Which is an Example of a Tricyclic Antidepressant? A Comprehensive Guide

October 9, 2025 •

4 min read

In 2023, about 11.4% of adults in the U.S. took prescription medication for depression [1.3.4]. Amitriptyline is a well-known answer to the question, 'Which is an example of a tricyclic antidepressant?', representing an older but still relevant class of these medications [1.2.2].

Quick Summary

Amitriptyline is a primary example of a tricyclic antidepressant (TCA), an early class of drugs for depression [1.2.2]. TCAs work by increasing serotonin and norepinephrine levels in the brain to improve mood and are also used for pain and migraines [1.4.2, 1.5.2].

Key Points

Amitriptyline as a Prime Example: Amitriptyline is a well-known example of a tricyclic antidepressant (TCA), an early class of drugs for depression [1.2.2].
Dual Mechanism of Action: TCAs work by increasing the levels of both norepinephrine and serotonin in the brain, which helps regulate mood [1.4.2].
Versatile Treatment Options: Beyond depression, TCAs are frequently used off-label to treat chronic nerve pain, prevent migraines, and manage insomnia [1.5.1].
Second-Line Treatment Status: Due to a higher side effect burden and overdose risk, TCAs are typically considered a second-line treatment for depression after SSRIs have been tried [1.2.4].
Significant Side Effects: Common side effects include dry mouth, drowsiness, constipation, and blurred vision, stemming from their broad action on multiple neurotransmitter systems [1.8.4].
High Overdose Risk: TCA overdose is a serious medical emergency that can lead to life-threatening cardiac arrhythmias and seizures [1.9.1].
Important Medical Supervision Required: Patients must disclose their full medical history, including heart conditions, and all current medications to their doctor before starting a TCA to avoid dangerous interactions [1.10.2].

Understanding Tricyclic Antidepressants (TCAs)

Tricyclic antidepressants (TCAs) are a class of medications first introduced in the 1950s, making them one of the earliest types of antidepressants [1.4.1, 1.5.5]. Their name comes from their chemical structure, which contains three rings of atoms [1.4.1]. Although they have largely been succeeded by newer medications with fewer side effects, such as Selective Serotonin Reuptake Inhibitors (SSRIs), TCAs remain an important treatment option, especially when other medications are not effective [1.2.3].

A primary example of a tricyclic antidepressant is Amitriptyline (formerly sold as Elavil) [1.2.2]. Other common TCAs approved by the U.S. Food and Drug Administration (FDA) include:

Imipramine (Tofranil) [1.7.3]
Nortriptyline (Pamelor) [1.7.3]
Doxepin (Sinequan) [1.7.3]
Desipramine (Norpramin) [1.7.3]
Clomipramine (Anafranil) [1.2.2]

How Do TCAs Work?

The primary mechanism of action for TCAs involves blocking the reuptake of two key neurotransmitters in the brain: norepinephrine and serotonin [1.4.2]. By preventing these chemical messengers from being reabsorbed by nerve cells, their levels in the synapse (the gap between neurons) increase [1.4.1]. This elevated concentration helps improve communication between brain cells, which can alleviate symptoms of depression [1.4.2].

TCAs are categorized into two main groups based on their chemical structure:

Tertiary amines (e.g., amitriptyline, imipramine, doxepin) tend to inhibit serotonin reuptake more significantly [1.4.1].
Secondary amines (e.g., nortriptyline, desipramine) show a greater inhibition of norepinephrine uptake [1.4.1].

This broad action on multiple neurotransmitter systems is what makes TCAs effective, but it is also the reason for their extensive side effect profile, as they also block histamine, acetylcholine, and alpha-adrenergic receptors [1.8.3].

Beyond Depression: Other Uses for TCAs

While originally developed for major depressive disorder, TCAs are prescribed for a wide range of 'off-label' conditions, meaning uses not officially approved by the FDA but supported by clinical evidence [1.2.3].

Common off-label applications include:

Chronic Pain Syndromes: TCAs, particularly amitriptyline, are effective in managing neuropathic pain (nerve pain) from conditions like diabetic neuropathy, fibromyalgia, and postherpetic neuralgia [1.2.3, 1.5.1]. Their pain-relieving effects are believed to be independent of their mood-lifting effects [1.5.1].
Migraine Prevention: Amitriptyline, nortriptyline, and doxepin are among the most common TCAs used to prevent chronic migraines and tension headaches [1.2.3].
Insomnia: Due to their sedative properties, some TCAs like doxepin and amitriptyline are used at low doses to treat difficulty falling or staying asleep [1.2.3, 1.5.1].
Obsessive-Compulsive Disorder (OCD): Clomipramine (Anafranil) is specifically FDA-approved for treating OCD [1.2.1].
Childhood Bed-wetting (Enuresis): Imipramine has been used to treat bed-wetting in children [1.2.1].
Anxiety Disorders: TCAs can be effective for panic disorder and generalized anxiety, though they are typically not a first-line treatment [1.2.3].

