Bupropion (Wellbutrin) Interactions: What You Need to Know

The world of antidepressants is a big one — we know. If this is your first time taking them, it’s okay to have tons of questions.

You see the commercials rambling about side effects and interactions and think, What actually are those things? Should I be worried? Is it safe? All fair questions.

Bupropion is a prescription-only antidepressant medication that helps people manage the symptoms of various mental health and mood disorders.

The medication can treat major depressive disorder (MDD) and seasonal affective disorder (SAD) and help with smoking cessation. It’s sold under the brand names Wellbutrin®, Wellbutrin SR®, Wellbutrin XL® (the extended-release version), Zyban® and Aplenzin®.

For the most part, bupropion is a safe and effective medication when used as directed. Yet, like any other medication on the market, it’s not perfect. It comes with an array of potential side effects ranging from mild to wild, and it can interact with other drugs. 

Below, we’ll dig into how bupropion interacts with other medications, alcohol, drug tests and pre-existing health conditions. That way, you’ll have all the info you need to make the best choice.

As noted, bupropion is a fairly safe prescription medication. It’s been approved by the U.S. Food and Drug Administration (FDA) since 1985 to treat several mental health conditions. However, the FDA’s medication guide says bupropion can negatively interact with other medications.

Certain drug interactions can increase bupropion effects. The adverse effects of taking bupropion with other medications may lead to drug interactions that can be mild or life-threatening.

Whenever you’re about to be prescribed bupropion or any other medication, tell your healthcare provider what other medications you’re currently taking (or have recently taken). They can provide medical advice and help you figure out if bupropion is the safest option for your health.

Ahead, find a list of medications that can cause drug interactions when taken with bupropion.

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs or MAO inhibitors) manage and treat neurological and mental health conditions. They work by stopping the body from reabsorbing neurotransmitters like serotonin (sometimes called “feel-good” brain chemicals).

Like bupropion, MAOIs are an antidepressant prescription medication.

Commonly prescribed MAOI medications include:

• Phenelzine (Nardil^®)

• Isocarboxazid (Marplan^®)

• Tranylcypromine (Parnate^®)

• Selegiline (Emsam^®)

Monoamine oxidase inhibitors have many adverse health effects, like dry mouth and insomnia. For this reason, they’re often not the first-line (or even second-line) of drugs for managing conditions like depression.

Only animal studies have been performed to determine the effects of MAOIs and bupropion. However, the FDA states that taking both at once is contraindicated, meaning it’s a risky treatment approach.

Taking MAOIs and bupropion may increase the risk of health conditions, including:

• Hypertensive disorders. This includes medical conditions like high blood pressure (hypertension).

• Anaphylactoid and anaphylactic reactions. These are potentially life-threatening allergic reactions.

• Stevens-Johnson syndrome. This rare disorder affects the skin and mucous membranes.

CYP2B6 Inducers

CYP2B6 inducers are enzymes that play a significant role in drug metabolism within the body.

CYP2B6 is a human gene shown to metabolize two to 10 percent of clinical drugs, including bupropion. Because of this, the enzyme makes the antidepressant less effective in the body, potentially requiring a higher bupropion dosage.

These are the most common CYP2B6 inducer medications that can interact with bupropion:

• Protease inhibitors. Ritonavir (Norvir^®), lopinavir (Kaletra^®) and efavirenz (Sustiva^® and Stocrin^®) are used in combination with other medications to treat HIV/AIDS.

• Anticonvulsants. Sometimes called antiepileptics, anticonvulsants — such as carbamazepine (Tegretol^®), phenytoin (Dilantin^®) and phenobarbital — are used to control seizures.

If you’re taking any of these medications, mention them to your healthcare provider before using bupropion.

CYP2B6 Inhibitors

CYP2B6 inhibitors reduce the activity of CYP2B6 inducers. As a result, they increase the concentration of bupropion and other medications that CYP2B6 inducers metabolize in the body.

Antidepressant medications metabolized by CYP2B6 include:

• Esketamine (Spravato^®)

• Vortioxetine (Trintellix^® and Brintellix^®) 

• Amitriptyline (Elavil^® and Vanatrip^®)

• Fluoxetine (Prozac^®)

• Mianserin (Tolvon^®)

• Sertraline (Zoloft^®)

• Citalopram (Celexa^®)

• Venlafaxine (Effexor XR^®) 

If you’re taking other antidepressants, tell your healthcare provider before starting bupropion. They may adjust the dosage or suggest another medication to prevent the negative side effects of bupropion.

