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How Do Antidepressants Work?


Updated May 15, 2014

Question: How Do Antidepressants Work?

Answer: Broadly speaking, all antidepressants fall into the following classes: monoamine oxidase inhibitors (MAOIs), tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs). There are also several newer medications that are unique in their mechanism of action.

The monoamine oxidase inhibitors (MAOIs) were some of the first antidepressant medications developed. The neurotransmitters responsible for mood, primarily norepinephrine and serotonin, are also known as monoamines. Monoamine oxidase is an enzyme which breaks these substances down. Monoamine oxidase inhibitors, as the name implies, inhibits this enzyme, thus allowing a greater supply of these chemicals to remain available.

Tricyclics, also known as heterocyclics, came into broad use in the 1950's. These drugs inhibit the nerve cell's ability to reuptake serotonin and norepinephrine, thus allowing a greater amount of these two substances to be available for use by nerve cells.

SSRI stands for Selective Serotonin Reuptake Inhibitor. These medications work, as the name implies, by blocking the presynaptic serotonin transporter receptor. This drug differs from the tricyclics in that it's action is specific to serotonin only. It's effect on norepinephrine is indirect, through the fact that falling serotonin "permits" norepinephrine to fall so preserving serotonin preserves norepinephrine.

Five newer medications which do not fit into the above categories are: buproprion (Wellbutrin), nefazodone (Serzone), trazodone (Desyrel), venlafaxine (Effexor), and mirtazapine (Remeron).


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