Atypical antidepressants: Uses, common brands, and safety info

Depression is one of the most common mental health conditions, and it can be treated through a number of ways. Certain antidepressants like SSRIs and SNRIs are often used as first-line treatments for depression. However, these antidepressants don’t work the same in everyone, and in many cases, atypical antidepressants are prescribed. Atypical antidepressants describe a group of drugs that have different mechanisms of action and thus, don’t belong to other classes of antidepressants. Atypical antidepressants may help treat depression by balancing certain neurotransmitters in the brain, such as serotonin, norepinephrine, or dopamine.

Continue reading to learn more about atypical antidepressants, their uses, and side effects.

What are atypical antidepressants?

An atypical antidepressant is an antidepressant that doesn’t belong to any of the main classes of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). Instead, this atypical class of antidepressants consists of drugs that work in unique ways. An atypical antidepressant is usually prescribed if you’ve tried another antidepressant that didn’t work to improve your symptoms of depression. Atypical antidepressants may also be prescribed if a previous antidepressant caused unwanted side effects, such as sexual dysfunction. In some cases, atypical antidepressants may be prescribed as a first-line treatment depending on your mental health condition and the desired effects of the drug.

Atypical antidepressants are generally used to treat major depressive disorder (MDD), otherwise known as depression. Certain atypical antidepressants may be preferred for different reasons. Desyrel (trazodone) and Remeron (mirtazapine) may be prescribed for people with depression who have trouble sleeping since these drugs can have sedative effects. Wellbutrin (bupropion) may be a preferred antidepressant for some people because it doesn’t cause sexual side effects.  

Some atypical antidepressants may also be used for other purposes in addition to the treatment of depression. Bupropion can be used to help people quit smoking, and it can also be used to prevent seasonal depression, or seasonal affective disorder. 

Atypical antidepressants usually come as oral tablets. Some atypical antidepressants may come as an orally-disintegrating tablet or an extended-release tablet. They’re usually prescribed to be taken once daily depending on the condition being treated. 

How do atypical antidepressants work?

Atypical antidepressants work in different ways to treat major depression. These antidepressant medications have different mechanisms of action that are unique, and they generally work to balance certain neurotransmitters, or chemical messengers, in the brain. Depending on the drug, an atypical antidepressant can increase levels of serotonin, norepinephrine, or dopamine. These neurotransmitters are believed to be involved with the regulation of mood, motivation, alertness, and awakeness, among other functions in the body.  

Wellbutrin XL, Wellbutrin SR (bupropion) 

Bupropion works by blocking the reuptake of norepinephrine and dopamine in the brain. In turn, this drug helps increase levels of norepinephrine and dopamine. It is different from many other antidepressants in that it doesn’t affect serotonin levels. 

Desyrel (trazodone), Serzone (nefazodone)

Trazodone and nefazodone work similarly as serotonin antagonists and serotonin reuptake inhibitors. They block a specific serotonin receptor called 5-HT2A and the reuptake of serotonin to increase levels of serotonin in the brain. 

Remeron (mirtazapine)

Mirtazapine works as a serotonin antagonist. It blocks the 5-HT2A and 5-HT3A receptors and increases the activity of serotonin on the 5-HT1A receptor. Mirtazapine also blocks alpha-2 and histamine H1 receptors. The inhibition of alpha-2 receptors stimulates the release of norepinephrine. 

Viibryd (vilazodone), Trintellix (vortioxetine) 

Vilazodone and vortioxetine work in similar ways to increase the release and activity of serotonin in the brain. They primarily work as serotonin reuptake inhibitors. However, they also act as serotonin agonists by activating serotonin receptors.

What are atypical antidepressants used for?

Atypical antidepressants have identical FDA-approved uses. They’re generally used for depression, although some atypical antidepressants may be used for other reasons.

• Major depressive disorder 

• Seasonal affective disorder 

• Smoking cessation

Atypical antidepressants may also be used off-label for anxiety disorders, bulimia, and other mental health conditions. 

Who can take atypical antidepressants?

Adults

Atypical antidepressants are FDA-approved to treat depression in adults. They may be prescribed once daily as an oral tablet, depending on the drug prescribed. Atypical antidepressants are often prescribed after a previous antidepressant medication has failed to improve depression symptoms. They may also be preferred for adults who experienced intolerable side effects, such as sexual dysfunction or weight gain, from other antidepressant medications.

Seniors

Older people may be able to take atypical antidepressants. However, they may need to be monitored more closely for side effects.

Children

Atypical antidepressants are not usually approved or recommended in children. 

Are atypical antidepressants safe?

