Atypical Antidepressants: Side Effects, Uses, And MOA

Last Updated: June 3, 2020

Authored by Sharon Levy, MD, MPH

For individuals who suffer from depression but have not had success with common depression-fighting medications, atypical antidepressants could be the solution they need. Atypical antidepressant drugs are so named because they act differently than those in the four main classes of depression-treating medications. Users interested in these medications need to research atypical antidepressant medications to ensure they are right for them.

What Are Atypical Antidepressants?

Atypical antidepressants are medications that have the ability to alleviate or eliminate symptoms of depression but do so in a way that is unlike the mechanisms of action seen in common antidepressants. The majority of these medications are not well-known, and many doctors will only prescribe them if other types of depression medications have been demonstrated not to work, or they have produced significant side effects.

The number of atypical depression medications is not as large as, say, that seen on a tricyclic antidepressants list. Additionally, some are used in other countries but have not been approved by the FDA for use in the U.S. However, there are multiple medications a doctor can choose from.

The list of atypical antidepressants with FDA approval is as follows:

Atypical Antidepressants Mechanism Of Action

Other classes of depression-fighting medications get their names based on a shared mechanism of action. For atypical antidepressants, the exact opposite is true—they get their name based on the fact that there is no mechanism of action that unites them. As such, the atypical antidepressant mechanism of action must be considered on a medication by medication basis.

All atypical antidepressant MOAs affect neurotransmitters in the brain, altering brain chemistry and changing communication within the brain’s circuitry. It is how they do this that varies. Some may target dopamine, others serotonin or norepinephrine, or any combination of the three.

How long it takes for antidepressants to work also varies between medications. However, like other depression-treating drug classes, effects tend to be felt somewhere between four and eight weeks after starting the medicine. This can be frustrating for people looking to feel better quickly, but it takes a while for the drugs to make a significant difference in brain chemistry.

woman uses atypical antidepressants at work

Atypical Antidepressant Uses

Given their name, it is easy to guess that atypical antidepressants are used for major depression treatment. However, this is not all that they can address. In fact, it is common to use some atypical antidepressants for anxiety more than for major depressive disorder.

Other conditions can be addressed with these medications as well. Depression that is not severe enough to be considered major depressive disorder might be treated with these medications. PTSD is also often addressed with atypical antidepressant drugs.

Less common uses include using them to manage

  • other mood disorders
  • ADHD
  • OCD
  • fibromyalgia
  • chronic neuropathic pain
  • even symptoms of menopause.

It is also possible that doctors will use weight loss antidepressant prescriptions to help obese patients get healthier. Antidepressants that increase energy may be used to help someone get active or fight fatigue from other conditions.

Atypical Antidepressants Side Effect

As with any medicine, these depression-treating medications have side effects. There are both short- and long-term effects of antidepressants that users need to consider. In many cases, these will be preferable to not treating depression or another condition, but not always. As such, users should be aware of them before they begin taking these drugs.

Atypical antidepressant side effects include:

  • Blurred vision
  • Feeling dizzy or lightheaded
  • Drowsiness
  • Feeling tired or weak
  • Dry Mouth
  • Headache
  • Confusion
  • Difficulty urinating
  • Fainting
  • Painful, sustained erections
  • Low blood pressure
  • Constipation
  • Nausea
  • Vomiting
  • Liver failure
  • Weight gain
  • Weight loss
  • Drop-in white blood cells
  • Increased cholesterol
  • Increased liver enzymes
  • Seizures
  • Sweating
  • Anxiety
  • Insomnia

In some cases, patients will be given the option to see if the side effects will go away with use or just live with them if they are less significant than the effects of their depression or other conditions. However, given that some of these side effects are dangerous or even deadly, the prescribing doctor may choose to have the patient discontinue use.

Contraindications And Warnings

Because there is such a variety within the atypical antidepressant drug class, users need to research their specific medication to know exactly what the contraindications and warnings are.

Some possible contraindications and warnings include:

  • Using in patients with seizure disorders
  • Using in patients with eating disorders
  • Using in patients who have a heart condition or high cholesterol
  • Using in patients with a compromised liver
  • Using in patients who have a bleeding disorder
  • Taking before or while operating heavy machinery
  • Taking during pregnancy or breastfeeding

woman is reading warnings and conterindications on the meds

It also must be noted that certain medications, foods, and street drugs cannot be used while taking certain medicines in this class. However, this varies and should be researched by the individual patient and their doctor. In general, all street drugs should be avoided, including mixing antidepressants and weed.

Finally, there is also the risk of serotonin syndrome developing. This is a potentially life-threatening condition that arises from mixing contraindicated medications.

When Atypical Antidepressants Are Misused

It is common for those using depression medication to want to stop their use. For these, users will benefit from substance abuse treatment. However, it should be noted that ending the use in the wrong manner can put the patient at risk. Stopping treatment with any medication is possible, as long as the patient seeks the right help.

While atypical antidepressants help many, they can also be misused and create more problems for the patient than they fix. Anyone who is abusing these medications or wants to stop them for other reasons should seek help from a drug rehabilitation center. With the correct facility, it is possible to safely stop medication use.

Page Sources

  1. Depression--Medicines To Help You. US Food & Drug Administration. 2008.
  2. Horst WD, Preskorn SH. Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion. Journal of Affective Disorders. 1998. 51 (3): 237-54.

Published on: October 15th, 2019

Updated on: June 3rd, 2020

About Author

Sharon Levy, MD, MPH

After successful graduation from Boston University, MA, Sharon gained a Master’s degree in Public Health. Since then, Sharon devoted herself entirely to the medical niche. Sharon Levy is also a certified addiction recovery coach.


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