NDRIs: what are they, uses, side effects, and risks

Most antidepressants can cause weight gain and sexual dysfunction. Bupropion, sold as Wellbutrin, is an exception. Bupropion might even help with mild weight loss. 

So, what makes bupropion so different from other antidepressants? It's in a different class of drugs. It's a norepinephrine-dopamine reuptake inhibitor (NDRI)—the only antidepressant available in this class. Keep reading to learn more about NDRIs, and specifically, bupropion.   

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Norepinephrine-dopamine reuptake inhibitors (NDRIs) are medications prescribed to treat depression and other disorders.

There are three types of NDRIs:

Bupropion

Bupropion is the only antidepressant NDRI on the market. Its most common brand name is Wellbutrin. It's also available under the brand name Zyban, a medication to help with quitting smoking. Bupropion may also treat attention-deficit hyperactivity disorder (ADHD), narcolepsy, and Parkinson's disease.

Methylphenidate

Methylphenidate is also used to treat ADHD, narcolepsy, and Parkinson's disease. It's available under the brand names Ritalin, Concerta, Metadate, and Methylin.

Dexmethylphenidate

Dexmethylphenidate is used to treat ADHD. It’s sold under the brand name Focalin.

In this article, we’ll focus just on the use of the NDRI bupropion to treat depression.

Bupropion is used to treat depression. Unlike other antidepressants, it doesn't have two of the most bothersome side effects many other antidepressants have: weight gain and sexual dysfunction. 

For people with serious concerns about these side effects or those who want to lose weight, bupropion may be prescribed as a first-line antidepressant or added to another antidepressant (Santarsieri, 2015).

Most of the time, other antidepressants, such as SSRIs, SNRIs, NaSSAs, and SMSs, are tried first. SSRIs in particular, such as sertraline (brand name Zoloft), or sometimes newer SNRIs, are often the first type of antidepressant medication prescribed for someone with depression. Bupropion is frequently a third- or fourth-line option (Patel, 2016). Bupropion may be added to other antidepressants, like SSRIs, if those medications aren't proving effective enough, even after increasing the dose (Santarsieri, 2015).

Scientists think that disorders like depression or anxiety may involve low levels of the brain chemicals serotonin, dopamine, and norepinephrine. These are all neurotransmitters, meaning they carry messages between nerve cells. After carrying a message, the nerve cells usually reabsorb them.

NDRIs prevent the reabsorption (reuptake) of dopamine and norepinephrine at the gaps between nerve cells in the brain. That means they can pass more messages between nerve cells, and nearby brain tissue has greater concentrations of the two chemicals (Sheffler, 2021).

First-line antidepressants are all pretty much alike in their effectiveness and safety (Wyska, 2019). NDRIs are similar to SSRIs in their effectiveness in treating depression (Santarsieri, 2015).

First-line antidepressant medications fail to help bout 30–40% of people (Wyska, 2019). For those people, many healthcare providers choose to add another type of antidepressant, such as bupropion (Santarsieri, 2015). Adding on a different kind of antidepressant can help if using just one type has failed. 

If standard treatment doesn't work for you, you may have what's called treatment-resistant depression. There are alternate options available for more complicated cases of depression. 

Bupropion was removed from the market after its initial release because it caused seizures in people with major depressive disorder. Later, it was released back to the market after studies showed it was safer at lower doses (Santarsieri, 2015).

Other side effects of bupropion include (Santarsieri, 2015):

• Insomnia

• Anxiety

• Dry mouth

• Headache

• Nausea

• Vomiting

Unlike many other antidepressants, bupropion doesn't cause sexual dysfunction or weight gain. It may even cause weight loss, which is desirable to some people (Santarsieri, 2015).

People with depression for whom weight gain or sexual dysfunction is a problem may want to consider taking bupropion (Patel, 2016). The medication can be used alone or added to current therapy.

Who shouldn’t take bupropion?

You shouldn’t take bupropion if you (Sheffler, 2021):

• Have seizures now or have had them in the past. You’re more likely to have a seizure while taking bupropion if you have liver disease, have had a head injury in the past, or abuse alcohol or drugs.

• Are taking sedatives or benzodiazepines

• Have been diagnosed with an eating disorder

• Are taking monoamine oxidase inhibitors (MAOIs) 

You should take bupropion only on the advice of your healthcare provider if you are breastfeeding. Although bupropion doses of up to 300 mg daily produce only low levels of the drug in breastmilk and are probably safe, there’s some concern that bupropion in breastmilk may potentially cause seizures in breastfed infants. It may be safer to use a different antidepressant when breastfeeding (Drugs and Lactation, 2021).

All antidepressants, including bupropion, carry an increased risk of suicide in children, adolescents, and young adults. There is no increased suicide risk beyond the age of 24 (U.S. FDA, 2009).

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Current version

July 15, 2021

Written by

Alison Dalton

Fact checked by

Steve Silvestro, MD

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About the medical reviewer

Steve Silvestro, MD, Ro

Dr. Steve Silvestro is a board-certified pediatrician and Associate Director, Clinical Content & Education at Ro.