What Are the Major Classes of Antidepressants?

Antidepressant Classes - MAOIs, SSRIs, SNRIs and TCIs

Major Antidepressant Classes
What are the major classes of antidepressants and how do these differ?. Sergey Panteleev/Getty Images

What are the major classes of antidepressants, and how are these involved in the chemistry of depression?

Brain Chemicals Involved in Mood Regulation

There are three basic molecules, known chemically as monoamines, which are believed to be involved in mood regulation:

  • Serotonin - Serotonin or 5 hydroxytryptamine (5-HT) has been coined the brain's "feel-good" chemical.
  • Norepinephrine - Norepinphrine is another neurotransmitter linked with depression. It is often linked with alertness. A low level of norepinephrine is thought to be associated with the "brain-fog" that many people with depression note.
  • Dopamine - Dopamine has many diverse functions in the brain. You may have heard of low levels of dopamine in a part of the brain called the substantia nigra with Parkinson's disease, but there is much more to dopamine. In the frontal lobes of the brain it is linked with complex thinking and problem solving. In fact, it's thought that the stimulatory effects of chemicals such as nicotine and cocaine are related to their effects on the dopamine-mediated reward centers in the brain.

These molecules are neurotransmitters, chemical messengers which transmit messages throughout the brain. You may find it helpful to learn more about the role of neurotransmitters in depression (the biochemical basis of depression.)

Classes of Antidepressant Medications

Antidepressant medications are generally categorized based upon how they affect these three molecules, although the tricyclics are an exception to this rule.

The following are the major classes of antidepressants as well as their modes of action and examples of antidepressants belonging to those classes.

The most commonly medications used at this time include the selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, though all of these medications have uses for some people.

Monoamine Oxidase Inhibitors

One of the first classes of antidepressants that were developed were the monoamine oxidase inhibitors (MAOIs). This antidepressant type, which was discovered in the 1950s, inhibits the action of an enzyme called monoamine oxidase. Since monoamine oxidase's function is the breakdown of monoamines, its inhibition allows more of the neurotransmitters associated with mood regulation to remain available within the brain.

Examples of monoamine oxidase inhibitors include:

  • Nardil (phenelzine)
  • Manerix or Aurorix (moclobemide)

Monoamine oxidase inhibitors are used less often and somewhat difficult to take as they have many (and possibly life threatening) reactions when combined with other medications or foods containing tyramine.

Tricyclic Antidepressants

Another early class of antidepressant is the tricyclic antidepressants (TCIs) (also known as the heterocyclics), which were also discovered in the 1950s. Unlike the other classes of antidepressants, this class was named based upon its chemical structure, which is composed of three interconnected rings of atoms. Tricyclics exert their antidepressant effect by inhibiting nerve cells from reabsorbing serotonin and norepinephrine, which allows more of these substances to be available for use in the brain.

Examples of tricyclic antidepressants include

  • Elavil (amitryptyline)
  • Norpramin (desipramine)
  • Ascendin (amoxapine)
  • Anafranil (clomipramine)
  • Pamelor (nortryptyline)
  • Tofranil (imipramine)
  • Vivactil (protryptyline)
  • Surmontil (trimipramine)
  • Sinequan (doxepin)

Tricyclic antidepressants (like monoamine oxidase inhibitors) tend to have more side effects than the newer categories of antidepressants discussed below, including constipation, dry mouth, blurry vision, weight gain, and heart arrhythmias. They do, however, have some additional effects, and tricyclic antidepressants are used for many conditions ranging from chronic pain, to sleeping problems, to smoking cessation.

Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors (SSRIs) work by inhibiting the reuptake of serotonin, allowing more serotonin to remain available. The SSRIs were the first class of drugs that were intentionally developed as antidepressants rather than their antidepressant effects being discovered by chance. They were developed beginning in the 1970s.

Examples of SSRIs include:

  • Prozac (fluoxetine)
  • Paxil (paroxetine)
  • Zoloft (sertraline)
  • Celexa (citalopram)
  • Luvox (fluvoxamine)

SSRI's tend to have fewer side effects than the older medications, but can have adverse reactions, including sexual dysfunction. With the exception of Prozac, many of these medications should be weaned slowly when stopped as they may cause an uncomfortable constellation of symptoms referred to as SSRI discontinuation syndrome.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Serotonin and norepinephrine reuptake inhibitors (SNRIs) aid depression in a similar way to the SSRIs except that they inhibit the reuptake of norepinephrine in addition to serotonin. The first SNRI was FDA-approved in December 1993.

Increasing norepinehprine in addition to serotonin may be particularly helpful for people who notice fatigue with their depression (depression with psychomotor retardation). These medications are sometimes used for those with fibromyalgia and chronic fatigue syndrome as well.

Examples of SNRIs include:

  • Effexor (venlafaxine)
  • Cymbalta (duloxetine)
  • Pristiq (desvenlafaxine)
  • Savella (milnacipran)
  • Fetzima (leveomilnacipran)

Other Mechanisms of Action

There are also other fairly new antidepressants which do not fit into any of the above categories.  Some of these include:  Wellbutrin (buproprion), maprotiline, Remeron (mirtazapine, Vestra (reboxetine) Desyrel (trazodone), and Viibryd (vilazodone). Some of these medications may be particularly helpful for those who suffer sexual side effects on other antidepressants.

As more antidepressants are developed, these antidepressants may begin to develop into their own groupings of antidepressants or they may remain as standalone antidepressants.  For the time being, however, they remain unique in their modes of action.

Choosing the Best Antidepressant for Your Depression

There are several factors which go into choosing the best antidepressant. Part of your choice may come down to side effects which you would find most bothersome. Here are some questions to consider in making the choice.

It's also important to note that treating depression is usually most effective when a combination of modalities are used. These may include psychotherapy, carefully addressing any factors which may contribute to your depression, such as chronic pain, and self help strategies. Take the time to learn about these coping tips for depression which can be helpful not matter what treatments you choose


U.S. National Library of Medicine. Medline Plus. Antidepressants. Updated 02/15/17. https://medlineplus.gov/antidepressants.html

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