What Are the Top 5 Antidepressants?

Medically Reviewed on 2/8/2022

Top 5 antidepressants to treat depression

The top 5 antidepressants to treat depression include SSRIs, SNRIs, atypical antidepressants, serotonin modulators, and cyclic antidepressants.

Antidepressants are prescription medicines used to treat depression. They are often used for treating other psychological disorders, such as anxiety disorders.

There are different types of antidepressants based on the way they work (mechanism of action), which include the following:

1. Selective serotonin reuptake inhibitors (SSRIs)

The most prescribed antidepressants by physicians are due to the low side effects experienced with these drugs.

SSRIs work by increasing the serotonin levels in the brain that are comparatively low during the depression. Serotonin is a hormone that stabilizes moods and causes feelings of well-being and happiness.

Other functions of serotonin include:

Once the serotonin exhibits its function, the nerve cells reabsorb (reuptake) the serotonin to terminate their action. When serotonin levels are low, reuptake can restrict the amount of serotonin being circulated actively in the brain. SSRIs prevent serotonin reuptake, thereby increasing the serotonin levels circulating in the brain.

Some of the commonly prescribed SSRIs include:

Common side effects observed with SSRIs include:

2. Serotonin and norepinephrine reuptake inhibitors (SNRIs)

They are often prescribed due to their superior efficacy and safety profile. SNRIs work by increasing serotonin and norepinephrine levels in the brain. Norepinephrine is a hormone and a neurotransmitter responsible for transmitting signals across nerve endings.

Some of the functions of norepinephrine in the brain include:

  • Regulating sleep and wake cycle
  • Increasing attention
  • Memory storage
  • Improving focus while performing a task
  • Improves alertness and energy

Norepinephrine and serotonin are responsible for preventing depression symptoms. SNRIs prevent the reuptake of serotonin and norepinephrine by the nerve cells, thus increasing their level in the brain.

Some of the common SNRIs include:

Common side effects of SNRIs include:

3. Atypical antidepressants

Atypical depressants, as the name suggests, are not typical antidepressants due to their distinct mechanism of action.

Atypical antidepressants increase dopamine, serotonin, or norepinephrine levels in the brain. They have multiple mechanisms of action and are commonly prescribed when other antidepressants do not improve depression symptoms.

Some of the common atypical antidepressants include:

Some of the common side effects of atypical antidepressants include:

4. Serotonin modulators

These involve drugs that work to improve serotonin levels in the brain. They work by modifying one or more serotonin receptors and inhibiting the reuptake of serotonin.

Some of the commonly used serotonin modulators include:

  • Nefazodone
  • Trazodone
  • Vilazodone
  • Vortioxetine

Some of the side effects of serotonin modulators include:

5. Cyclic antidepressants

There are two types of cyclic antidepressants depending on their structure: tricyclic and tetracyclic antidepressants. They prevent the reuptake of serotonin and norepinephrine in the brain, thus elevating mood and alertness.

Tetracyclic and tricyclic antidepressants prevent the reuptake of norepinephrine and serotonin into the nerves. It increases the level of norepinephrine and serotonin in the blood. They affect several other chemicals in the brain, thereby increasing the risk of side effects. Hence, they are not generally preferred by doctors to treat depression.

Some of the commonly used cyclic antidepressants are:

Common side effects of tetracyclic and tricyclic antidepressants include:

Other antidepressant rankings

6 most effective antidepressants sold in the United States

  1. Amitriptyline
  2. Effexor (venlafaxine)
  3. Lexapro (escitalopram)
  4. Paxil (paroxetine)
  5. Remeron (mirtazapine)
  6. Trintellix (vortioxetine)

5 most tolerated antidepressants

  1. Celexa (citalopram)
  2. Lexapro (escitalopram)
  3. Prozac (fluoxetine)
  4. Trintellix (vortioxetine)
  5. Zoloft (sertraline)

3 least effective antidepressants sold in the United States

  1. Luvox (fluvoxamine)
  2. Oleptro (trazodone)
  3. Prozac (fluoxetine)

6 least tolerated antidepressants sold in the United States

  1. Amitriptyline
  2. Anafranil (clomipramine)
  3. Cymbalta (duloxetine)
  4. Effexor (venlafaxine)
  5. Luvox (fluvoxamine)
  6. Oleptro (trazodone)

Side effects of various antidepressants

Table. The side effect profile for the top five antidepressants
Generic name Brand name
  • Dry mouth
  • Blurred vision
  • Trouble urinating
  • Constipation
  • Dizziness
Drowsiness Trouble sleeping, Jitteriness Nausea, Vomiting, Diarrhea Weight gain Sexual problems
Selective serotonin reuptake inhibitors (SSRIs)
Citalopram Celexa None None Very low Very low Very low Moderate
Escitalopram Lexapro None None Very low Very low Very low Moderate
Fluoxetine Prozac, Sarafem None None Low Very low Very low Moderate
Fluvoxamine Luvox (only sold as generic in the United States) None Very low Very low Very low Very low Moderate
Paroxetine Paxil, Pexeva, others Very low Very low Very low Very low Low High
Sertraline Zoloft None None Low Low Very low Moderate
Atypical agents
Bupropion Wellbutrin, Aplenzin, others None None

Quick-release: Low

Sustained-release: Very low
Very low None None
Mirtazapine Remeron Very low High None None High Very low
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Desvenlafaxine Pristiq, Khedezla None Very low Low Very low (after week 1) None Moderate
Duloxetine Cymbalta None None Low Low None Moderate
Levomilnacipran Fetzima Very low None Very low Low None Low
Milnacipran Savella None Very low None Low None Low
Venlafaxine Effexor None Very low Low

Quick-release: Low

Extended-release: Very low
None Moderate
Serotonin modulators
Trazodone Desyrel None High None

Sleep-aid dose: Very low

Antidepressant dose: Moderate

Sleep-aid dose: None

Antidepressant dose: Very low
Very low
Vilazodone Viibryd None None Low High None Low
Vortioxetine Trintellix None None Very low Very low Very low Low
Cyclic antidepressants
Amoxapine Asendin Low Low Low None Low Unknown
Maprotiline Ludiomil Low Moderate None None Low Unknown
Mirtazapine Remeron Low Moderate None None Very low None


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Medically Reviewed on 2/8/2022
Image Source: iStock Images

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American Academy of Family Physicians. Types of Antidepressants. https://familydoctor.org/types-of-antidepressants/