters from exerting their effects.
TCAs can block reuptake. This means neurotransmitters like serotonin and norepinephrine aren’t reabsorbed, and they can remain available for the brain to use. As a result, serotonin and norepinephrine’s effects on mood, attention, and pain may continue.
By blocking reuptake, TCAs may help improve mood and reduce pain signals.
What Are the Possible Side Effects of Tricyclic Antidepressants?
TCAs have a high risk of side effects, so physicians often start with a low dosage and gradually increase it based on a patient’s response.
Common side effects of TCAs may include:
- Drowsiness
- Blurry vision
- Constipation
- Dry mouth
- Low blood pressure when standing up from your seat, also known as orthostatic hypotension
- Urine retention (inability to completely empty the bladder)
Less common side effects may include:
- Unexpected or unintended weight loss
- Unexpected or unintended weight gain due to an increased appetite
- Increased sweating
- Shaking and tremors
- Low libido (sex drive)
- Erectile dysfunction
- Delayed orgasm
Certain TCAs may be more likely to cause specific side effects, such as drowsiness or weight gain, than others. Whether a patient experiences a particular side effect depends on their symptoms and any underlying health problems they may have.
TCAs aren’t addictive, but you may experience withdrawal symptoms if you suddenly stop or miss several doses. Withdrawal symptoms may include:
- Anxiety
- Agitation
- Chills, muscle aches, and other flu-like symptoms
- Drowsiness
- Headaches
- Irritability
- Nausea
- Sweating
It’s important to talk to your doctor about the best way to gradually and safely reduce your dosage.
Are There Any Risks Related to Tricyclic Antidepressants?
People taking TCAs, especially teenagers and young adults under 25, may be at increased risk for suicidal thoughts and behaviors. This risk is indicated in a black-box warning, which the FDA requires all antidepressants to have.
Some TCAs may also cause confusion in people 65 years and older, especially at higher dosages.
Certain medications can interact with TCAs. These include:
- Serotonin-norepinephrine reuptake inhibitors (SNRIs)
- SSRIs
- Anticholinergic drugs, including antihistamines or antipsychotics
- Anticoagulants (blood-thinning medications)
- Lithium (Eskalith)
- Clonidine (Catapres)
- Medications to treat blood pressure
- Cimetidine (Tagamet)
Doctors may avoid prescribing TCAs to people with certain health conditions to reduce the risk of complications. Let your doctor know if you have:
- Diabetes
- Heart problems
- A thyroid disorder
- An enlarged prostate
- Glaucoma
- Liver disease
- A history of seizures
- A family history of sudden death from heart problems or a heart condition called QTc interval prolongation
- A history of allergic reactions to TCA drugs
- Used monoamine oxidase inhibitors (MAOIs) within the past 14 days
TCAs also carry a higher risk of overdose than other antidepressants, so it’s important to take any TCA as directed by your doctor.
The Takeaway
Tricyclic antidepressants are a class of drugs that affect neurotransmitters, or chemical messengers, in the brain. They may be used to treat depression, migraine, chronic pain conditions, insomnia, and bedwetting in children. TCAs have an increased risk of suicidal thoughts, so be sure to talk to your doctor about the benefits and side effects before starting one.
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Angela D. Harper, MD
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Angela D. Harper, MD, is in private practice at Columbia Psychiatric Associates in South Carolina, where she provides evaluations, medication management, and psychotherapy for adul...
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Resources
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- Moraczewski J et al. Tricyclic Antidepressants. StatPearls. August 17, 2023.
- Sheffler ZM et al. Physiology, Neurotransmitters. StatPearls. May 1, 2023.
- Tricyclic Antidepressants and Tetracyclic Antidepressants. Mayo Clinic. March 30, 2022.
- Thour A et al. Amitriptyline. StatPearls. July 18, 2023.
- Almasi A et al. Doxepin. StatPearls. February 14, 2024.
- Spielmans GI et al. Duty to Warn: Antidepressant Black Box Suicidality Warning Is Empirically Justified. Frontiers in Psychiatry. February 13, 2020.