Tricyclic antidepressants: Uses, common brands, and safety information

Depression, also known as major depressive disorder (MDD), affects almost 7 percent of adults in the U.S. in a given year—this translates to over 16 million people. Depression is the leading cause of disability in the U.S. in people ages 15 to 44 years old. 

Depression can cause symptoms that range from mild to severe and can affect your daily life, including sleep, eat, and work. To be diagnosed with depression, some of these mental health symptoms must be present for at least two weeks:

• Feeling sad, anxious, empty, hopeless, negative, irritable, restless, guilty, worthless, helpless

• Loss of pleasure

• Tiredness and low energy

• Talking and moving about more slowly

• Problems with concentration and memory

• Sleep disturbances, such as insomnia or sleeping too much

• Appetite/weight changes

• Pain without a physical cause

• Suicidal thoughts/behavior

Many people have a comprehensive treatment plan to treat depression, which may include counseling and medication. Antidepressant drugs are commonly prescribed (by a psychiatrist or primary care physician) to treat depression. 

Tricyclic antidepressants are a class of prescription drugs approved by the FDA (United States Food and Drug Administration) and are used to treat symptoms of depression. Continue reading to learn all about tricyclic antidepressants or TCAs.

Tricyclic antidepressants are a class of prescription drugs approved by the FDA (United States Food and Drug Administration) and are used to treat symptoms of depression. Continue reading to learn all about tricyclic antidepressants, or TCAs.

What are tricyclic antidepressants?

There are various types of antidepressants, including SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, SNRIs (serotonin-norepinephrine reuptake inhibitors), TCAs (described in this article), atypical antidepressants, and MAOIs (monoamine oxidase inhibitors). 

Tricyclic antidepressants (TCAs) were first introduced in 1959 to treat depression. TCAs are as effective as the more popular SSRIs, but TCAs cause more side effects and have a lower threshold for overdose and toxicity. Therefore, TCAs are not typically chosen as a first-line treatment for depression. However, they are still used to treat depression in many cases, and other conditions outlined below. 

How do tricyclic antidepressants work?

TCAs act on various neurotransmitters to help depression symptoms. They block serotonin and norepinephrine reuptake, which helps to elevate the mood. TCAs also act on various receptors, including cholinergic, muscarinic, and histaminergic receptors. The interactions with these receptors contribute to the side effects of TCAs. 

While not a first-line treatment of depression due to their many side effects, TCAs can still be an effective treatment for certain patients with depression or other conditions.

What are tricyclic antidepressants used for?

Tricyclic antidepressants are used for depression (major depressive disorder, or MDD). Different TCAs can be used for various indications, and your doctor can go into more detail about the different uses for particular TCAs. 

TCAs are sometimes used off-label for other reasons, such as:

• Migraine prevention

• Chronic pain

• Neuropathic pain or nerve pain (diabetic neuropathy, postherpetic neuralgia)

• Panic disorder/anxiety disorder

• Bipolar disorder

• Insomnia 

• Fibromyalgia

Also, imipramine is indicated to treat bedwetting in children ages six years and older. Clomipramine is indicated to treat OCD, or obsessive-compulsive disorder.

Types of tricyclic antidepressants 

Although TCAs are a class of antidepressants, they can be further categorized based on their structures, actions, and side effects. TCAs increase levels of serotonin and norepinephrine.  They also act as antagonists on alpha cholinergic, muscarinic, and histaminergic receptors. 

A TCA has a three-ring (tricyclic) structure, with an attached secondary or tertiary amine.

Secondary amines

Secondary amines have more of an effect on norepinephrine. These include desipramine, nortriptyline, and protriptyline.

Tertiary amines

Tertiary amines have more of an effect on serotonin. These include amitriptyline, clomipramine, doxepin, imipramine, and trimipramine.

Who can take tricyclic antidepressants?

Can men take tricyclic antidepressants?

Adult men can take TCAs, provided that they do not fall into one of the excluded categories below or take a medication that can interact with a TCA. 

Can women take tricyclic antidepressants?

Adult women can take TCAs, provided that they do not fall into one of the excluded categories below or take a medication that can interact with a TCA. However, TCAs can cause congenital defects, so women who are pregnant or planning to become pregnant should consult their healthcare provider regarding depression symptoms and medical advice.

