Atypical antidepressants

Atypical antidepressants differ from other classes of antidepressants. Learn what they are and how they work.

By Mayo Clinic Staff

Atypical antidepressants are not typical — they don't fit into other classes of antidepressants. They are each unique medications that work in different ways from one another.

How atypical antidepressants work

Atypical antidepressants ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, atypical antidepressants work by ultimately effecting changes in brain chemistry and communication in brain nerve cell circuitry known to regulate mood, to help relieve depression.

Atypical antidepressants change the levels of one or more neurotransmitters, such as dopamine, serotonin or norepinephrine.

Atypical antidepressants approved by the FDA

The Food and Drug Administration (FDA) approved these atypical antidepressants to treat depression:

  • Bupropion (Wellbutrin SR, Wellbutrin XL, others)
  • Mirtazapine (Remeron)
  • Nefazodone
  • Trazodone
  • Vilazodone (Viibryd)
  • Vortioxetine (Trintellix)

A new antidepressant called esketamine (Spravato) is FDA approved for treatment-resistant depression. It's a nasal spray intended for use in combination with an oral antidepressant.

Possible side effects of atypical antidepressants

Side effects may occur with antidepressants, including atypical antidepressants, though some people may not experience any. Some side effects may go away after a time, while others may lead you and your doctor to try a different medication.

Because of the different ways atypical antidepressants work, each has unique characteristics and varying possible side effects. For example:

  • Most of the atypical antidepressants list dry mouth, dizziness or lightheadedness as possible side effects.
  • Some antidepressants may help you sleep and are best taken at night, while others may cause insomnia.
  • Some antidepressants may cause constipation, while others may increase the risk of diarrhea.
  • Some antidepressants may increase your appetite, resulting in weight gain, while others may cause nausea.
  • Some antidepressants are more likely than others to cause sexual side effects.

Which antidepressant is best for you depends on a number of issues, such as your symptoms and any other health conditions you may have. Ask your doctor and pharmacist about the most common possible side effects for your specific antidepressant and read the patient medication guide that comes with the prescription.

Safety issues

Atypical antidepressants are safe for most people. However, in some circumstances they can cause problems. For example:

  • Bupropion should not be used by people who have a seizure disorder or an eating disorder such as bulimia or anorexia.
  • Esketamine can cause serious side effects and must be administered by a psychiatrist or a primary care doctor in close communication with a psychiatrist who has expertise in administering this medication.
  • Mirtazapine has been associated with an increase in cholesterol. Mirtazapine is also associated with weight gain.
  • Nefazodone has been linked to liver failure in some people — don't take it if you already have liver problems.
  • Trazodone has been associated with rare cases of priapism — a persistent, usually painful erection not associated with sexual arousal. In rare cases, trazodone has been linked to heart rhythm problems (cardiac arrhythmias), so if you have heart disease, ask your doctor whether this medication is safe for you.
  • Vilazodone and vortioxetine may increase the risk of bleeding, especially in people taking other medications that increase the risk of bleeding.

For antidepressants that cause sleepiness, be careful about doing activities that require you to be alert, such as driving a car, until you know how the medication will affect you.

Other issues to discuss with your doctor before you take an atypical antidepressant include:

  • Antidepressants and pregnancy. Talk to your doctor about the risks and benefits of using specific antidepressants. Some antidepressants may harm your baby if you take them during pregnancy or while you're breast-feeding. If you're taking an antidepressant and you're considering getting pregnant, talk to your doctor or mental health professional about the possible risks. Don't stop taking your medication without contacting your doctor first, as stopping might pose risks for you.
  • Drug interactions. When taking an antidepressant, be sure to tell your doctor about any other prescription or over-the-counter medications, herbs or other supplements you're taking. Some antidepressants can cause dangerous reactions when combined with certain medications or herbal supplements.
  • Serotonin syndrome. Rarely, an antidepressant can cause high levels of serotonin to accumulate in your body. Serotonin syndrome most often occurs when two medications that raise the level of serotonin are combined. These include other antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort.
    • Symptoms of serotonin syndrome include anxiety, agitation, sweating, high fever, confusion, tremors, restlessness, lack of coordination, blood pressure changes and a rapid heart rate.
    • Seek immediate medical attention if you have any of these symptoms.

Suicide risk and antidepressants

Most antidepressants are generally safe, but the FDA requires that all antidepressants carry black box warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under 25 may have an increase in suicidal thoughts or behavior when taking antidepressants, especially in the first few weeks after starting or when the dose is changed.

Anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior. If you or someone you know has suicidal thoughts when taking an antidepressant, immediately contact your doctor or get emergency help.

Keep in mind that antidepressants are more likely to reduce suicide risk in the long run by improving mood.

Stopping treatment with atypical antidepressants

Atypical antidepressants aren't considered addictive. However, stopping antidepressant treatment abruptly or missing several doses may cause withdrawal-like symptoms. Symptoms will vary depending on how the drug works. This is sometimes called discontinuation syndrome. Work with your doctor to gradually decrease your dose.

Finding the right antidepressant

People may react differently to the same antidepressant. For example, a particular drug may work better — or not as well — for you than for another person. Or you may have more, or fewer, side effects from taking a certain antidepressant than someone else does.

Inherited traits may play a role in how antidepressants affect you. In some cases, where available, results of special blood tests may offer clues about how your body may respond to a specific antidepressant. However, other variables besides genetics can affect your response to medication.

When choosing an antidepressant, your doctor takes into account your symptoms, any health problems, other medications you take and what has worked for you in the past.

Typically it takes several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. Your doctor may recommend dose adjustments or different antidepressants, but with patience, you and your doctor can find a medication that works well for you.

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Oct. 04, 2019 See more In-depth

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