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.

Atypical antidepressants ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, atypical antidepressants work by changing the levels of one or more of these naturally occurring brain chemicals.

Atypical antidepressants affect neurotransmitters including dopamine, serotonin and norepinephrine. Changing the balance of these chemicals seems to help brain cells send and receive messages, which in turn boosts mood.

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

  • Bupropion (Wellbutrin, others)
  • Mirtazapine (Remeron)
  • Nefazodone
  • Trazodone (Oleptro)

Common side effects with most antidepressants, including atypical antidepressants, include dry mouth, constipation, and dizziness or lightheadedness. 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. Because of the different way atypical antidepressants work, each also has unique characteristics and side effects.

Bupropion may be a good choice if you have low energy caused by depression or if you're trying to quit smoking. It's sometimes prescribed to ease nicotine cravings under the brand name Zyban. Bupropion doesn't cause sexual side effects or weight gain as several other antidepressants do, and it's sometimes prescribed to counter the sexual side effects of another antidepressant. However, bupropion can cause or worsen anxiety in some people. Additional side effects, among others, may include:

  • Headache
  • Weight loss
  • Nausea and loss of appetite
  • Increased heartbeat
  • Insomnia

Mirtazapine is generally taken before bed because it can make you sleepy. Additional side effects, among others, may include:

  • Increased appetite
  • Weight gain
  • Increased cholesterol and triglycerides

Nefazodone may help ease anxiety as well as depression, but it can make you sleepy. It seems less likely to cause sexual side effects than do some other antidepressants. Additional side effects, among others, may include:

  • Headache
  • Insomnia
  • Weakness
  • Agitation
  • Nausea
  • Low blood pressure
  • Blurred vision

Trazodone causes sleepiness and can help with anxiety. Like mirtazapine, it's usually taken at bedtime. It may be prescribed alone or along with other antidepressants to help with sleep. Additional side effects, among others, may include:

  • Blurred vision
  • Headache
  • Extreme tiredness (fatigue)
  • Nausea
  • Muscle aches or pains
  • Diarrhea
  • Irregular heartbeat
  • Sudden drop in blood pressure when standing (orthostatic hypotension)

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

  • Bupropion has been linked to seizures in some people, especially at higher doses. It can also increase blood pressure. Bupropion may not be a good antidepressant for you if you have an eating disorder such as bulimia or anorexia.
  • Mirtazapine has been associated with an increase in cholesterol. Your doctor may recommend that you have periodic cholesterol tests if you take this medication.
  • Nefazodone has been linked to liver failure in some people. Don't take it if you already have liver problems. Call your doctor immediately if you have signs and symptoms of liver failure, such as yellowing of your skin or the whites of your eyes, unusually dark urine, loss of appetite, nausea, or abdominal pain.
  • Trazodone has been associated with a rare condition called priapism — a persistent, usually painful erection not associated with sexual arousal. If you have an erection that lasts for more than four hours or other symptoms, such as pain, seek emergency treatment. In rare cases, trazodone has been linked to heart rhythm problems (cardiac arrhythmias). If you have heart disease, talk to your doctor about whether this medication is safe for you.

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

  • Antidepressants and pregnancy. 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 provider about the possible dangers. Don't stop taking your medication without contacting your doctor first.
  • Drug interactions. When taking an antidepressant, be sure to tell your doctor about any other medications or supplements you're taking. Some antidepressants can cause dangerous reactions when combined with certain medications or herbal supplements.
  • Serotonin syndrome. Rarely, an atypical antidepressant can cause dangerously high levels of serotonin. This is known as serotonin syndrome. It most often occurs when two medications that raise serotonin are combined. These include other antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Signs and symptoms of serotonin syndrome include anxiety, agitation, sweating, confusion, tremors, restlessness, lack of coordination and rapid heart rate. Seek immediate medical attention if you have any of these signs or symptoms.

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.

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.

Each person reacts differently to a particular antidepressant and may be more susceptible to certain side effects. Because of this, one antidepressant may work better for you than another, or they may be used in combination. When choosing an antidepressant, your doctor will take into account your symptoms, your health problems, other medications you take, and what has worked for you in the past.

Inherited traits 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 particular antidepressant. The study of how genes affect a person's response to drugs is called pharmacogenomics. However, other variables besides genetics can affect your response to medication.

Typically it takes several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. You may need to try several antidepressants before you find the right one, but hang in there. With patience, you and your doctor can find a medication that works well for you.

June 25, 2016