9 Bupropion (Wellbutrin) Interactions to Know About

Bupropion (Wellbutrin) is an atypical antidepressant medication. It works by raising the amount of dopamine and norepinephrine in the brain. These are hormones that are involved in regulating your mood.

Bupropion comes as immediate-release (IR), sustained-release (SR), and extended-release (ER) tablets. Bupropion SR (Wellbutrin SR), bupropion ER (Wellbutrin XL), and bupropion IR are common bupropion products. Other brand names — Aplenzin and Forfivo XL — are also available.

These bupropion products treat conditions like depression and seasonal affective disorder. Bupropion can also be used to help people quit smoking. Although bupropion can be an effective treatment option for several conditions, it can also interact with other medications. Here we’ll discuss nine bupropion interactions to know about.

Wellbutrin IR tablets are no longer available as a brand-name product.

1. Antiplatelet medications, such as Plavix

Bupropion is metabolized (broken down) in the liver. More specifically, it’s broken down by a protein (enzyme) called CYP2B6. Other medications that affect this enzyme can increase or decrease levels of bupropion in the body.

Medications that block CYP2B6 may increase bupropion levels. In these situations, you may need a lower bupropion dose. Examples include the antiplatelet medications called clopidogrel (Plavix) and ticlopidine.

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Even if you take an antiplatelet medication, don’t change your dose without talking to your prescriber first. They may just want you to monitor for bupropion side effects, such as tremors and trouble sleeping. Or, they may change your dose.

2. Antiseizure medications, such as carbamazepine

Other medications may decrease bupropion levels by increasing CYP2B6 levels in the body. If you take one of these medications, you may need a higher bupropion dose. Examples include:

• Carbamazepine (Tegretol, Tegretol XR)

• Phenobarbital

• Phenytoin (Dilantin, Phenytek)

As always, don’t change your dose without talking to your prescriber first. They may just want to monitor you for signs that bupropion isn’t working.

3. Antiviral medications, such as ritonavir

Like the seizure medications discussed above, some antiviral medications may decrease bupropion levels by increasing CYP2B6 levels in the body. If you take one of these medications, you may need a higher bupropion dose. Examples include:

• Ritonavir (Norvir) and any medications that contain ritonavir

• Efavirenz and any medications that contain efavirenz

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4. Antidepressants such as Lexapro, Zoloft, and trazodone

Bupropion blocks (inhibits) a liver enzyme called CYP2D6. This can lead to higher levels of medications metabolized by CYP2D6. Examples of these medications include:

• Serotonin and norepinephrine reuptake inhibitors (SNRIs),such as venlafaxine (Effexor XR)

• Selective serotonin reuptake inhibitors (SSRIs), such as Zoloft (sertraline), Prozac (fluoxetine), and Lexapro (escitalopram)

• Tricyclic antidepressants (TCAs), such as nortriptyline (Pamelor)

• Atypical antidepressants, such as trazodone

It’s also important to know that antidepressants aren’t the only medications bupropion can affect in this way. For example, bupropion can also increase levels of the antianxiety medication buspirone (formerly known as Buspar), or the antipsychotic medication risperidone (Risperdal). So give your prescriber or pharmacist a list of your medications before starting bupropion. They can check for interactions, and let you know if you need to change the dose of any of your medications.

5. Medications that increase your risk of seizures, including  Adderall, Abilify, and tramadol

Some medications can make it more likely for you to have a seizure. This is called lowering the “seizure threshold.” 

Bupropion is one medication that lowers the seizure threshold. The risk is greater with the IR form and with higher doses. And combining bupropion and other medications that lower the seizure threshold can increase your risk of seizures. Examples of these medications include:

• TCAs, such as amitriptyline

• Antipsychotics, such as Abilify (aripiprazole) and clozapine (Clozaril)

• Opioids, such as tramadol (ConZip, Qdolo)

• ADHD medications, such as Adderall (mixed amphetamine salts) 

• Cyclobenzaprine (Amrix)

• Diphenhydramine (Benadryl)

If you take other medications that lower the seizure threshold, let your prescriber know. They may recommend a lower dose of bupropion or recommend another antidepressant entirely.

