Atypical Antidepressants: Uses, most common brand names, and safety information

Medically reviewed by  Jamie Winn, PharmD

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Major depressive disorder (MDD) is a chronic mental health condition that is the most common mood disorder in the United States. It is estimated that 14.4% of Americans will have at least 1 episode of major depression in their lifetime.

Depression is thought to be caused by deficiencies in certain neurotransmitters such as dopamine, serotonin, and norepinephrine. Atypical antidepressants work differently than other medications used to treat symptoms of depression and other mental illnesses. The first atypical antidepressant approved for MDD by the U.S Food and Drug Administration (FDA) was Desyrel (trazodone) in 1981. Immediate-release Wellbutrin (bupropion) was approved in 1989 shortly after the introduction of Prozac (fluoxetine).

Atypical antidepressants are not typically first-line treatment for MDD, despite some having similar efficacy and fewer sexual side effects than other antidepressant medications. Treatment for depression is usually treated with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

The list below includes the best atypical antidepressants approved by the U.S. Food and Drug Administration (FDA) and their pricing:

List of Atypical Antidepressants

What are atypical antidepressants?

An atypical antidepressant doesn’t fit in with the other 4 major classes of antidepressants, which include SSRIs, SNRIs, tricyclic antidepressants, and monoamine oxidase inhibitors (MAOIs). This class of antidepressants contains drugs that have various mechanisms of action. Atypical antidepressants work like most antidepressants by altering your brain chemistry to treat depression. They are typically used if other medications did not improve your symptoms or if they caused significant side effects.

Atypical antidepressants can also be used to treat other conditions besides depression. For example, Remeron (mirtazapine) is used to treat insomnia and Wellbutrin (bupropion) is used as a smoking cessation aid.

Atypical antidepressants are typically oral medications. The frequency you take it will depend on the condition being treated. How long it takes to work will vary between each atypical antidepressant. You should see some symptom improvement within the first week, but it can take up to 8 weeks to see the full effects.

How do atypical antidepressants work?

Each atypical antidepressant has its own unique effect on the neurotransmitters in your brain. They typically all inhibit or alter the reabsorption of dopamine, serotonin, and/or norepinephrine. The combination of these neurotransmitters they act on will determine their therapeutic use and side effect profile.

Wellbutrin (bupropion) increases the amount of norepinephrine and dopamine (NDRI) available in the brain. It is the only antidepressant that doesn’t increase serotonin levels. It is the 3rd most prescribed antidepressant in the U.S.

Remeron (mirtazapine) is considered a noradrenergic and specific serotonergic antidepressant (NaSSA). It blocks the H1 histamine receptor, the alpha-2 adrenergic receptor, and multiple serotonin receptors. Remeron’s antidepressant effect is thought to be due to its antagonism of the 5-HT2C serotonin receptor.

The remaining atypical antidepressants increase serotonin in multiple ways including blocking the reuptake of serotonin and antagonizing serotonin receptors in the brain.

What conditions are atypical antidepressants used to treat?

Atypical antidepressants are a class of medications used in the treatment of depression and other conditions such as:

• Major depressive disorder
• Obsessive-compulsive disorder (OCD)
• Generalized anxiety disorder (GAD)
• Social anxiety disorder (SAD)
• Eating disorders such as bulimia

Are atypical antidepressants safe?

When taken as prescribed, atypical antidepressants are relatively safe and effective. Your prescribing physician should be aware of your medical conditions, including:

• Seizure disorder
• Bipolar disorder
• Heart disease
• Kidney disease
• Liver disease
• Hypertension (high blood pressure)
• Eating disorder
• Are pregnant or plan on becoming pregnant as they may cause fetal harm and/or death

You should also make sure they are aware of all the medications you take, including FDA-approved prescription drugs, over-the-counter medications, and supplements, as they may cause drug interactions:

• SSRIs such as Prozac (fluoxetine), Zoloft (sertraline), Lexapro (escitalopram), Paxil (paroxetine), Luvox (fluvoxamine), and Celexa (citalopram)
• SNRIs such as Cymbalta (duloxetine), Pristiq (desvenlafaxine), and Effexor XR (venlafaxine)
• Monoamine oxidase inhibitors (MAOI) such as Nardil (phenelzine) and Parnate (tranylcypromine).
• Tricyclic antidepressants (TCAs) such as Elavil (amitriptyline), Silenor (doxepin), Tofranil (imipramine), Surmontil (trimipramine), and Pamelor (nortriptyline)
• St. John’s wort, antipsychotics, and any other class of antidepressant that increases serotonin

Can you take atypical antidepressants while you are pregnant or breastfeeding?

There is limited data on whether atypical antidepressant use during pregnancy poses any risk to the fetus. There is a registry that monitors outcomes in women exposed to antidepressants during pregnancy. You can register by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

Most atypical antidepressants are excreted in breast milk. The developmental and health benefits of breastfeeding should be considered as well as the possible adverse events on the breastfed infant.

You should always discuss the risks and benefits of any medication you need with your doctor or mental health professional if you are pregnant, plan on becoming pregnant, or are breastfeeding.

What are the common side effects of atypical antidepressants?

Some common adverse effects of atypical antidepressants include:

• Constipation
• Dizziness
• Dry mouth
• Blurred vision
• Confusion
• Urinary retention
• Nausea
• Weight gain
• Drowsiness and sedation
• Sexual dysfunction
• Hyponatremia (low sodium levels)

Atypical antidepressants can sometimes cause rare, severe adverse effects, including:

• Serotonin syndrome
• Seizures
• Increased risk of suicidal thoughts or behavior, especially in adolescents and young adults under the age of 24
• Arrhythmias
• Liver damage
• Manic episodes
• Orthostatic hypotension (low blood pressure upon standing)
• Persistent, painful erection (priapism)

This is not a complete list of side effects and we encourage you to consult with your healthcare professional for medical advice about any possible side effects.

How much do atypical antidepressants cost?

Atypical antidepressants are very expensive with an average cost of around $5,000 per year for brand name medications.

You can purchase atypical antidepressants for $49 per month from NiceRx if eligible for assistance. Prices at the pharmacy vary by location, strength, and quantity, as well as your insurance status.

Related resources for atypical antidepressants

• https://www.ncbi.nlm.nih.gov/books/NBK519059/
• https://www.mayoclinic.org/diseases-conditions/depression/in-depth/atypical-antidepressants/art-20048208
• https://screening.mhanational.org/content/atypical-antidepressants/
• https://middlesexhealth.org/learning-center/articles/atypical-antidepressants
• https://www.rxlist.com/the_comprehensive_list_of_antidepressants/drugs-condition.htm
• https://www.statpearls.com/ArticleLibrary/viewarticle/17687
• https://digital.wpi.edu/downloads/qj72p7427
• https://doi.org/10.2174/9781681086071118060003