Bupropion (Wellbutrin, Zyban) Interactions: What You Need to Know

Bupropion is a prescription-only medication. Under the brand names Wellbutrin® and Wellbutrin XL®, it’s used to treat major depressive disorder. Wellbutrin XL is also used to help treat seasonal affective disorder (SAD). And sold under the brand name Zyban®, it’s used as a smoking cessation aid. 

Overall, bupropion is a safe and effective medication when it’s used as directed. However, like many other medications, it can interact with other drugs. Some of these interactions can result in side effects, and some can even be dangerous. 

Below, we’ve explained the basics of how bupropion works as a medication. We’ve also listed the interactions that can occur when bupropion is used with other medications, supplements and certain herbal products. 

How Does Bupropion Work? 

Bupropion is an antidepressant. It works by changing the levels of certain neurotransmitters in your brain. More specifically, bupropion increases the amount of dopamine and norepinephrine that are active in your body at any time.

Dopamine is an important neurotransmitter. It’s responsible for a range of functions within your body, including helping you feel motivated, boosting your mood and regulating your ability to learn, move and display emotional responses. 

Norepinephrine, on the other hand, is responsible for regulating your sleep-wake cycle, keeping you alert, allowing you to focus and helping you store new memories.

Although there’s debate about the precise cause of depression, research indicates that it might be linked to disturbances in serotonin, dopamine and norepinephrine levels.

As an antidepressant, bupropion works by inhibiting reuptake of the neurotransmitters dopamine and norepinephrine. This can help to improve your mood and treat the symptoms of depression and conditions such as seasonal affective disorder.

Interestingly, dopamine levels are affected by nicotine, with your body’s production of dopamine rising sharply after you smoke a cigarette. Due to bupropion’s effects on dopamine, it can make the cravings associated with quitting less intense — a topic we’ve covered in more detail here. 

Learn how to tell if Wellbutrin is working for you in our blog: 6 Signs Wellbutrin® is Working

Bupropion (Wellbutrin, Zyban) Drug Interactions

Overall, bupropion is a safe, effective medication when it’s used as prescribed. However, like other antidepressants, bupropion can interact with other medications. 

Some drug interactions may increase or decrease the effects of bupropion in the body. Others may have dangerous side effects, including potentially serious, life-threatening reactions that can occur when bupropion is used with other medications.

For any medication, including bupropion, the easiest way to avoid interactions is to inform your healthcare provider about all medications you currently use and have recently used. They will be able to review the safety of using bupropion and recommend the safest course of action for you. 

We’ve listed these interactions below, along with more information on the risks associated with each drug combination.

Bupropion (Wellbutrin, Zyban)

Bupropion is sold under several brand names as both a depression treatment (Wellbutrin) and as a medication for smokers interested in quitting (Zyban). 

Although it’s technically not an interaction, the FDA warns patients not to accidentally use more than one medication containing bupropion at the same time, as doing so may increase your risk of experiencing side effects such as seizures.

If you’re prescribed Wellbutrin, Zyban or a generic form of bupropion, make sure to check your other medications (particularly antidepressants or smoking aids) to ensure you aren’t using the same drug under a different brand name. 

Other brand names used for bupropion include Aplenzin®, Forfivo XL® and several others. Bupropion is also an ingredient in the weight loss medication Contrave®. 

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are a class of older antidepressants, many of which are still used to treat depression and several other conditions. Some commonly prescribed MAOIs include the following medications:

• Phenelzine (Nardil®)

• Isocarboxazid (Marplan®)

• Tranylcypromine (Parnate®)

• Selegiline (Emsam®)

Bupropion can interact with MAOIs, leading to an elevated risk of several side effects, including dangerously high blood pressure. As such, bupropion should not be used if you currently use a MAOI to treat depression or any other condition.

You should also avoid using bupropion if you’ve taken any MAOI medications within the past 14 days. Likewise, if you’re recently stopped using bupropion, avoid using any MAOIs until at least 14 days have passed since your most recent dose of bupropion. 

CYP2B6 Inducers

Bupropion is metabolized by the enzyme CYP2B6. Medications that increase the activity of the CYP2B6 enzyme, called CYP2B6 inducers, may make bupropion less effective in the body and necessitate a higher dosage.

CYP2B6 inducers include the antiretroviral medications ritonavir, lopinavir and efavirenz, which are commonly used in combination with other medications to treat HIV/AIDS. 

Other medications that can induce CYP2B6 and interact with bupropion include anticonvulsants such as carbamazepine (Tegretol®), phenytoin (Dilantin®) and phenobarbital.

If you’re prescribed any of these medications, it’s important to mention this to your healthcare provider before using bupropion. 

CYP2B6 Inhibitors

Likewise, medications that reduce the activity of the CYP2B6 enzyme, called CYP2B6 inhibitors, may increase the concentration of bupropion and other medications metabolized by CYP2B6 in the body.

Medications metabolized by CYP2B6 include several other antidepressants, such as paroxetine (Paxil®), sertraline (Zoloft®), fluoxetine (Prozac®), venlafaxine (Effexor®), desipramine (Norpramin® or Pertofrane®), imipramine (Tofranil®), nortriptyline (Pamelor®) and others.

