The 5 Major Classes of Antidepressants

MAOIs, SSRIs, SNRIs, TCIs, and Atypical

Prozac, Paxil and Zoloft anti-depressant tablets, close-up
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There are five major classes of antidepressants. Here's what they are, examples of each, and how they work.

Brain Chemicals Involved in Mood Regulation

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

  • Serotonin: 5-hydroxytryptamine (5-HT), more commonly known as serotonin, has been coined the brain's "feel-good" chemical.
  • Norepinephrine: Another neurotransmitter linked to depression and connected to how alert you feel. A low level of norepinephrine is thought to be associated with the brain fog that many people with depression experience.
  • Dopamine: You may have heard of low levels of dopamine in a part of the brain called the substantia nigra associated with Parkinson's disease, but there is much more to dopamine. In the frontal lobes of the brain, it's 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 that transmit messages throughout the brain. You may find it helpful to learn more about the role of neurotransmitters in depression.

Classes of Antidepressant Medications

Antidepressant medications are generally categorized based on how they affect these three molecules, although the tricyclics are an exception to this rule. The most common medications used at this time include the selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), though all of these medications have uses for some people.

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

Monoamine Oxidase Inhibitors

One of the first classes of antidepressants that were developed were 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 that are approved by the Food and Drug Administration (FDA) include:

  • Nardil (phenelzine)
  • Parnate (tranylcypromine)
  • Marplan (isocarboxazid)
  • Emsam (selegiline)

Monoamine oxidase inhibitors are used less often than other antidepressants and are somewhat difficult to take as they have many possibly life-threatening reactions when combined with other medications or foods containing tyramine. Taking MAOIs usually involves diet restrictions.

Tricyclic Antidepressants

Another early class of antidepressant is tricyclic antidepressants (TCIs), also known as tetracyclic or cyclic antidepressants, 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)
  • Asendin (amoxapine)
  • Anafranil (clomipramine)
  • Pamelor (nortriptyline)
  • Tofranil (imipramine)
  • Vivactil (protriptyline)
  • Surmontil (trimipramine)
  • Sinequan (doxepin)
  • Maprotiline

Tricyclic antidepressants, like MAOIs, 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 other conditions ranging from chronic pain to migraines to obsessive-compulsive disorder (OCD).

Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) work by inhibiting the reuptake of serotonin, allowing more serotonin to remain available. 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)
  • Lexapro (escitalopram)
  • Viibryd (vilazodone)

SSRIs tend to have fewer side effects than the older medications but can still 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 SSRIs except that they inhibit the reuptake of norepinephrine in addition to serotonin. The first SNRI was FDA-approved in December 1993.

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

Examples of SNRIs include:

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

Atypical Antidepressants

There are also other fairly new antidepressants which do not fit into any of the above categories, known as atypical antidepressants. Atypical antidepressants work by changing the levels of one or more neurotransmitters, such as dopamine, serotonin, or norepinephrine, but each one works in a different way. Some of these medications may be particularly helpful if you suffer from sexual side effects on other antidepressants.  

Examples of atypical antidepressants include:

  • Wellbutrin (bupropion)
  • Remeron (mirtazapine)
  • Desyrel (trazodone)
  • Trintellix (vortioxetine)
  • Nefazodone

Choosing the Best Antidepressant for Your Depression

There are several factors that go into choosing the best antidepressant. Part of your choice may come down to the side effects you would find most bothersome. Your doctor will help you decide which is the best medication for you, though you may have to try several before you find one that works the most effectively with the fewest side effects.

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 that may contribute to your depression such as chronic pain and self-help strategies. Take the time to learn coping tips for depression which can be helpful no matter what treatments you choose.

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