Other medications that may affect CYP2B6 enzymes and cause serious side effects with bupropion are:

• Antipsychotics. This includes haloperidol (Haldol^®), risperidone (Risperdal^®) and thioridazine (Mellaril^®).

• Beta-blockers. Metoprolol (Lopressor^®) and other beta-blockers help minimize the physical effects of anxiety.

• Type 1C antiarrhythmics. These atrial fibrillation medications include propafenone (Rythmol^®) and flecainide (Tambocor^®), among others.

• Antimalarial drugs. These antiparasitic agents include artemether (Coartem^®) and artemisinin (Alaxin^®). 

• Systemic steroids. This includes prednisone (Prednisone Intensol^®) and hydrocortisone (Cortef^®).

Dopaminergic Medications

Dopaminergic agonists are medications that affect dopamine levels. They’re primarily used to treat patients with Parkinson’s disease.

These medications are also first-line drugs for treating restless legs syndrome (RLS), neuroleptic malignant syndrome and dopamine antagonist-induced hyperprolactinemia.

Bupropion is considered a dopamine reuptake inhibitor. This means it blocks dopamine transporter proteins to increase norepinephrine and dopamine neurotransmitters in the brain.

Norepinephrine plays a significant role in cognition, motivation, intellect and social interactions.

Dopamine is responsible for various bodily functions, including helping you feel motivated, boosting your mood and regulating your ability to learn, move and display emotional responses.

Taking dopaminergic medications and bupropion together increases the risk of adverse effects from both drugs.

Dopaminergic agonist medications that may interact with bupropion include:

• Levodopa (Sinemet^®)

• Amantadine (Symmetrel^®)

• Pramipexole (Mirapex^®)

• Ropinirole (Requip^®)

• Apomorphine hydrochloride (KYNMOBI^®)

• Rotigotine Transdermal System (Neupro^®)

Speak with a healthcare professional before taking bupropion if you’re currently on dopaminergic agonist medication.

Alcohol

It’s recommended not to mix bupropion and alcohol. Alcohol is a depressant that alters the brain’s chemicals, making any problems you’re facing seem much worse than they really are. It can also heighten the side effects of your medication.

Mixing alcohol with bupropion or Wellbutrin may lead to side effects like:

• Nausea

• Vomiting

• Dizziness

• Exhaustion

• Memory loss

• Increased risk of overdose and alcohol poisoning

As such, it’s best to limit your alcohol consumption or avoid it entirely when taking bupropion to reduce your chances of negative side effects.
We’ve covered this topic in more detail in our guide to bupropion and alcohol, including what you can do to protect yourself from side effects associated with drinking while using bupropion.

Drug Tests

Bupriopon may cause false positives on urine drug tests for amphetamines (prescription stimulants). The antidepressant can also show up on blood tests for prescription drugs. A false-positive test result for amphetamines may occur due to current or recent use of bupropion.

Before getting screened for illicit drugs as part of your employee onboarding process or for another reason, let your tester know you’ve been prescribed bupropion.

If you’re living with a certain health condition or illness, you may have a heightened risk of experiencing side effects from bupropion. 

We’ve listed these interactions below, along with more information on minimizing your chances of experiencing an adverse reaction from bupropion.  

Liver or Kidney Problems

If you have liver or kidney problems, you have a higher chance of experiencing negative side effects from taking bupropion. Bupropion is metabolized in the liver and kidneys by CPY2B6 enzymes.

Taking bupropion may lead to temporarily elevated levels of aminotransferase, an enzyme found in the liver and kidneys. This enzyme could indicate that the antidepressant is causing acute liver injury, although this occurrence is rare.

To avoid damage to your liver and kidneys, tell your healthcare provider about any pre-existing conditions. Depending on your needs and health history, they can recommend a lower dosage of bupropion or suggest a safer alternative medication.

