Tricyclic Antidepressants (TCAs): A Complete Guide

Tricyclic antidepressants, or TCAs, are a type of antidepressant. Developed in the middle of the 20th century, tricyclic antidepressants were some of the first prescription medications prescribed to treat depression and related conditions. 

Although tricyclic antidepressants were commonly used throughout the 20th century, they have largely been replaced by newer types of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors SNRIs.

Today, tricyclic antidepressants are still prescribed to millions of people every year in the United States. They’re often prescribed to treat depression when newer medications aren’t completely effective.

If you’ve been diagnosed with depression and haven’t experienced improvements after using an SSRI medication, your healthcare provider  may suggest a tricyclic antidepressant as an alternative. 

Below, we’ve listed the most common tricyclic antidepressants that remain in use today. We’ve explained how antidepressants of this type work, as well as the potential side effects you might experience if you’re prescribed a tricyclic antidepressant.

Finally, we’ve answered some of the most common questions about tricyclic antidepressants, from how long they take to work, to drug interactions, safety, stopping tricyclic antidepressants, withdrawal and more. 

Tricyclic Antidepressants (TCAs): An Overview

Tricyclic antidepressants were some of the first medications produced to treat major depressive disorder (MDD, or depression).

The first tricyclic antidepressants were developed in the 1950s. Imipramine, an early TCA, was developed in 1950s and approved in 1959 by the Food and Drug Administration (FDA). Amitriptyline, a TCA marketed under the brand name Elavil, was developed and approved in the ‘60s by the FDA

During the twentieth century, many healthcare professionals prescribed TCAs as a typical treatment for depression. Certain tricyclic antidepressants are currently prescribed or have been used in the past to treat:

• Anxiety disorders, such as generalized anxiety disorder (GAD), social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD)

• Post-traumatic stress disorder (PTSD)

• Eating disorders, such as bulimia nervosa

• Borderline personality disorder (BPD)

• Certain pain conditions, such as chronic pain and fibromyalgia

• Attention-deficit hyperactivity disorder (ADHD)

How Tricyclic Antidepressants (TCAs) Work

Tricyclic antidepressants work by increasing the concentration of serotonin, a neurotransmitter, in your brain. 

Serotonin, which is sometimes referred to as the “happiness chemical,” is one of a large variety of neurotransmitters that are used to transmit signals between neurons, or nerve cells. 

Neurotransmitters are used to control a diverse range of biological functions. Neurotransmitters help to manage your energy levels and alertness to your ability to fall and stay asleep, your sex drive, your appetite and more. 

Although serotonin is commonly associated with happiness, its real role in the body is far more complicated. For example, serotonin helps to regulate your mood and anxiety levels. It’s also a key neurotransmitter for regulating your digestive health, sleep patterns and bone health.

Research shows that depressed people often have low levels of serotonin transmission — a fact that’s a part of the “serotonin theory” of depression, which suggests that low levels of serotonin are a potential cause of depression.

Tricyclic antidepressants work by blocking the reuptake of the neurotransmitters serotonin and norepinephrine. This can increase the amounts of serotonin and norepinephrine present in the brain and produce an antidepressant effect.

List of Tricyclic Antidepressants (TCAs)

• Amitriptyline. Sold under the brand name Elavil®, amitriptyline is prescribed to treat depression. It’s also prescribed off-label for other health conditions, including irritable bowel syndrome.
  
  

• Amoxapine. Sold under the brand name Asendin®, amoxapine is prescribed to treat depression. It’s also prescribed for depression accompanied by anxiety or agitation.
  
  

• Desipramine. Sold under the brand names Norpramin® and Pertofrane®, desipramine is prescribed to treat depression. It’s also occasionally used off-label as a treatment for attention deficit hyperactivity disorder (ADHD).
  
  

• Doxepin. Sold under the brand names Sinequan® and others, doxepin is prescribed to treat depression and anxiety. It’s also used to treat certain depression and/or anxiety associated with diseases, alcoholism and some psychotic disorders.
  
  Doxepin is also marketed to treat sleeping disorders such as insomnia under several brand names, including Silenor®.
  
  

• Imipramine. Sold under the brand name Tofranil®, imipramine is prescribed to treat depression. It’s also used off-label to treat anxiety and panic disorder, and to treat bedwetting in children.
  