Talk to your healthcare provider before using bupropion if you’re prescribed any other antidepressants. They may adjust your dosage of bupropion or recommend using a different medication. 

Other medications that can affect CYP2B6 levels and interact with bupropion include:

• Antipsychotics, such as haloperidol (Haldol®), risperidone (Risperdal®) and thioridazine (Mellaril®).
  
  

• Beta-blockers, including metoprolol (Lopressor®) and others.
  
  

• Type 1C antiarrhythmics, such as propafenone (Rythmol®), flecainide and others.

If you’re prescribed any of the medications listed above, or other medications in any of the drug classes listed above, make sure that you inform your healthcare provider before using bupropion. 

Dopaminergic Medications

Medications that affect dopamine, called dopaminergic medications, can interact with bupropion and cause central nervous system (CNS) toxicity. This could cause reactions such as dizziness, vertigo, agitation, tremor, restlessness, gait disturbance and loss of control over movement. 

Common dopaminergic medications include levodopa, or l-DOPA, and amantadine (Gocovri®), a medication used to treat certain viruses. Inform your healthcare provider if you currently use or have recently used either of these medications before using bupropion. 

Alcohol

Although rare, there have been reports of people experiencing a reduced alcohol tolerance or neuropsychiatric events after drinking alcohol while taking bupropion.

If you’re prescribed bupropion, drinking alcohol may increase your risk of experiencing negative side effects from both alcohol and bupropion. As such, it’s best to limit your alcohol consumption or avoid alcohol entirely while you take bupropion.

We’ve covered this topic in more detail, as well as what you can do to protect yourself from side effects associated with drinking while using bupropion, in our guide to bupropion and alcohol. 

Drug Tests

Bupropion may affect certain drug tests, causing false-positives. For example, some tests used to check for usage of amphetamines may show a false positive if you’re currently using or have recently used bupropion.

If you’re screened for illicit drugs as part of your employment, education or for any other reason, make sure to let the tester know that you’re prescribed bupropion. 

Bupropion (Wellbutrin, Zyban) Disease Interactions

If you have a pre-existing health condition or disease, you may be more at risk of experiencing side effects from bupropion. We’ve listed these interactions below, along with more information on what you can do to minimize your risk of experiencing an adverse reaction from bupropion.  

Liver and/or Kidney Problems

Bupropion is metabolized in the liver and kidneys. It may lead to temporarily elevated levels of aminotransferase, an enzyme found in the liver and kidneys that, in some cases, can indicate damage to the liver.

If you have liver and/or kidney problems, you may have a higher risk of experiencing negative side effects from bupropion. To avoid this, your healthcare provider may recommend taking bupropion at a reduced dosage, or for you to use a different medication. 

Seizure Disorders and/or Epilepsy

If you have a seizure disorder or epilepsy, using bupropion for any condition may increase your risk of experiencing seizures. As such, you should not use bupropion. Make sure to inform your healthcare provider if you have any seizure-related condition and want to use antidepressants.

Anorexia and Bulimia Nervosa

If you currently have or previously had an eating disorder, such as anorexia or bulimia nervosa, you may have an elevated risk of seizures if you use bupropion. 

As such, your healthcare provider may recommend an alternative medication to bupropion. 

Alcohol and/or Sedative Withdrawal

If you regularly drink a lot of alcohol and suddenly stop drinking, you may have an elevated risk of experiencing seizures if you use bupropion. This increase risk may also be present if you use the following medications and abruptly stop before using bupropion:

• Sedatives, including sleeping pills such as zolpidem (sold as Ambien®), eszopiclone and zopiclone.

• Benzodiazepines, including alprazolam (sold as Xanax®), diazepam (Valium®), lorazepam (Ativan®), clonazepam (Klonopin®) and others.

• Epilepsy and anti-seizure medications, such as carbamazepine (Tegretol) and other anticonvulsants.

As such, do not use bupropion if any of the above applies to you, and make sure you talk to your healthcare provider if they’re considering prescribing you bupropion.

High Blood Pressure (Hypertension)

Bupropion may cause increased blood pressure. If you have a history of high blood pressure, or currently use medication to lower your blood pressure, it’s important to talk to your healthcare provider about this before using bupropion.

Based on your overall health, your healthcare provider may recommend a different medication or ask you to occasionally monitor your blood pressure while using bupropion. 

Other Interactions

Bupropion may potentially interact with other medications and/or health conditions in addition to those listed above. Make sure to inform your healthcare provider about any medications you use, any health conditions you have or any other relevant information before using bupropion.

Learn More About Bupropion

Used as prescribed, bupropion is a safe and effective treatment for depression that can assist in your recovery. It’s also a proven, effective smoking cessation aid that can make it easier to deal with nicotine cravings when you’re trying to quit.

Interested in learning more about bupropion online? Our guide to bupropion lists everything you need to know about this medication, from how it works in your body to dosages, side effects, common questions and much more.