Antidepressants: What Are They, How Do They Work?


At its simplest, antidepressants are medications which are used to treat depression.  Chemically, they are drugs which are capable of altering the amount of the substances within your brain that scientists believe are responsible for regulating mood (neurotransmitters).

The Role of Neurotransmitters in Depression

To understand how antidepressants affect our brain’s chemistry, we must first take a look at what causes depression.  Although the causes of depression are not fully understood, scientists believe that that imbalances in substances in the brain called neurotransmitters are to blame.  Neurotransmitters function as chemical messengers within the brain, allowing messages to travel from one nerve cell to the next.  If these chemical messengers are not functioning properly, then it is thought that this may result in the symptoms that we know as depression.

There are three main neurotransmitters that are believed to be involved in depression:  serotonin, norepinephrine and dopamine.


Serotonin actually has many important function throughout the human entire body.  In addition to aiding in mood regulation and anxiety reduction, it plays roles in sleep, eating, digestion, wound healing, bone health and sexual desire.

Research indicates that decreased amounts of serotonin in the brain may be responsible for causing depression in many people, especially feelings of being suicidal.  In addition to being associated with depression, too little serotonin has been associated with obsessive-compulsive disorder, migraines, irritable bowel syndrome (IBS) and fibromylagia.  Low levels of serotonin have further been associated with many of the hallmark symptoms of depression, such as changes in appetite, anger and irritability,  cravings for carbohydrates and sleep difficulties.


Norepinephrine (also known as noradrenaline) also has important functions in the body.  It is an important factor in what is known as the fight-or-flight response, in which the body undergoes changes which allow it to better respond to environmental threats.  Norepinephrine increases the force of skeletal muscle contraction and the rate and force of the heart’s contractions.  These changes prepare the body to either fight a foe or to flee to safety.

Norepinephrine was targeted in the 1960’s as a likely cause of depression (the “catecholamine hypothesis.”)  The idea was that a deficiency in this important neurotransmitter leads to feelings of depression.  Current research on this link is mixed.  Certain people with depression do indeed have lower levels of norepinephrine, but not all people with decreased norepinephrine become depressed.  Some studies also seem to indicate that it is reduced levels of serotonin which actually lead to lower norepinephrine and subsequent depression.

Because norepinephrine’s job is to help the body recognize and prepare for dangerous, stressful situations, scientists feel that depression could be caused by the brain’s inability to mount an adequate response to stress.


Finally, the neurotransmitter dopamine has been linked to depression.  Dopamine’s function is in controlling the drive to seek out rewards and to feel pleasure.

Low dopamine could be the reason that people with depression experience decreased interest in and motivation to do things that used to bring them pleasure.

Other Neurotransmitters

While these three are the main neurotransmitters that have been associated with depression by researchers, there are certain neurotransmitters – such acetylcholine, glutamate, and Gamma-aminobutyric acid (GABA) – which are also thought to play a role in depressive disorders.  Further research will necessary to elucidate what role these other chemical substances may play.

How Antidepressants Affect Neurotransmitters

As stated above, antidepressants are medications which have the ability to influence the amount and availability of mood-regulating neurotransmitters in the brain.  The goal in making these alterations is to alleviate depression symptoms.

There are actually several different types, or classes, of antidepressants,  based primarily upon how they affect the neurotransmitters.

Reuptake Inhibitors

Some of the most common antidepressants are reuptake inhibitors.  What this means is that they prevent nerve cells from taking back up and breaking down neurotransmitters after they’ve done their job of transmitting their chemical message.  This allows more of the neurotransmitters to remain available for use, hopefully allowing the brain to do a better job in regulating mood.

Reuptake inhibitors fall into three main classes:  selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and norepinephrine and dopamine reuptake inhibitors (NDRIs).  As their various names indicate, these medications are capable of influencing the availability of neurotransmitters is a very targeted way.


SARIs (serotonin antagonist and reuptake inhibitors) exert their action in two probable ways.  Firstly, they appear to block the reuptake of serotonin.  In addition, they also seem to prevent serotonin from binding to certain undesirable receptors, instead directing them to receptor sites that are more desirable in mood regulation.


This older class of antidepressants derives its name from the chemical structure of its members rather than how they work.  They have a structure composed of three rings of atoms.

Tricyclics work by inhibiting the reuptake of serotonin and/or norephinephrine.


The tetracyclics are another older class of antidepressant.  Like the tricyclics,  their name is derived from their structure.  Antidepressants in this class have four rings of atoms rather than three.

Also like the tricyclics, they work by inhibiting the reuptake of serotonin and/or norepinephrine.


Monoamine oxidase inhibitors (MAOIs) are another older class of antidepressants which work a bit differently from the other classes.  MAOIs block the action of an enzyme called monoamine oxidase.  Monoamine oxidase breaks down serotonin, norepinephrine and dopamine.  When its action is blocked, this can increase the availability of these neurotransmitters, possibly alleviating depression.

Antidepressants Not Just for Treating Depression

While the name antidepressant might seem to imply that these drugs are only used to treat depression, they do have applications in treating many different conditions related to neurotransmitter imbalances.  Anxiety disorders, agitation, obsessive-compulsive disorder, manic depressive disorders, bedwetting, neuropathic pain and posttraumatic stress disorder are some of the many conditions which are approved for treatment with antidepressants.  In addition, many doctors also treat conditions such as fibromyalgia, chronic hives, hot flashes, drug-induced excessive sweating, itching, premenstrual syndrome, eating disorders and Tourette’s syndrome with antidepressants.

Nancy Schimelpfening, MS

Nancy Schimelpfening is the founder of Depression Sanctuary. Unless otherwise stated, all of the content on Depression Sanctuary is written by and maintained by Nancy. Nancy has a master’s degree in community health education from Old Dominion University in Norfolk, VA. She was the (now expert on depression from 1998-2016. She has also written for other online publications, including Healthline, Health Digest, and MindBodyGreen.