Seizure Disorders

If you’ve been diagnosed with a seizure disorder, like epilepsy, bupropion may not be a safe medication. Taking bupropion may increase your risk of having seizures, potentially resulting in a head injury. 

According to the FDA, bupropion causes seizures in four out of every 1,000 patients who take up to 450 milligrams daily. This rate is higher than any other antidepressant on the market.

With this in mind, inform your healthcare provider if you have a seizure-related condition before starting a bupropion prescription.

Anorexia and Bulimia Nervosa

If you have an eating disorder like anorexia or bulimia nervosa, bupropion can increase your risk of seizures. Wellbutrin interactions can also cause weight loss, which could be dangerous for those with eating disorders who may already be underweight or face malnutrition.

If your healthcare provider is aware of your eating disorder, they may recommend an alternative medication to bupropion. 

Alcohol or Sedative Withdrawal

If you drink alcohol regularly, then suddenly stop, you might have a heightened risk of seizures while taking bupropion.

This increased risk can also occur if you stop taking the following medications before using bupropion:

• Benzodiazepines. Colloquially called “benzos,” these depressant medications include sleeping pills such as zolpidem (sold as Ambien^®), eszopiclone (Lunesta^®) and zopiclone.

• Epilepsy and anti-seizure medications. These prescription drugs include carbamazepine (Tegretol^®) and other anticonvulsants.

• Sedatives. Sedative medications include alprazolam (Xanax^®), diazepam (Valium^®), lorazepam (Ativan^®) and clonazepam (Klonopin^®).

Don’t use bupropion if any of the above applies to you. Make sure you talk to your healthcare provider if they’re considering prescribing bupropion.

In rare cases, this medication may result in suicidal thoughts, whether taken on its own or with other prescription drugs. If you’re having suicidal ideations, contact your healthcare provider or text or call the suicide hotline at 988 for immediate help.

High Blood Pressure (Hypertension)

If you have high blood pressure (hypertension), using the antidepressant bupropion could increase your blood pressure further.

Elevated blood pressure may cause headaches, dizziness and blurred vision. But for these adverse effects to occur, you must be taking high doses of bupropion.

In addition, Wellbutrin drug interactions may occur with antihypertensive treatments, such as lisinopril (the generic version of Zestril^® and Qbrelis^®).

Consult your healthcare provider if you have high blood pressure. They may recommend a different medication or suggest monitoring your blood pressure more frequently while using bupropion.

We’ve covered how the antidepressant bupropion can interact with different medications and health conditions, but this list is not exhaustive. There are more potential drug interactions to be aware of, like the possible side effects of taking Wellbutrin and Prozac together.

To protect your health and lower your risk of negative side effects, inform your healthcare provider of any medications you’re currently taking (or have recently taken), as well as any health conditions you have before using bupropion.

When used as directed, bupropion is a safe and effective antidepressant medication that can help manage and treat depression, anxiety, bipolar disorder, seasonal affective disorder and other mental health conditions. Beyond that, it’s shown to be an effective smoking cessation treatment to help cigarette users overcome nicotine addiction.

But like most other prescription medicines and over-the-counter supplements, bupropion drug interactions can negatively interact with other medications. So it’s important to speak with a healthcare professional before taking this drug. 

• Bupropion negatively interacts with other drugs. Research shows this antidepressant can cause side effects when taken with other medications, like MAOIs, CYP2B6 inducers and inhibitors, and dopaminergic agonists.

• Alcohol is a big no-no. Drink responsibly and avoid mixing alcohol with bupropion, as this combination can cause adverse side effects. This goes for sedatives too.

• Be wary when taking drug tests. Bupropion can cause false positives in blood and urine drug tests.

• Be cautious if you have pre-existing conditions. If you have a pre-existing medical condition, like high blood pressure or epilepsy, your healthcare provider may recommend another medication. They might also suggest more frequent monitoring of your health, as bupropion can worsen certain diseases. You should also let your provider know if you’re currently pregnant or breastfeeding.

You can get immediate release or sustained-release bupropion online following a virtual assessment with a licensed healthcare professional.

Want to learn more about this antidepressant first? Check out our guides to bupropion dosage, bupropion side effects and withdrawal from bupropion.

Also, if you’re looking for online psychiatry or online therapy, Hers offers a range of mental health services you can access from your phone or computer.