Can children take tricyclic antidepressants?

TCAs are rarely used in children and teenagers because they are not as effective as other options, such as SSRIs. TCAs also have more side effects than SSRIs and other antidepressants. 

A TCA may be an option for treating depression in this age group if other alternatives have not worked. However, only the healthcare provider can determine if a TCA would be safe, considering the patient’s medical history, symptoms, and other medications the patient is taking that could interact with a TCA. 

Can seniors take tricyclic antidepressants?

TCAs have many side effects that can potentially be troublesome. Older adults are especially susceptible to these side effects. Also, older adults are likely to take more medications that can interact with TCAs. 

The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults states that older adults should avoid tricyclic antidepressants due to the side effects, including confusion, dry mouth, constipation, sedation, and possible toxicity. Also, orthostatic hypotension (low blood pressure when standing up, which can increase the risk of fainting and falls) is a risk. 

Are tricyclic antidepressants safe?

Tricyclic antidepressants recalls

There are no recalls for TCAs. 

Tricyclic antidepressants restrictions

Do not take a tricyclic antidepressant if you:

• Have certain heart problems or a family history of heart problems, such as QT prolongation or sudden cardiac death 

• Have had a hypersensitivity reaction to a TCA drug

• Take an SSRI, SNRI, or MAOI (monoamine oxidase inhibitor) antidepressant—use of a TCA and MAOI must be separated by at least 14 days. The combination of one of these drugs and a TCA can increase the risk of serotonin syndrome. Other drugs also interact with TCAs and increase the risk of serotonin syndrome, so review your medications thoroughly with your doctor. 

• Have angle-closure glaucoma

• Have a history of seizures

• Have difficulty urinating

• Have liver problems

Do not drink alcohol when taking a TCA. The combination of a TCA and alcohol can worsen the side effects of each and cause additive effects. These effects can include respiratory depression (breathing can slow or stop) and central nervous system (CNS) depression which can cause dizziness, drowsiness, and impairment. 

All antidepressants, including TCAs, have a black box warning, which is the strongest warning required by the FDA. Antidepressants may cause an increased risk of suicidal thoughts and behavior. Although this is more likely to occur in children, teenagers, and young adults, all people who take antidepressants should be closely monitored for changes in behavior and suicidal thoughts or behavior. 

Because TCAs are not compatible with certain medical conditions or medications, be sure to communicate with your doctor. Tell your doctor about all of the medical conditions you have and all of the drugs you take so that they can screen for drug interactions. Be sure to include all prescription and over-the-counter medicines, including vitamins and dietary supplements. 

Can you take tricyclic antidepressants while pregnant or breastfeeding?

TCAs are not safe during pregnancy. They may cause harm to the unborn baby in the form of eye, ear, face, and neck defects. Clomipramine has also been associated with heart defects. Consult your healthcare professional for medical advice regarding TCAs and breastfeeding.

Are tricyclic antidepressants controlled substances?

No, tricyclic antidepressants are not controlled substances.

Common tricyclic antidepressants side effects

TCAs are not the first choice for depression treatment because they cause troublesome side effects. While side effects vary by medication and by the individual, some of the most common side effects of tricyclic antidepressants include:

• Dizziness 

• Sedation 

• Constipation 

• Dry mouth 

• Blurred vision 

• Confusion 

• Urinary retention 

• Fast heart rate

• Low blood pressure when standing up from a sitting or lying position (orthostatic hypotension)

• Appetite increase and weight gain

Because TCAs can cause heart problems, your doctor will check your heart before prescribing a TCA. TCAs can cause heart rhythm abnormalities such as

• QT prolongation

• VFib

• Sudden cardiac death (in patients with preexisting heart disease)

Allergic reactions to TCAs are rare. If you experience symptoms of an allergic reaction such as hives, difficulty breathing, or swelling of the face, lips, or tongue, get emergency medical help right away. 

This is not a complete list of side effects. Other side effects may occur. Talk with your doctor about what side effects to expect from TCA treatment.

How much do tricyclic antidepressants cost?

Tricyclic antidepressants are very affordable, especially since they are available in generic form. Most insurances cover TCAs in the generic form. You can use a free SingleCare card to save up to 80 percent on tricyclic antidepressant prescriptions, and other prescription medications and refills, at participating pharmacies.