By Dr. David Woo - May 8, 2023

Antidepressants are a type of medicine to treat depression or prevent it from reoccurring, as well as help treat other conditions by affecting neurotransmitters – chemicals in the brain – in the brain. Antidepressants are sorted into “classes” based on which neurotransmitters they affect.
Drugs used to treat depression include the following 5 classes: 

• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
• Tricyclic Antidepressants (TCAs)
• Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs)
• Monoamine Oxidase Inhibitors (MAOIs)

These drugs are thought to work by increasing neurotransmitters, like serotonin and noradrenaline, and aim to balance the brain’s chemistry. 
Given the chemical imbalance that causes depression varies, each class of antidepressants aims to affect different neurotransmitters:

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.

How to Find the Right Antidepressant for You?

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. 

It’s important that you try multiple classes of antidepressants because while increasing one neurotransmitter may not work, raising a different one, or a drug combination, might.

What to Do if Antidepressants Don’t Work?

If your depression symptoms return for more than a few days, you should see your doctor to assess your options and design a new treatment plan. 

If antidepressant-based treatments aren’t working, like in the case of treatment-resistant depression, or the drug’s side effects are worse than the results, consider trying TMS, an FDA-approved, psychiatrist-administered, and clinically-proven treatment for depression that’s covered by insurance.(7) Learn more about TMS on our website, or take our quiz to learn whether you’re a candidate.

Resources:

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

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

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

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

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

7. Zachary M. Sheffler, Preeti Patel, Sara Abdijadid. Antidepressants. StatPearls [Internet]. 2023. Link. Accessed May 1, 2023.

Dr. David Woo

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.