The Lowdown on Tricyclic Antidepressants (TCAs): How They Work and What They’re Used For

Author:

Jemma Strain

B.S. Psychology

Editor:

Emma Loker

B.S

When your mental or physical health becomes a burden that’s too heavy to bear, you may feel like you’ve exhausted every possible avenue to feeling better. Perhaps you’ve tried talking to someone, made healthy lifestyle changes, or even sought therapy.

If this is the case for you, the option of medication may have come up in conversation with a healthcare provider, possibly leading to the question “What are tricyclic antidepressants?”

Tricyclic antidepressants (TCAs) are medications originally designed to treat the symptoms of depression, but they’re also commonly used for a variety of other mental and physical issues. Yet TCAs come with a range of side effects that can affect how well many people tolerate them.

A mental health provider, like Mission Connection, can talk to you about whether TCAs are a good fit for you – and if there are any alternatives for your needs. This article also works as a helpful guide, covering…

What tricyclic antidepressants are
How TCAs work
Conditions tricyclics are used to treat
Potential tricyclic antidepressant side effects
How to stop TCAs safely
Answers to frequently asked questions about TCAs
Where to find professional mental health and medication guidance

What Are Tricyclic Antidepressants?

Tricyclic antidepressants (TCAs) are a family of medications designed to treat symptoms of major depressive disorder (MDD). While these medications were originally created to target depression, they’re now commonly also used for easing physical pain and improving peoples’ sleep patterns.¹

The origins of TCAs can be traced back to the late 1950s, with the introduction of the first Food and Drug Administration (FDA) approved tricyclic medication: imipramine (Tofranil).² This makes tricyclics one of the earliest medications designed to treat depression. However, while they still work for treating depressive symptoms, they’ve been pushed down the list of treatment options for a reason – their risk of side effects.

Because of their high risk of side effects, are TCAs still used today? In short, yes. But healthcare providers typically look towards the generally better-tolerated antidepressants as first-line treatments. These include selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).

Yet, everybody’s physical makeup is different, as are their mental health needs. So, if someone doesn’t respond as desired to SSRIs or SNRIs, then tricyclics may become a viable option. Plus, as mentioned, tricyclics aren’t only prescribed for depression. A doctor may also prescribe them off-label to help…

Break the cycle of pain
Improve the sleep-wake cycle
Reduce physical symptoms of pain

Off-label prescribing is commonplace, and simply means that a medication is being given for a condition it wasn’t originally designed for. However, a provider will always make the decision to prescribe tricyclics with care and consideration of your needs.

How Do TCAs Work?

Tricyclic antidepressants are first-generation antidepressants, and their name comes from the three rings that make up their structure and how they work. Like second-generation antidepressants (SSRIs and SNRIs), TCAs target the levels of chemicals in the brain, such as serotonin and norepinephrine. By altering the availability of these chemicals, tricyclics allow the brain to more effectively deliver signals to nerve cells, improving mood, focus, and overall outlook.

However, unlike second-generation antidepressants, tricyclics typically target norepinephrine more than the “happy hormone,” serotonin. TCAs also work differently by stimulating a range of other receptors in the brain. It’s these differences between first and second-generation antidepressants that make tricyclics less tolerated by a wider range of people. For instance, the additional chemicals they target can lead to dizziness, memory issues, and drowsiness, among other issues.²

Based on how tricyclics often lead to more side effects, they’re not the go-to medications for treating mental health issues such as anxiety and depression. But they still have an important place in healthcare, such as when other medications haven’t worked or in the treatment of sleep problems and chronic pain.

There is a wide range of tricyclic antidepressants, which are often prescribed for different purposes. Let’s briefly consider the TCA medications list before moving on to the conditions they’re commonly used to treat.

TCA Medications List:

Imipramine (Tofranil)
Amitriptyline (Elavil)
Amoxapine (Asendin)
Nortriptyline (Pamelor)
Trimipramine (Surmontil)
Protriptyline (Vivactil)
Doxepin (Silenor)
Desipramine (Norpramin)
Clomipramine (Anafranil)

With such an extensive list of medications, trying to determine whether one tricyclic is more suitable for your needs might feel like trying to pinpoint a drop in the ocean. However, each one works slightly differently from the other, so a provider can talk to you about your symptoms and needs to help you come to the right choice for you. The following sections may also help.

Uses of Tricyclic Antidepressants

The FDA has approved a variety of tricyclics for treating depression, including imipramine, amitriptyline, and nortriptyline, among others. However, the FDA has also approved certain tricyclics for other conditions. For instance, clomipramine is sometimes used to treat the symptoms of obsessive-compulsive disorder (OCD). Additionally, imipramine is FDA-approved for panic disorder and depression-related anxiety.

As mentioned, tricyclics are also prescribed off-label for issues such as pain-related conditions and sleep problems. The following sections explore how tricyclics can be used for conditions other than depression.

TCA Medications for Anxiety

Anxiety disorders can cause persistent and overwhelming fears about the past, present, and future, which can interfere with daily life. While imipramine is FDA-approved for panic disorders and clomipramine is approved for OCD, other tricyclics are sometimes used off-label for anxiety-related issues.

