What are Antidepressants and How Do They Work?

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Antidepressants are amongst the most common classes of medications that doctors prescribe to treat mood disorders. Not only has the FDA approved antidepressants for treating depression, but some have their nod of approval for treating other conditions such as panic disorder, anxiety disorder, obsessive-compulsive disorder and premenstrual syndrome. What are antidepressants – and how do they work?

What Are Antidepressants?

Antidepressants have various modes of action, depending upon the type, but they all exert their action by altering levels of brain chemicals called neurotransmitters that affect mood. Most antidepressants alter levels of neurotransmitters such as serotonin, dopamine and norepinephrine. Lower levels of these neurotransmitters are associated with symptoms of depression, anxiety and other mood disorders.

Although antidepressants are commonly prescribed, they may not work significantly better than a placebo. That was the controversial finding of a study conducted by the Department of Psychology at Hull University in England and published in PLOS Medicine in February 2008. Researchers conducted a meta-analysis of clinical trials submitted to the FDA for the licensing of four new-generation antidepressants and found that the benefit “falls below accepted criteria for clinical significance.”

Types of Antidepressants

There are several different types of antidepressants with each affecting neurotransmitter levels in slightly different ways.

Tricyclic Antidepressants

Tricyclic antidepressants were widely used in the past, but they have fallen out of favor due to their side-effects and because of the development of a newer class of antidepressants called selective serotonin reuptake inhibitors. Tricyclic antidepressants alter levels of serotonin and norepinephrine in the brain. Unfortunately, they also cause unpleasant and sometimes serious side effects including heart palpitations, dry mouth, constipation, weight gain, lightheadedness, dizziness, tremors, sexual dysfunction, and blurred vision.

Selective Serotonin Reuptake Inhibitors

Since selective serotonin reuptake inhibitors entered the market, tricyclic antidepressants are used less often. Selective serotonin reuptake inhibitors or SSRIs work by elevating levels of the neurotransmitter serotonin in the brain. These medications are now widely prescribed, because they’re believed to be safer than tricyclic antidepressants. Still, they can cause low libido, dizziness, difficulty sleeping, dry mouth, weight gain and nervousness, which make it difficult for some people to tolerate them.

Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors or MAO inhibitors are another early type of antidepressants that are not widely used today because of their side-effects. They’re mainly used when a patient fails to respond to SSRIs or tricyclic antidepressants. These medications work by blocking the breakdown of serotonin, norepinephrine and dopamine, leading to higher levels of all three neurotransmitters in the brain.

Unfortunately, MAO inhibitors also prevent the breakdown of another protein called tyramine. When tyramine levels become too high, blood pressure elevates. Tyramine is found in some food and drink such as cheese, wine, soy and fava beans (to name a few), so people on MAO inhibitors shouldn’t eat these foods, as they will be unable to break down the tyramine in them.

Serotonin and Norepinephrine Reuptake Inhibitors

This is the most recent form of commonly prescribed antidepressants. Their side-effects are similar to the SSRIs, but they may have some advantages over them because they increase levels of both serotonin and norepinephrine, which may boost their effectiveness.

What are Antidepressants? The Bottom Line

Antidepressants have slightly different modes of action, but they all alter levels of neurotransmitters in the brain such as serotonin, norepinephrine and dopamine, although their effects on each individual neurotransmitter varies as do their side effects. Some people may tolerate one type of antidepressant better than another based on individual brain chemistry. Fortunately, there is a variety to choose from, but it may take some experimentation for an individual to find the one that is of most benefit with the least severe and lowest level of side-effects.


PLoS Med. 2008 Feb;5(2):e45.

Physician’s Desk Reference. 2010.