Tricyclic Antidepressants: How They Work, Uses, and Side Effects

Major depressive disorder, commonly known as depression, is among the most prevalent mental health conditions. While often mistaken for low mood or sadness, it is characterized by extreme feelings of sadness, emptiness, worthlessness, and hopelessness. It is also a prevalent condition, with nearly 21 million Americans being diagnosed with major depressive disorder every year. If ignored, it can be a very dangerous condition and in extreme cases, depression can lead to suicidal thoughts and actions.

The good news is that depression can be treated. Tricyclic antidepressants are the earliest kind of antidepressants developed to treat depression. While effective, they have been replaced by other medications given their harmful side effects. In this blog, we shall seek to understand what tricyclic antidepressants are, how they work, their uses, and their side effects.

What Are Tricyclic Antidepressants?

Tricyclic antidepressants, commonly abbreviated as TCAs, are first-generation antidepressants. They are known as tricyclic because of their chemical structure consisting of three rings. TCA drugs are the earliest type of antidepressants created to treat and manage major depressive disorder or clinical depression. They are, however, only one of the classes of antidepressants. There are others that came after and are generally more prescribed than TCAs given their efficacy and fewer side effects.

Today, TCAs are often prescribed for non-U.S. Food and Drugs Administration (FDA)-approved uses rather than for depression itself.

How Do Tricyclic Antidepressants Work?

Tricyclic antidepressants work by targeting neurotransmitters. Neurotransmitters are chemicals that are responsible for transmitting messages between one nerve cell and another in the brain. TCAs mainly target those neurotransmitters that are responsible for affecting mood. In doing so, they modify the brain chemistry and communication between the nerve cells to improve the symptoms of depression.

Now, serotonin and norepinephrine are two neurotransmitters in the brain that are often referred to as the “feel good” hormones. Both of these neurotransmitters regulate mood. TCAs block their reuptake, and in doing so, increase the levels of serotonin and norepinephrine in the brain, thereby elevating mood and improving other symptoms associated with depression.

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Common Uses of Tricyclic Antidepressants

Tricyclic antidepressants are FDA-approved medication for treating major depressive disorder or clinical depression. They are first-generation or the earliest created antidepressants. However, many other antidepressants that came after have fewer side effects than these TCA drugs and are more preferred in the treatment of depression. Therefore, TCAs have other off-label or non-FDA approved uses as well, which are as follows:

• Anxiety disorders
• Bedwetting behaviors
• Sleep difficulties like insomnia
• Migraine
• Chronic pain
• Fibromyalgia, a chronic condition that is characterized by pain, tenderness, and fatigue

List of Common Tricyclic Antidepressants

The FDA-approved list of tricyclic antidepressants are as follows:

• Amitriptyline
• Clomipramine
• Desipramine
• Doxepin
• Imipramine
• Nortriptyline
• Protriptyline

Please note that some of these TCA drugs are used in the treatment of other conditions other than depression. For instance, Clomipramine has been approved by the FDA in the treatment of obsessive-compulsive disorder. Imipramine, meanwhile, is used to treat bedwetting behaviors among children.

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Side Effects of Tricyclic Antidepressants

Coming to the side effects of tricyclic antidepressants, the main reason why they have not been preferred in the treatment of depression of lately. Some of the common tricyclic antidepressants’ side effects are as follows:

• Blurred vision
• Dry mouth
• Drowsiness
• Low blood pressure
• Dizziness
• Constipation
• Urinary retention or problems in passing urine

Some of the lesser known tricyclic antidepressants’ side effects are as follows:

• Increased appetite
• Weight gain/loss
• Severe sweating bouts
• Tremors
• Sexual problems, like low sex drive and erectile dysfunction

Along with tricyclic antidepressants’ side effects, there are certain risks and complications that need to be addressed as well.

If a person is pregnant or considering pregnancy, then the healthcare providers generally do not prescribe TCAs for depression or other conditions as they can lead to some safety issues during pregnancy. Prenatal exposure to TCAs can lead to birth defects and adversely impact the fetus’s ears, eyes, face, and neck.

In case of heart conditions, TCAs can lead to further complications especially among those suffering from ischemic heart disease. So, the healthcare providers assess the cardiac risk that TCAs can carry using electrocardiogram or EKG before starting treatment.

In case of epilepsy, TCAs are not generally prescribed by healthcare providers as they can increase the risk of seizures.

Therefore, it is very necessary to be very clear with the doctor regarding any pre-existing conditions if considering tricyclic antidepressant-based treatment.

Comparing Tricyclic Antidepressants vs. SSRIs

Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) are medications used in the treatment of depression. While TCAs are first-generation antidepressants, SSRIs are second-generation antidepressants as they came after TCAs. They are both FDA-approved for the treatment of depression and are effective as well. Their functioning is also similar in that they work by increasing serotonin levels in the brain.

However, TCAs lead to more side effects. In fact, they can also lead to toxicity and overdose. However, SSRIs are preferred by healthcare providers over TCAs in the treatment of depression as they carry fewer risks and side effects. Some of the SSRIs approved by the FDA in the treatment of depression are as follows:

• Citalopram
• Escitalopram
• Fluoxetine
• Paroxetine

Tricyclic Antidepressant Withdrawal

Tricyclic antidepressant withdrawal may sound confusing at the start, as TCAs are not known to be habit-forming drugs. However, if they are stopped abruptly or in case of missed doses, then one can still experience withdrawal symptoms. It is also called as the discontinuation syndrome, and the symptoms are as follows:

• Anxiety
• Irritability
• Restlessness
• Tingling and/or burning sensations
• Sleep difficulties
• Tiredness
• Headache
• Lightheadedness

Care must be taken to not stop or miss any of the TCA doses. They must be taken as prescribed by the doctor and any adjustments must be discussed with the doctor first.

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Are Tricyclic Antidepressants Still Used?

Yes, tricyclic antidepressants are still used. They are among the earliest antidepressants and have been quite effective. They are still very effective. However, given their many severe side effects, they are often not preferred by healthcare providers. They have been replaced by second-generation and even third-generation antidepressants. However, they can still be used to treat depression when other treatment options have failed.

In fact, even more so than depression, tricyclic antidepressants have off-label uses these days in the treatment of anxiety disorders, bedwetting, chronic pain, fibromyalgia, migraines, and so on.