What Is an NDRI?

A Class of Drugs Used to Treat Depression

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Norepinephrine-dopamine reuptake inhibitors (NDRIs) are a class of drugs used primarily to treat depression.

They can also be used to treat attention deficit hyperactivity disorder (ADHD), depression, narcolepsy, and Parkinson's disease.

They are a newer class of antidepressants used to treat depression and tend to have fewer side effects than other common antidepressants. 

What NDRIs Do

Norepinephrine and dopamine are chemical messengers in the brain that might cause mood disorders like depression and anxiety when they malfunction.

Norepinephrine is responsible for regulating your alertness and concentration, while dopamine regulates your mood.

NDRIs work by inhibiting the reuptake of norepinephrine and dopamine into the brain.

While they are similar to other reuptake inhibitor drugs like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the sense that they all inhibit the reuptake of chemical messengers, they focus on inhibiting norepinephrine and dopamine instead of serotonin.

They do this by blocking the actions of the norepinephrine and dopamine transporters. 


NDRIs are typically used when other forms of antidepressants like SSRIs don’t produce effective results or cause bothersome side effects. They are usually used to treat the following conditions:

  • Depression: The most common NDRI used for treating depression is bupropion. It has fewer side effects than other antidepressants, but might not be as effective as other antidepressants in treating more severe forms of depression. A 2016 review of 51 studies on the effectiveness of bupropion as an antidepressant found that the drug is effective either alone or in combination with other antidepressants for treating depression.
  • ADHD: Antidepressants are sometimes prescribed to treat ADHD symptoms as an alternative to stimulant medication. Wellbutrin is the most common NDRI used to treat ADHD. It might sometimes be prescribed alongside other ADHD medication like Adderall. 
  • Narcolepsy: Narcolepsy is a condition that causes excessive daytime sleepiness. In 2019 the FDA approved Sunosi (solriamfetol), which is an NDRI for the treatment of narcolepsy. Solirameftol helps promote wakefulness in people with this condition.
  • Parkinson’s disease: Sometimes Parkinson’s disease is accompanied by depression. In these cases, NDRIs might be used to treat the depressive symptoms in people who have the disorder. 
  • Smoking cessation: If you find yourself unable to quit smoking, by sheer force of will, this might be because you’ve developed an addiction to nicotine, which is found in large quantities in cigarettes. NDRIs are approved to help you quit smoking by reducing your nicotine cravings.  

Types of NDRIs

There are currently three main types of NDRIs approved for use in the United States for different conditions. 


Dexmethylphenidates are drugs that are typically used for the treatment of ADHD. It can also be used to treat some form of depression.

The brand name version of dexmethylphenidate is Focalin. It’s essential to know that Focalin can be habit-forming.

You shouldn’t take it for longer than prescribed or take more quantities than your prescription advises.

Some of the most common side effects you might experience when using Focalin include nausea, dizziness, heartburn, and headaches.


Methylphenidate is a drug used to treat ADHD in adults and children. It’s typically sold under the brand name Ritalin.

Ritalin is also used for the treatment of narcolepsy in adults. You might also recognize methylphenidate by other brand names like Concerta, Methylin, and Metadate.

Methylphenidate is typically used alongside other treatment options like behavior therapy when being used to treat ADHD. It helps to increase the attention span and reduce symptoms of hyperactivity and impulsivity in people with the condition. 


The most common brand name of the drug available is Wellbutrin. Wellbutrin is primarily used to treat major depressive disorder. It’s also commonly used off-label to treat ADHD.

Bupropion is currently the only NDRI approved for treating depression by the FDA. It’s also available under other brand names like Zyban and Alpezin.

A 2016 review on the effectiveness of bupropion as a treatment for depression, found that the medication was highly effective in treating depression symptoms both when used on its own or alongside other depression treatments. 

Wellbutrin is often used together with an SSRI for treating depression. In 1997, the FDA also approved it for use as a smoking cessation aid, to help people with nicotine dependence quit smoking. 

Other NDRIs that aren’t as common as those listed above include: 

  • Survector (amineptine)
  • Cleofil (difemetorex)
  • Glucoenergan (fencamfamine)
  • Phenotropil (phenylpiracetam)
  • Catovit (prolintane)

Side Effects 

NDRIs are a commonly preferred treatment option for depression because they have fewer side effects that are common to other antidepressants such as sexual dysfunction.

However, NDRIs do cause some side effects that are mostly mild and tend to dissipate with a few weeks of use. 

  • Headache
  • Weight loss 
  • Anxiety 
  • Dry mouth
  • Constipation
  • Insomnia
  • Sweating
  • Loss of appetite 
  • Nausea
  • Vomiting 

In rare cases, you might experience some more serious side effects like high blood pressure and suicidal thoughts when using an NDRI. If you or a person you know starts to experience suicidal thoughts when using an NDRI, speak to your doctor immediately. 

Some other severe side effects you might experience while using an NDRI include vision loss, seizures, and tremors.

Warnings and Interactions 

It’s essential to keep an eye on your blood pressure when using this medication, as it might sometimes cause high blood pressure. Prolonged use of NDRIs can also cause a dependency on the drug and make it difficult for you to withdraw.

If your doctor notices you are developing a dependency on the medication, your doctor will no longer prescribe it to you or they will reduce your dosage.

When you stop using an NDRI after a dependency has already developed, you might experience some withdrawal symptoms like headaches, anxiety, insomnia, tiredness, nausea, and vomiting. 

Using an NDRI while using monoamine oxidase inhibitors is strongly cautioned against. In some cases, it can cause serotonin syndrome, a potentially life-threatening condition caused by the combination of certain drugs.

Using antipsychotic medication while using an NDRI could also increase your risk of developing a seizure. 

It is possible to overdose on an NDRI. Symptoms of an overdose include seizures, hallucinations, heart failure and loss of consciousness. If you suspect you, or a person close to you has overdosed on an NDRI, go to the emergency room immediately or call 911.

5 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Kaufman MB. Pharmaceutical Approval UpdateP T. 2019;44(6):337-339.

  3. Medline Plus. Dexmethylphenidate.

  4. Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. Therapeutic Advances in Psychopharmacology. 2016;6(2):99-144.

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By Toketemu Ohwovoriole
Toketemu has been multimedia storyteller for the last four years. Her expertise focuses primarily on mental wellness and women’s health topics.