  

• Nortriptyline. Sold under the brand name Pamelor®, nortriptyline is prescribed to treat depression. It’s also used to treat attention deficit hyperactivity disorder (ADHD), some anxiety disorders, neuropathic pain and as a smoking cessation aid.
  
  

• Protriptyline. Sold under the brand name Vivactil®, protriptyline is prescribed to treat depression. It’s considered particularly suitable for patients who are withdrawn and/or apathetic.
  
  

• Trimipramine. Sold under the brand name Surmontil®, trimipramine is prescribed to treat depression. It’s also used to treat anxiety and, due to its sedative effects, some forms of insomnia.

Due to the significant side effects of these medications, most tricyclic antidepressants are no longer prescribed as first-line treatments for depression. 

Instead, your healthcare provider may prescribe one of the medications listed above in certain circumstances, such as:

• If you haven’t responded to newer antidepressants. Tricyclic antidepressants can often relieve depression when newer medications, such as SSRIs and SNRIs, are not effective.
  
  

• For conditions other than depression. Certain tricyclic antidepressants may be used off-label to treat conditions other than depression, such as pain syndromes, insomnia or psychiatric conditions such as obsessive-compulsive disorder (OCD) or panic disorder.

Using Tricyclic Antidepressants (TCAs)

Almost all tricyclic antidepressants come in tablet or capsule form. Depending on the specific medication and dosage you’re prescribed, you may need to take your tricyclic antidepressant one or several times per day.

Follow the instructions provided by your healthcare provider and use your medication only as prescribed.

Like other antidepressants, tricyclic antidepressants can take several weeks to start treating depression. It’s important to continue using your medication as prescribed during the first few weeks, even if you don’t notice any immediate improvements.

If you don’t notice any change in your mood, appetite, or energy levels after several weeks of starting a tricyclic antidepressant, talk to your healthcare provider. Do not make any changes to your medication usage or dosage without first consulting your healthcare provider.

Side Effects of Tricyclic Antidepressants (TCAs)

Compared to newer antidepressants, such as SSRIs and SNRIs, tricyclic antidepressants tend to cause more side effects. The side effects you may experience can vary based on the type of tricyclic antidepressant you’re prescribed, its dosage and other factors.

Some side effects caused by tricyclic antidepressants may become less severe or disappear on their own over time. However, others can be persistent. 

Common side effects of tricyclic antidepressants include:

• Blurred vision

• Confusion

• Constipation

• Dizziness

• Drowsiness

• Dry mouth

• Hyperhidrosis (excessive sweating)

• Sexual side effects, such as reduced sex drive, erectile dysfunction and difficulty or delay in reaching orgasm

• Sudden drops in blood pressure and lightheadedness when standing up after sitting down

• Urinary retention

• Weight gain and increased appetite

Of the tricyclic antidepressants, desipramine (Norpramin) and nortriptyline (Pamelor) may be less likely to cause significant side effects.

Some side effects, such as drowsiness and weight gain, may be more common with the medications amitriptyline (Elavil), doxepin (Sinequan), imipramine (Tofranil) and trimipramine (Surmontil).

If you develop persistent, severe or intolerable side effects after using a tricyclic antidepressant, talk to your healthcare provider. Your healthcare provider may suggest adjusting your dosage or switching to a more tolerable antidepressant.

Tricyclic Antidepressants (TCAs) Safety

Tricyclic antidepressants are generally safe if used as prescribed. However, there are certain side effects, drug interactions and other potential safety issues that you should be aware of if you’re prescribed a tricyclic antidepressant:

• Some tricyclic antidepressants may cause drowsiness. Doxepin, for example, is even marketed under the brand name Silenor as a medication for treating insomnia.
  
  If you’re prescribed a tricyclic antidepressant that can cause drowsiness, make sure to pay close attention to your response to the medication before driving a vehicle or doing any other activities that require alertness.

• Tricyclic antidepressants can cause drug interactions. Tricyclic antidepressants can interact with other prescription and over-the-counter medications, as well as some health supplements and natural products.
  
  Before you use any type of antidepressant, make sure that you inform your healthcare provider about all medications, supplements and health products that you currently use.