Comparison of Antidepressant Classes: TCAs vs. SSRIs

TCAs are now considered a second-line treatment, with SSRIs being the more commonly prescribed first-line option [1.2.4]. This is primarily due to differences in their side effect profiles and safety in case of overdose [1.6.3].


Feature	Tricyclic Antidepressants (TCAs)	Selective Serotonin Reuptake Inhibitors (SSRIs)
Mechanism	Block reuptake of serotonin and norepinephrine; also affect other neurotransmitters [1.4.2].	Selectively block the reuptake of serotonin only [1.6.3].
Primary Example	Amitriptyline, Imipramine [1.2.2]	Fluoxetine (Prozac), Sertraline (Zoloft) [1.2.4]
Common Side Effects	Dry mouth, constipation, blurred vision, drowsiness, dizziness, weight gain [1.8.4].	Nausea, insomnia, agitation, sexual dysfunction [1.6.2].
Overdose Risk	High risk of severe toxicity, including potentially fatal cardiac arrhythmias and seizures [1.8.2, 1.11.3].	Lower risk of severe toxicity in overdose compared to TCAs [1.6.3].
Primary Use	Second-line for depression; first-line for some chronic pain conditions [1.2.4, 1.5.1].	First-line treatment for depression and anxiety disorders [1.2.4].

Important Safety Considerations and Side Effects

The decision to use a TCA must be carefully weighed by a healthcare provider, considering the patient's medical history and other medications.

Common side effects include:

Anticholinergic effects: Dry mouth, blurred vision, constipation, and difficulty urinating [1.8.4].
Cardiovascular effects: A drop in blood pressure upon standing (orthostatic hypotension), fast heart rate, and palpitations [1.8.4]. A baseline electrocardiogram (ECG) is often recommended, especially for older adults or those with heart conditions [1.9.2].
Cognitive effects: Drowsiness and confusion, particularly in older adults [1.8.4].
Other effects: Weight gain and sexual dysfunction are also possible [1.8.4].

Serious Risks:

Overdose: A TCA overdose is a medical emergency and can be fatal, primarily due to cardiac arrest and seizures [1.9.1]. Symptoms can appear rapidly and include confusion, irregular heartbeat, and coma [1.11.3].
Suicidal Thoughts: The FDA requires a boxed warning on all antidepressants, including TCAs, noting an increased risk of suicidal thinking and behavior in children, adolescents, and young adults under 25 [1.9.2].
Drug Interactions: TCAs can have dangerous interactions with many other drugs, including MAOIs, SSRIs, and even some over-the-counter medications. Combining them with other serotonergic drugs can lead to serotonin syndrome, a life-threatening condition [1.7.1, 1.9.3].

Conclusion

Amitriptyline and imipramine are classic examples of tricyclic antidepressants, a powerful but complex class of medications. While newer drugs like SSRIs are now preferred for treating depression due to their more favorable safety profile, TCAs remain a valuable tool in modern pharmacology [1.2.4, 1.6.3]. They are particularly useful for treating severe depression that has not responded to other therapies and have found a significant role in managing chronic pain, migraines, and insomnia [1.5.1]. Due to their significant side effects and overdose risk, their use requires careful medical supervision [1.9.1].

For more in-depth information, you can visit the National Library of Medicine's resource on Tricyclic Antidepressants: https://www.ncbi.nlm.nih.gov/books/NBK557791/

Frequently Asked Questions

Amitriptyline is one of the most common and widely recognized examples of a tricyclic antidepressant [1.2.2]. Other examples include imipramine and nortriptyline [1.2.1].

TCAs have more significant side effects and are much more dangerous in an overdose compared to newer antidepressants like SSRIs [1.6.3]. SSRIs have a more targeted mechanism of action, leading to a better safety profile, making them a first-line treatment choice [1.6.1].

Yes, TCAs are very effective for treating chronic neuropathic (nerve) pain, such as that from diabetes or fibromyalgia [1.5.1]. This pain-relieving effect can occur at lower doses than those used for depression [1.5.1].

The most common side effects are related to their anticholinergic properties and include dry mouth, drowsiness, constipation, blurred vision, dizziness, and weight gain [1.8.1, 1.8.4].

Yes, an overdose on a TCA is extremely dangerous and can be fatal. It can cause severe complications, including seizures, coma, and life-threatening cardiac arrhythmias [1.11.3]. This risk is a major reason they are prescribed with caution [1.9.1].

Tricyclic antidepressants work by blocking the reabsorption (reuptake) of the neurotransmitters serotonin and norepinephrine into brain cells. This increases the active levels of these chemicals in the brain, which helps to improve mood and regulate pain signals [1.4.2].

You should inform your doctor about all your medical conditions, especially any history of heart disease, seizures, glaucoma, or urinary retention [1.10.2]. Also, provide a complete list of all medications you take, including over-the-counter drugs and supplements, to avoid potentially dangerous drug interactions [1.10.4].