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What Are the Classes of Antidepressants?

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Insurance covers TMS for depression when a patient fails 4 different antidepressants from at least 2 different classes. (“Failing” a medication means that either depression symptoms didn’t improve, or that the patient couldn’t tolerate the side effects.) But what are antidepressant “classes?” 

Antidepressants work by increasing levels of chemicals in the brain called neurotransmitters. Antidepressants are sorted into “classes” based on which neurotransmitters they affect. 

It’s important that the patient try multiple classes, because while increasing one neurotransmitter may not work, increasing a different one might. The 5 classes of antidepressants are:

Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) work by increasing levels of serotonin (a neurotransmitter that regulates mood and behavior) in the brain. (1) Serotonin is often called the “happy chemical” because it is the main neurotransmitter responsible for feelings of well-being. Low levels of serotonin are linked to depression. (2) 

Serotonin is normally reabsorbed by the brain after it has been used. SSRIs block the absorption of serotonin in the brain to increase serotonin levels. 

SSRIs are one of the most commonly prescribed antidepressants because they are effective and have fewer side effects compared to other antidepressants.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Serotonin and norepinephrine reuptake inhibitors (SNRIs) work by increasing levels of serotonin and norepinephrine (two important neurotransmitters) in the brain. Typically, these neurotransmitters are reabsorbed by brain cells after they have been released and used. SNRIs prevent the reabsorption of serotonin and norepinephrine to increase levels of these neurotransmitters.

Your doctor may recommend SNRIs if you have chronic pain and/or symptoms of anxiety, in addition to depression.

Tricyclic Antidepressants (TCAs)

Tricyclic antidepressants work by increasing levels of both serotonin and norepinephrine (a neurotransmitter and hormone known to affect mood) in the brain (3) Just like SNRIs, TCAs work by blocking the reabsorption of serotonin and norepinephrine to increase levels of these neurotransmitters in the brain.

TCAs are just as effective as SSRIs, but are prescribed only after other antidepressants fail because they cause more serious side effects, like dizziness and confusion. (4)

Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs)

Noradrenergic and specific serotonergic antidepressants (NaSSAs) work by blocking receptors on brain cells that receive signals from monoamine neurotransmitters. Monoamine neurotransmitters include dopamine, norepinephrine, and serotonin. By blocking these receptors, NaSSAs increase levels of monoamine neurotransmitters to relieve depression symptoms. 

Researchers know that depression is linked with lower than normal levels of monoamines in the brain. (5) NaSSAs are as effective as SSRIs and TCAs but have fewer side effects. 

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors were the first class of antidepressants developed. (6) Monoamine oxidase is an enzyme that removes and breaks down the neurotransmitters norepinephrine, serotonin, and dopamine from the brain after they’ve done their job of helping brain cells communicate. MAOIs increase levels of these neurotransmitters by preventing monoamine oxidase from breaking them down. 

MAOIs are only used when other antidepressants don’t work because they can interact with certain foods, requiring patients to follow a strict diet, and can interact with other medications, including pain killers and other antidepressants.

Choosing the Right Depression Treatment

Your doctor will recommend an antidepressant based on your symptoms, the severity of your symptoms, and your health history. Sometimes, patients need to try more than one antidepressant before finding the right one. It can be frustrating when the first antidepressant doesn’t give you the results you want. But your doctor will work with you to find the treatment that gives you the best relief from depression. 

If antidepressants aren’t working, consider trying TMS, an FDA-approved and clinically-proven treatment for depression that’s covered by insurance. Learn more about TMS on our website, or take our quiz to learn whether you’re a candidate.


1. Selective serotonin reuptake inhibitors (SSRIs). The Mayo Clinic. Updated September 17, 2019. Accessed March 19, 2021.

2. Cowen PJ and Browning M. What has serotonin to do with depression? World Psychiatry. 2015;14(2):158-160. Accessed March 20, 2021.

3. Tricyclic antidepressants and tetracyclic antidepressants. The Mayo Clinic. Updated October 08, 2019. Accessed March 19, 2021.

4. Moraczewski J, Aedma KK. Tricyclic Antidepressants. StatPearls [Internet]. 2021. Updated Accessed March 21, 2021.

5. Elhwuegi AS. Central monoamines and their role in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(3):435-451. Accessed March 21, 2021.

6. López-Muñoz F, Alamo C. Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Curr Pharm Des. 2009;15(14):1563-1586. Accessed march 21, 2021.

Dr. Woo has been seeing patients in private practice since 2002, always with the goals of combining evidence-based medicine with psychodynamic psychotherapy and collaborating with other mental health professionals to ensure the best possible outcomes for his patients. He has been certified to administer TMS at his practice since 2017. His greatest clinical interests include helping patients suffering from depression, anxiety, and obsessive compulsive disorder.

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