A provider may decide to treat anxiety with tricyclics if the second-generation antidepressants have not proven to be effective. However, the risk of side effects with tricyclics is higher, so they’re not considered to be a first-line defence. For this reason, tricyclic dosage for anxiety tends to be raised slowly to ensure the minimum amount needed for seeing benefits is used.³

TCAs for Chronic Pain

Chronic pain lasts from three months to several years, and can cause severe discomfort, which affects quality of life and satisfaction. TCAs have a strong evidence base for reducing the symptoms of chronic pain, as they can inhibit the pain receptors in the brain. However, due to their side effects, tricyclic antidepressants often only produce a moderate rate of satisfaction when used as pain relief. Therefore, their effects are monitored closely by a provider when used for chronic pain, as their cons sometimes outweigh their pros.⁴

TCAs for Fibromyalgia

Fibromyalgia is a condition that creates widespread and debilitating pain, yet the cause is unknown, and its risk factors are poorly understood. TCAs for fibromyalgia have been shown to be effective in reducing pain symptoms, yet it’s side effects cause problems for many people. Due to this issue, researchers explored the benefits of SSRIs in treating the symptoms of fibromyalgia, but with little success. However, SNRIs, such as duloxetine, may be a suitable alternative without the extensive side effects.⁵

Tricyclic Antidepressants for Migraines

Migraines are a neurological condition that cause intense headaches and often come with nausea and sensitivity to light and sound. In fact, in 2017, migraines were the seventh most widely reported cause of disability worldwide. Tricyclic antidepressants for migraines are an effective form of treatment as they inhibit pain receptors, but their success in treating this condition is similar to SSRIs and SNRIs. Therefore, due to the lower risk of side effects associated with these second-generation antidepressants, they may be a better choice of treatment for most people.⁶

Potential Tricyclic Antidepressant Side Effects

By this point, we’ve mentioned tricyclic antidepressant side effects a number of times. This is because the newer, second-generation antidepressants were developed specifically to provide an alternative to TCAs’ less-tolerated effects.

If a provider prescribes tricyclic antidepressants for your or a loved one’s symptoms, it’s because the better-tolerated alternatives have been exhausted or there are no other options. However, different tricyclics can have varying side effects. Plus, people often respond to the same medication uniquely. In other words, what might cause side effects in you might be well tolerated in someone else.

The following are common tricyclic antidepressant side effects. These often ease during the adjustment period, but if they persist, it’s worth checking in with your provider. They may talk to you about altering your dose or switching to another medication.

Tricyclic Antidepressant Side Effects:⁷

Dizziness
Constipation
Dry mouth
Blurred vision
Confusion
Difficulties urinating
Sedation
Increased appetite
Weight gain
Irregular heartbeat
Low blood pressure

Aside from these common side effects, there are a few severe side effects that must be considered with caution. Firstly, tricyclic antidepressants are linked to an increase in suicidal thoughts, especially in people under the age of 24.

Secondly, TCAs can contribute to heart issues and raise liver enzymes. Therefore, they’re not prescribed for people with a history of cardiac or liver problems. They can also increase the risk of seizures in people with epilepsy.⁷

Finally, there is a greater risk of tricyclic antidepressant overdose in comparison to other antidepressants. TCA overdose symptoms include dizziness, fainting, low blood pressure, irregular heartbeat, and seizures. TCA overdose can be fatal in extreme cases. If you notice any of these symptoms in yourself or someone else, it’s important to seek immediate medical assistance.⁸

For all of these reasons, the decision to prescribe tricyclic antidepressants is never taken lightly. A provider will assess medical history and current physical and mental well-being, as well as continue to monitor reactions to the medication throughout the course of treatment.

Stopping Tricyclics Safely: How to Taper off TCAs

There are many reasons why people might want to come off TCAs. For instance, they might feel like their symptoms no longer warrant medication, or find that the side effects of tricyclic antidepressants outweigh the benefits. If this is the case for you, you might be wondering how to stop taking TCAs.

Successfully stopping TCAs requires a slow and monitored approach. Suddenly stopping tricyclic antidepressants increases the risk of TCA withdrawal symptoms and the return of mental health symptoms. Yet tapering the dose over time under the guidance of a professional gives people the best chance at success and long-term recovery.

When stopping tricyclic antidepressants, it’s good to keep an eye out for TCA withdrawal symptoms. If you notice any of the following, make sure to communicate your concerns with your provider so they can manage any discomfort.

TCA Withdrawal Symptoms:⁹

Stomach upset
Restlessness
Irritability
Sleep disturbances
Anxiety
Flu-like symptoms
Headaches
Lethargy or drowsiness
Sensory issues, such as feelings of burning or tingling

Frequently Asked Questions About Tricyclic Antidepressants

This article aims to answer as many questions as possible about TCAs and their use in mental health and chronic pain conditions. Yet, as there is a long list of TCAs, their effects can vary – often leading to many questions and concerns. For this reason, we give answers to some FAQs about TCAs to help shed light on whether they’re the right fit for your needs.

Are TCAs Still Used Today?