It’s important to note that bupropion should be avoided completely in certain groups of people at higher risk of seizures. This includes people with epilepsy or a current or prior eating disorder. It also includes those who abruptly stop drinking alcohol or abruptly stop certain medications, like benzodiazepines.

6. Dopaminergic medications, such as Sinemet and ashwagandha

Medications that increase dopamine are used to treat Parkinson’s disease and restless leg syndrome. Examples include:

• Sinemet (carbidopa / levodopa)

• Levodopa (Inbrija)

• Amantadine (Gocovri)

• Ropinirole

• Pramipexole

Other medications and substances, such as ashwagandha, can also raise dopamine. Ashwagandha is an herbal supplement that has been studied and used for mental health benefits, such as decreasing stress levels.

Too much dopamine can cause toxicity in your nervous system, including symptoms like:

• Restlessness

• Tremors

• Dizziness (including vertigo)

• Agitation 

• Poor coordination

If you take any of these medications or ashwagandha, let your prescriber know before starting bupropion. They may recommend another antidepressant. They’ll also discuss more signs and symptoms of dopamine toxicity to watch out for.

7. ADHD medications, such as Adderall and Vyvanse

Attention deficit-hyperactivity disorder (ADHD) medications also increase dopamine levels. What’s more, they can also increase your blood pressure by increasing norepinephrine levels, which is a possible side effect of bupropion. When bupropion is combined with an ADHD medication, blood pressure increases may become more likely. Examples of ADHD medications include Adderall and Vyvanse (lisdexamfetamine).

Your risk of significantly increased blood pressure from either bupropion or ADHD is minimal. But when combined, it’s more likely, especially if you already have high blood pressure. So make sure your prescriber knows if you take an ADHD medication before starting bupropion.

It’s also important to note that ADHD medications aren’t the only medications that increase blood pressure. Several medications can do this, along with everyday substances such as caffeine. So if you have high blood pressure (hypertension), your prescriber may recommend checking your blood pressure more often at home while taking bupropion.

8. Monoamine oxidase inhibitors, such as linezolid and selegiline

Monoamine oxidase inhibitors (MAOIs) can treat depression and Parkinson’s disease. Taking MAOIs and bupropion together increases your risk of developing dangerously high blood pressure. This includes a medical emergency like hypertensive crisis. 

This interaction is thought to occur because bupropion and MAOIs both raise levels of norepinephrine. Examples of MAOIs include linezolid (Zyvox), phenelzine (Nardil), and selegiline (Zelapar, Emsam).  

You shouldn’t take bupropion and MAOIs at the same time. In fact, you shouldn’t even take them within 2 weeks of each other. This means that if you’re starting bupropion, you shouldn’t take an MAOI within 2 weeks before or after your first dose. 

9. Alcohol

Alcohol has effects on many body systems, including the brain. Combining bupropion and alcohol may affect your brain. It can lead to a higher risk of having suicidal thoughts or behaviors. It may also affect your ability to concentrate and it can make you dizzy. For someone who drinks heavily, seizures can also occur as part of alcohol withdrawal. And since bupropion also raises your risk of seizures, the combination can make seizures more likely.

Bupropion can also lower your tolerance for alcohol. This means you may not be able to drink as much alcohol as you did when you weren’t taking bupropion. If you or someone you know experiences alcohol poisoning, call 911 right away.

It’s best to avoid drinking while on bupropion. If you drink alcohol and you don’t think you’ll be able to stop while taking bupropion, let your prescriber know. They may recommend an alternative to bupropion.

Will bupropion cause false positives on a drug test?

Drug tests can detect the presence of certain substances and medications in the body. Unfortunately, it’s possible to get false positive results on drug tests. Sometimes the false positive is caused by medications you take. 

Bupropion is one of several medications that may cause a false positive on a urine drug test. Taking bupropion can lead to false positive results for amphetamines or methamphetamine. This includes prescription amphetamines used to treat attention-deficit hyperactivity disorder (ADHD), like Adderall and Vyvanse. Talk to your healthcare team if you’re concerned about false positive results on a drug test.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Jennifer Gershman, PharmD, CPh, PACS

Jennifer Gershman, PharmD, is a licensed pharmacist in Florida. She has worked in the pharmacy industry for more than 15 years and is currently a medical writer.

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