Tricyclic antidepressants (TCAs) are a class of medications prescribed for treatment-resistant depression. TCAs are an older class of antidepressants that are less commonly prescribed because they have a higher risk of adverse effects than newer SSRI antidepressants, and also carry a higher risk for overdose. [1][2]
- Tricyclic antidepressants are an older class of antidepressant medications that are used in treatment-resistant depression.
- Newer types of antidepressants have replaced TCAs as a frontline treatment because they have a superior safety profile and are less likely to cause serious adverse effects.
- TCAs may be recommended in cases of severe depression that has not responded to other treatments like SSRI medication.
What are tricyclic antidepressants?
Tricyclic antidepressants were first introduced in 1959 to help in the treatment of mental illnesses like depression. While they were once a frontline treatment option for major depressive disorder, they have largely been replaced by newer SSRI antidepressant medications as a preferred treatment. [1][2]
Tricyclic antidepressants are now considered a second-line treatment for depression that are introduced when first-line treatments are ineffective. TCAs are commonly used in addition to newer antidepressants for severe depression that does not respond to SSRIs or other newer antidepressants. [2]Â
How tricyclic antidepressants work
Tricyclic antidepressants work on certain mood-regulating neurotransmitters in the brain. Specifically, the antidepressant effects of TCAs are believed to be linked to their work on two key neurotransmitters: serotonin and norepinephrine. TCAs work by inhibiting these neurotransmitter sites to accumulate more of these neurochemicals, which helps to improve mood, concentration, and energy.[1]
What TCAs are used for today
While TCAs used to be a frontline treatment option for depression, they are less commonly prescribed today. Because of the safety risks and adverse effects linked to TCAs, most prescribers recommend using newer antidepressants like SSRIs for the treatment of depressive symptoms. TCAs are usually only recommended when other antidepressants have not been effective in reducing or managing symptoms. [1]
TCAs are also sometimes prescribed for off-label use in the treatment of: [1]
- Obsessive-compulsive disorder
- Migraines
- Nerve pain and fibromyalgia
- Diabetic neuropathy
- BedwettingÂ
Side effects of tricyclic antidepressants
Many people who take tricyclic antidepressants report side effects, which can range from mild to severe in nature. In some cases, side effects related to TCAs become so impairing that a person needs to discontinue their medication. In other instances, the side effects remain mild and are outweighed by the benefits of these medications. [1]
The risk for serious adverse effects is higher for tricyclic antidepressants than for other, newer antidepressants like SSRIs and MAIOs. Because of this, most prescribers do not recommend TCAs as a frontline treatment for depression. [2]
Common side effects
Some of the most common side effects of tricyclic antidepressants are relatively mild in nature. Many people describe TCA side effects like dry mouth, constipation, and urinary retention. It is also common for people to describe feeling sedated, confused, dizzy, and having blurred vision. Some also report dizziness upon standing, which may be a sign of changes in heart rate and blood pressure and should be discussed and evaluated by a medical professional. [1]
Increased appetite is also a common side effect of tricyclic antidepressants. In some instances, this can lead to significant weight gain. [1]
Serious risks
Some people who take TCAs experience more serious and severe side effects, which may require urgent medical or psychiatric care. One of the most serious side effects of TCAs is the risk for increased suicidal thoughts and behaviors, which is more common in young adults. [1]Â
In addition to suicidality, other serious risks of TCAs include: [1]
- Increased risk for heart problems, heart attacks, and strokes.
- Increased risk for seizures in individuals with epilepsy.
- Risk of birth defects in pregnant and breastfeeding women.
Tricyclic antidepressants and overdose risk
Unlike newer antidepressants, tricyclic antidepressants do carry a much higher risk for accidental or intentional overdose. People who overdose on TCAs can experience severe symptoms that affect their heart, brain, and nervous systems, and often require immediate medical attention. Often, TCA overdose will result in a rapid decline in cognition and vital signs, including tachycardia, hypotension, and an inability to communicate clearly. [1][3]
Without treatment, TCA overdose can be fatal, resulting in heart failure, seizures, and other life-threatening complications. Often, emergency treatments are needed to block further absorption of the medication and prevent long-term irreversible damage to organs in the body. [3]
Abuse and misuse potential of TCAs
Tricyclic antidepressants are not commonly misused, except in prisons and other institutionalized settings where access to other illicit drugs is more restricted. There have been some reports of misuse of TCAs in these settings, which is believed to be related to their sedating and mood-boosting effects. [4]
TCA abuse has also been reported by polydrug users, who may use these medications to potentiate the effects of other substances. While uncommon, tricyclic antidepressant misuse carries serious risks to health, including the risk of a fatal overdose. [3][4]
TCAs vs. Newer antidepressants
Tricyclic antidepressants have been around since 1959, and were once the preferred frontline treatment for depression. Since then, they have largely been replaced by newer types of antidepressants like SSRIs and MAOIs, which have shown to have a superior safety profile. [1][2]Â
Specifically, there is less risk for serious, long-term side effects with newer antidepressants, and research shows that this makes people more likely to continue their medication over time. Also, TCAs carry a higher risk for overdose than newer antidepressants, which is another reason they are less commonly prescribed. [3]
Because of these health considerations, TCAs are often only prescribed to people who have tried a newer antidepressant and have not experienced relief from their symptoms. Even in these instances, TCAs are often used in adjunct with newer antidepressants to target depressive symptoms. [1]
Who should be cautious with TCAs
There are some individuals who may be at higher risk for serious complications and adverse effects related to tricyclic antidepressants. Individuals with pre-existing renal, hepatic, or cardiac problems should consult with their doctors before starting TCAs, as these medications can have adverse effects on the liver, kidneys, and heart. Also, people who have epilepsy may experience an increase in seizures related to the use of tricyclic antidepressants. [1]
Women who are pregnant or trying to become pregnant are not advised to take tricyclic antidepressants due to the risk for fetal and developmental harm. Breastfeeding women are also cautioned against the use of TCAs, which can be transferred via breastmilk to their baby. Usually, TCAs are not prescribed to children and are cautiously prescribed to young adults, due to the risk for increased suicidal ideation and behavior. Geriatric patients may also be more prone to experience adverse effects due to changes in drug absorption and metabolism as we age. [1]
Safe use and monitoring
All medications carry some risk for side effects and complications, and should only be taken under the advice and care of a prescribing professional who is familiar with your health history. Disclosing any pre-existing conditions and use of other medications or illicit substances is also important to help prevent adverse effects related to drug interactions.Â
Before starting, stopping, or changing your dose of a medication, you should always consult closely with a medical professional. Monitoring and tracking any symptoms and side effects will prepare you to provide accurate information to your provider, who can make individualized recommendations based on this information.Â
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