Atypical antidepressants are generally considered safe and effective for the treatment of depression. Like other antidepressants, atypical antidepressants carry a black box warning of an increased risk of suicidal thoughts and behaviors, especially in children and adolescents. People taking atypical antidepressants may need to be monitored for signs of suicidality.

Recalls

• Mirtazapine tablets 7.5 mg [12/31/2019] (FDA notice)

  • Bottles labeled as containing 7.5 mg tablets of mirtazapine may contain 15 mg tablets of mirtazapine. 

Restrictions

People with kidney or liver problems should use caution when taking some atypical antidepressants. The dosage of these medications may be adjusted or reduced in those with kidney or liver problems.

You should tell your doctor about any medical conditions you have or other medications you may be taking, including prescription drugs, over-the-counter medications, and herbal supplements before taking an atypical antidepressant.

Tell your doctor if you have a history of any of the following before taking an atypical antidepressant:

• Seizures

• Bipolar disorder

• Heart problems

• High blood pressure

• Bleeding problems

• Alcohol or substance abuse disorders

You should also tell your doctor if you are pregnant or breastfeeding before taking an atypical antidepressant. The use of an atypical antidepressant may increase the risk of harm to an unborn baby or a breastfed infant. 

Are atypical antidepressants controlled substances?

No, atypical antidepressants are not controlled substances.

Common atypical antidepressants side effects

Atypical antidepressants may cause similar side effects, such as headache, drowsiness, and dry mouth. These side effects may differ depending on the drug prescribed. 

Wellbutrin XL, Wellbutrin SR (bupropion) 

• Headache

• Dizziness

• Dry mouth

• Nausea

• Constipation

• Dry mouth

Serious side effects of bupropion include seizures, high blood pressure, manic episodes, hallucinations, visual problems, and allergic reactions. 

Desyrel (trazodone), Serzone (nefazodone)

• Drowsiness

• Dry mouth

• Headache 

• Dizziness

• Weight loss 

Serious side effects of trazodone and nefazodone include orthostatic hypotension, or low blood pressure when changing from a standing to a sitting or lying position, and priapism, or a painful erection that lasts more than 6 hours. Other serious side effects include an irregular heartbeat (QT prolongation), serotonin syndrome, bleeding problems, manic episodes, vision problems, and low sodium levels in the blood (hyponatremia). The use of nefazodone may also increase the risk of liver damage.  

Remeron (mirtazapine)

• Increased appetite

• Weight gain

• Dry mouth

• Drowsiness

• Dizziness

Serious side effects of mirtazapine include a low white blood cell count, serotonin toxicity or serotonin syndrome, angle-closure glaucoma, abnormal heart rhythm, manic episodes, seizures, and low sodium levels in the blood (hyponatremia). 

Viibryd (vilazodone)

• Nausea

• Vomiting 

• Diarrhea

• Trouble sleeping

Serious side effects of vilazodone include serotonin syndrome, bleeding problems, manic episodes, seizures, angle-closure glaucoma, low sodium levels in the blood (hyponatremia), and sexual dysfunction. 

Trintellix (vortioxetine) 

• Nausea 

• Vomiting

• Constipation

Serious side effects of vortioxetine include serotonin syndrome, bleeding problems, manic episodes, angle-closure glaucoma, low sodium levels in the blood (hyponatremia), and sexual dysfunction. 

Other considerations with atypical antidepressants

The use of atypical antidepressants may increase the risk of suicidal thoughts and behaviors. Seek medical attention if you experience sudden changes in mood or if you start to experience suicidal thoughts. The risk of suicidal thoughts and behaviors may be higher in children and young adults than in adults. 

If treatment with atypical antidepressants is being stopped, the dosage of the medication should be tapered, or gradually reduced over time. Abrupt discontinuation of an antidepressant may lead to withdrawal symptoms, including dizziness, nausea, anxiety, irritability, insomnia, headache, and fatigue. In severe cases, seizures may develop after stopping treatment. 

The use of antidepressants can increase the risk of serotonin syndrome. Increased levels of serotonin can cause toxicity, which can include signs and symptoms like hallucinations, agitation, flushing, dizziness, seizures, tremors, vomiting, and diarrhea. Seek immediate medical attention if you experience signs or symptoms of serotonin syndrome. 

How much do atypical antidepressants cost?

Atypical antidepressants may come in generic and brand-name versions. The cost of these medications can vary depending on your insurance plan. If you have insurance coverage, you can consult your insurance provider or pharmacist to determine your copay. Those who are uninsured may have to pay the cash price of their medication. Savings options, like the SingleCare discount card, may help lower the cost of your medications at participating pharmacies if you are uninsured or underinsured.