Yes, tricyclic antidepressants are still used today, but, although they were created to treat depression, they’re currently more commonly prescribed for off-label conditions, such as chronic pain. When it comes to mental health conditions, second-generation antidepressants are often trialled first due to their lower risk of side effects. If these don’t work for your needs, your provider may talk to you about tricyclics.

Which Is the Right Antidepressant for Me? TCAs vs SSRIs

The right antidepressant for your needs will come down to your symptoms, age, weight, and so on. However, as discussed, SSRIs and SNRIs are normally the go-to for treating the majority of mental health conditions due to how well tolerated they are by many people.

Can TCAs Cause Weight Gain?

Yes, TCAs can cause weight gain. Amitriptyline and nortriptyline are the tricyclic antidepressants typically associated with the most weight gain in both short and long-term use.¹⁰ If weight gain is a concern for you, your provider can discuss alternatives to TCAs and help you create healthy nutrition and lifestyle plans.

Are Tricyclic Antidepressants Safe Long Term?

Recently, TCAs were shown to be beneficial in the short-term treatment of depression, but their long-term effects on quality of life remain relatively unknown.¹¹ This contradictory effect may come down to how long-term tricyclic antidepressant use may cause physical health concerns, particularly in older adults.

Mission Connection: Guiding You Through Meaningful Mental Health Treatment

When your life becomes troubled by mental or physical health concerns, returning to your status quo may become your main priority. You may long for the days when you felt hopeful, less anxious, slept better, or when physical pain wasn’t always burning during every movement.

Medication, such as tricyclic antidepressants, might seem like the solution to your problems – and for some people, perhaps it is. However, tricyclics aren’t a good fit for everyone due to their risk of side effects. So, what are the alternatives when you feel like your issues are a puzzle you can’t solve?

Mission Connection can help you put the pieces of the puzzle together. Our team of licensed professionals can guide you on the right choice of medication for your needs, as well as offer options for getting to the root of your issues. Medication works best alongside therapy for treating mental health issues, so we can ensure the best chance at long-term recovery by discussing the right evidence-based treatment package for you.

If you’re ready to talk or just want to ask more questions about medication, Mission Connection is always available. Contact us today to find out more.

References

Hull University Teaching Hospitals NHS Trust. (n.d.). Tricyclics anti-depressants for pain relief [Patient information leaflet]. https://www.hey.nhs.uk/patient-leaflet/tricylics-antidepressants-pain-relief/
Hillhouse, T. M., & Porter, J. H. (2015). A brief history of the development of antidepressant drugs: From monoamines to glutamate. Experimental and Clinical Psychopharmacology, 23(1), 1. https://doi.org/10.1037/a0038550
Bandelow, B., Michaelis, S., & Wedekind, D. (2017). Treatment of anxiety disorders. Dialogues in Clinical Neuroscience, 19(2), 93. https://doi.org/10.31887/DCNS.2017.19.2/bbandelow
Reinert, J. P., Veronin, M. A., & Medina, C. (2022). Tricyclic Antidepressants in Nociceptive and Neuropathic Pain: A Review of Their Analgesic Properties in Combination With Opioids. The Journal of Pharmacy Technology : JPT : Official Publication of the Association of Pharmacy Technicians, 39(1), 35. https://doi.org/10.1177/87551225221139699
Moret, C., & Briley, M. (2006). Antidepressants in the treatment of fibromyalgia. Neuropsychiatric Disease and Treatment, 2(4), 537. https://doi.org/10.2147/nedt.2006.2.4.537
Liu, Y. (2017). Tricyclic antidepressants for preventing migraine in adults. Medicine, 96(22), e6989. https://doi.org/10.1097/MD.0000000000006989
Moraczewski, J., & Aedma, K. K. (2023). Tricyclic antidepressants. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK557791/
BMJ Best Practice. (n.d.). Tricyclic antidepressant overdose. BMJ Publishing Group. https://bestpractice.bmj.com/topics/en-gb/342
Garner, E. M., Kelly, M. W., & Thompson, D. F. (1993). Tricyclic antidepressant withdrawal syndrome. Annals of Pharmacotherapy, 27(9), 1068–1072. https://doi.org/10.1177/106002809302700912
Gill, H., Gill, B., El-Halabi, S., Chen-Li, D., Lipsitz, O., Rosenblat, J. D., Van Rheenen, T. E., Rodrigues, N. B., Mansur, R. B., Majeed, A., W. Lui, L. M., Nasri, F., Lee, Y., & Mcintyre, R. S. (2020). Antidepressant Medications and Weight Change: A Narrative Review. Obesity, 28(11), 2064-2072. https://doi.org/10.1002/oby.22969
Kamp, C. B., Petersen, J. J., Faltermeier, P., Juul, S., Siddiqui, F., Barbateskovic, M., Kristensen, A. T., Moncrieff, J., Horowitz, M. A., Hengartner, M. P., Kirsch, I., Gluud, C., & Jakobsen, J. C. (2024). Beneficial and harmful effects of tricyclic antidepressants for adults with major depressive disorder: A systematic review with meta-analysis and trial sequential analysis. BMJ Mental Health, 27(1), e300730. https://doi.org/10.1136/bmjment-2023-300730