• Tricyclic antidepressants may worsen certain health conditions. If you have certain health conditions, using tricyclic antidepressants or other cyclic antidepressants may not be safe for you.
  
  If you have a heart condition, liver disease, glaucoma or a seizure condition, it is particularly important that you inform your healthcare provider before discussing any type of cyclic antidepressant.

• Although uncommon, certain tricyclic antidepressants may cause serotonin syndrome. A potentially dangerous condition, serotonin syndrome occurs when antidepressants lead to an unsafe level of serotonin in your body.
  
  Serotonin syndrome can occur when you use antidepressants at the same time as other medications that raise serotonin levels, such as other antidepressants or medications for migraine relief. Certain illicit drugs, such as cocaine, ecstasy, amphetamines and LSD, may also cause serotonin syndrome.

• Tricyclic antidepressants may not be safe to use if you’re currently pregnant. Tricyclic antidepressants are not considered safe in pregnancy and are linked to some congenital defects. Most tricyclic antidepressants are safe in breastfeeding, except Doxepin. It is important to discuss with your healthcare provider the medications you are taking when breastfeeding.
  
  If you’re currently prescribed a tricyclic antidepressant and believe that you could be pregnant, or plan to become pregnant in the near future, it’s important to talk to your healthcare provider.

• Antidepressants may increase suicide risk in teens and young adults. Like other antidepressants, tricyclic antidepressants carry a warning from the FDA notifying that they may increase the risk of suicide in people aged 24 and under.
  
  If you’re prescribed any type of antidepressant and are under the age of 24, make sure to stay alert and seek help from your healthcare provider if you experience any sudden changes in mood or develop suicidal thoughts.

• Suddenly stopping a tricyclic antidepressant may cause withdrawal symptoms. If you want to stop using your medication, it’s important that you talk with your healthcare provider before making any changes to avoid antidepressant withdrawal symptoms.

Other Medications for Treating Depression

Because of their side effect profile, tricyclic antidepressants are generally only prescribed if newer antidepressants are not effective. Before prescribing tricyclic antidepressants, your healthcare provider may recommend one of the following types of antidepressant:

• Selective serotonin reuptake inhibitor (SSRI). SSRIs are a typical first-line treatment for depression. They’re less likely to lead to side effects than older antidepressants and are generally well tolerated.

• Serotonin–norepinephrine reuptake inhibitor (SNRI). Another newer antidepressant class introduced in the 1990s, SNRIs are commonly prescribed to treat depression and certain chronic pain conditions.

• Dopamine reuptake inhibitor or norepinephrine–dopamine reuptake inhibitor (DRI or NDRI). These antidepressants target the neurotransmitter dopamine. Some DRIs and NDRIs may be less likely to cause sexual side effects than other antidepressants.

Frequently Asked Questions About Tricyclic Antidepressants (TCAs)

How Long Do Tricyclic Antidepressants Take to Work?

Although tricyclic antidepressants are generally effective at treating depression, it’s uncommon to notice an immediate improvement within a few days of using medication.

Typically, tricyclic antidepressants take several weeks to produce a noticeable improvement in your mood and general quality of life. It may take several weeks or longer before you begin to experience the full effects of any tricyclic antidepressant.

If you don’t notice improvements within a few weeks of starting an antidepressant, talk to your healthcare provider. Your healthcare provider may recommend adjusting your dosage or switching to a different type of medication. 

How Long Do You Need to Take Tricyclic Antidepressants?

It’s important to continue taking tricyclic antidepressants for as long as is recommended by your healthcare provider. 

Many people notice improvements after taking antidepressants for several weeks or months. It can be tempting to stop taking antidepressants after you notice improvements. However, doing this can increase your risk of experiencing side effects or depression relapse.

If you’re prescribed a tricyclic antidepressant and want to know how long you’ll need to continue using it, talk to your healthcare provider. Most clinicians recommend taking antidepressants for approximately six months after you feel better to prevent relapse.

What Are The Differences Between Tricyclic Antidepressants and SSRIs?

Although tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) are both used to treat depression, there are several differences between them:

• Both medications treat depression, but through different mechanisms of action. Tricyclic antidepressants act on approximately five neurotransmitter pathways to inhibit serotonin and norepinephrine reuptake.
  
  SSRIs target serotonin more specifically by blocking its reabsorption into neurons. Both types of medication increase serotonin levels and can help to treat depression.
  
  

• Tricyclic antidepressants are much older than SSRIs. The first tricyclic antidepressants were developed in the 1950s, whereas it wasn’t until the late 1980s that the first SSRIs came onto the market.
  
  

• Tricyclic antidepressants are more likely to cause certain side effects and interactions than SSRIs, SNRIs and other newer antidepressants.
  
  

• Tricyclic antidepressants generally aren’t used as a first-line treatment for depression, whereas SSRIs are. Instead, tricyclic antidepressants are often prescribed if SSRIs or other newer antidepressants aren’t effective.

Do Tricyclic Antidepressants Work for Anxiety?

Tricyclic antidepressants typically aren’t prescribed as first-line treatments for anxiety. However, some tricyclic antidepressants have been studied for use as anti-anxiety medications and may be prescribed off-label to treat certain anxiety disorders.

Can Tricyclic Antidepressants Cause Weight Gain?

Yes. Tricyclic antidepressants are commonly associated with weight gain. Several studies have noted that patients prescribed tricyclic antidepressants tend to gain small to moderate amounts of weight during treatment.

In a 1984 study, people prescribed low to modest doses of several tricyclic antidepressants had a mean monthly weight gain of 1.3 to 2.9 lbs and an average weight gain of three to 16 lbs over the course of treatment.

A study published in 2011 found that patients prescribed nortriptyline, a tricyclic antidepressant, gained an average of 2.64 lbs over 12 weeks -- more than those who were prescribed the SSRI escitalopram.

If you’re prescribed a tricyclic antidepressant and have recently gained weight, it’s important to talk to your healthcare provider before making any changes. Your healthcare provider may be able to recommend a different type of antidepressant that’s less likely to cause weight gain. 

Can You Overdose on Tricyclic Antidepressants?

Yes, you can overdose on tricyclic antidepressants. In fact, tricyclic antidepressant overdoses are some of the most common causes of drug poisoning seen in emergency departments.

Overdosing on tricyclic antidepressants can potentially be fatal. In small children, even one or two tablets of certain antidepressants can be dangerous. If you, your child or someone close to you has accidentally or intentionally taken an overdose of antidepressants, call 911 immediately. 

Is It Safe to Stop Taking Tricyclic Antidepressants?

If you’re prescribed a tricyclic antidepressant and want to stop taking it, it’s important to talk to your healthcare provider before doing so.

If you abruptly stop taking a tricyclic antidepressant, you may experience withdrawal symptoms — an issue referred to as antidepressant withdrawal. Symptoms of antidepressant withdrawal can include the following:

• Balance issues, such as feeling lightheaded, dizzy or lacking balance while walking

• Digestive issues, such as vomiting, nausea, diarrhea, cramps and a reduced appetite

• Difficulty sleeping, nightmares or other abnormal dreams

• Mood swings and feelings of anxiety, depression, irritability, confusion and agitation

• Facial flushing, excessive sweating or difficulty staying comfortable in hot weather

• Unusual sensations, such as numbness, tingling, pain and electric shock-like feelings that occur in your head

Stopping antidepressants too early may also cause your depression to develop again, affecting your recovery and setting back your progress.

If you no longer want to continue using tricyclic antidepressants, your healthcare provider will work with you to discontinue your medication safely. They may recommend that you gradually taper down your dosage over the course of several weeks or months.

You may also be prescribed a long-acting antidepressant to use while tapering to further lower your risk of developing withdrawal symptoms. 

Can You Drink Alcohol While Using Tricyclic Antidepressants?

Drinking alcohol while you’re using antidepressants, including tricyclic antidepressants, is not recommended. Alcohol and antidepressants can both cause drowsiness and make you less alert, increasing your risk of injury.

Alcohol can also contribute to depression and may worsen your symptoms or lead to suicidal thoughts and actions. The combined effects of alcohol and antidepressants may also increase strain on your liver.

If you’re prescribed any type of antidepressant, talk to your healthcare provider about the safety of drinking alcohol while taking your medication.