Wellbutrin Drug Interactions: What Not To Take With Bupropion?

Last Updated: June 10, 2020

Authored by Nena Messina, Ph.D.

Wellbutrin drug interactions have the potential to lead to serious health complications. This brings about the need to be adequately informed about all the drugs and substances that interact with particular medication before starting to take doses of it. Combining antidepressants like Wellbutrin with drugs or substances that react negatively will not only lead to physical damage to the organs, and will cause a strain on the patient’s mental health too in many cases. Take a look at Wellbutrin drug interactions with stimulants, antidepressants, opioids, and anticonvulsants, and various substances such as illicit drugs and alcohol.

Wellbutrin Interactions With Antidepressants

Bupropion, generic Wellbutrin, is classified as an NDRI antidepressant. Using it alongside other antidepressants such as MAOIs and SSRIs could lead to a more pronounced effect on the system. Their interactions will vary according to the specific type of antidepressant and may lead to mild, moderate, or severe adverse reactions.

Wellbutrin and Lexapro (Escitalopram)

Using Wellbutrin and Lexapro together will lead to a major drug interaction. It significantly increases the chances of the patient having seizures – something unlikely to happen if either drug is used alone. The chances of having a seizure become even more pronounced if the patient is elderly, undergoing withdrawal for a drug or alcohol, has a history of seizures or has a medical condition that affects the central nervous system (such as head trauma or a brain tumor).

Mixing Wellbutrin and Zoloft (Sertraline)

Bupropion and Zoloft are both metabolized by CYP2D6 (an enzyme that is expressed in the liver and the central nervous system). While clinical evidence of an interaction between the two may be lacking, plasma concentrations of selective serotonin reuptake inhibitors that are metabolized by CYP2D6 (such as Zoloft) may increase if combined with bupropion. Additionally, in- vitro studies show that sertraline restrains the hydroxylation of bupropion.

Wellbutrin and Buspar

While there are no scientifically established interactions between these two, user reports suggest that it could be a risky business. Users that took Wellbutrin and Buspar in the minimum doses reported that everything went normal, but users that took an increased dose of Wellbutrin alongside Buspar reported severe paranoia and hallucinations.

Woman experiencing hallucinations from wellbutrin

Wellbutrin and Prozac Interactions

The effect of a drug interaction between Wellbutrin and Prozac (Fluoxetine) is similar to the one with sertraline. CYP2D6 also metabolize Prozac, and this means that the plasma concentrations of the drug in the body may increase if it is combined with Wellbutrin.

Wellbutrin and Cymbalta

Using Wellbutrin and Cymbalta (Duloxetine) together leads to a moderate drug interaction. The adverse effects of Duloxetine are significantly increased due to the higher levels of serotonin activity in the body. It also increases the chances of the patient having the Serotonin syndrome, characterized by symptoms such as:

  • hallucinations,
  • confusion,
  • increased blood pressure and heart rate,
  • muscle spasms,
  • vomiting,
  • diarrhea.

Combining Wellbutrin and Xanax

Moderate drug interaction between Wellbutrin and Xanax is likely to occur if the patient is undergoing a sudden withdrawal from Xanax (alprazolam). If the patient has been using the drug for a long time, abrupt discontinuation may cause a trigger for seizures. The likelihood of this event is higher if the patient is also dosing on bupropion at the time.

Senior man suffering from seizures

Wellbutrin and Trazodone

The effects of combining these two are not as pronounced as with other antidepressants. This is because Trazodone is not chemically related to the selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) that are most commonly associated with substantial side effects.

Wellbutrin and Paxil (Paroxetine) Interactions

Paxil is an SSRI antidepressant. As established earlier with this sort of antidepressants, using Paxil at the same time with bupropion will lead to a moderate drug interaction. Serotonin levels in the body take a significantly longer time to reduce through hydroxylation, and the sustained high levels of serotonin expose the patient to the risk of serotonin syndrome.

Wellbutrin and Celexa

The mechanism of the interaction between these two drugs is not clearly established yet. However, a moderate pharmacokinetic interaction was observed between the two. Even though both drugs are metabolized by entirely different enzymes, reports show that bupropion increased the Cmax and AUC of citalopram by 30% and 40%, respectively.
Additionally, while the results of the use of Wellbutrin for anxiety symptoms vary with different users, using the drug with Celexa (also used for anxiety) may increase the severity of side effects.

Taking Wellbutrin and Klonopin Together

In patients that are already dosing on bupropion, excessive use of Klonopin or sudden discontinuation of the drug may trigger seizures. The patient is advised to speak first with the doctor before discontinuing or upping the dose of any medication prescribed.

Asian woman with sudden heart attack

Wellbutrin and Effexor

Individually, Wellbutrin and Effexor have slight chances of triggering a seizure in a patient. However, when used together, the chances of this are significantly increased, due in part to the higher levels of plasma concentration in the body. Patients with specific medical conditions that affect the central nervous system are more likely to experience these side effects than others.

Wellbutrin Interactions With Stimulants

Wellbutrin and Adderall

Combination of Wellbutrin and Adderall lead to a major interaction which is heavily influenced by the strength of the doses – particularly the Adderall dose. Excessive use of psychostimulants in itself already poses a significant risk to the health of the patient, and using it alongside bupropion is likely to be the final trigger that tips them over into experiencing seizures.

Wellbutrin and Vyvanse Interactions

CNS stimulants such as Vyvanse (Lisdexamfetamine) also lead to a major drug interaction with bupropion. The risk of seizures is increased with concurrent use, so extreme caution and close monitoring are strongly recommended if they have to be taken together.

Wellbutrin and Ritalin

Ritalin (Methylphenidate) is a drug that may lower the seizure threshold of a user, so it must be used with extreme caution and close guidance. If it must be used with bupropion, manufacturers recommend starting with a tiny dose and slowly titrating up to the minimum effective dose, while the patient is closely monitored.
Additionally, while the patient is slowly increasing doses of Ritalin, attempting to wean off bupropion slowly could be helpful too.

Wellbutrin Interactions With Opioids

Wellbutrin and Tramadol Drug Interactions

Using Wellbutrin and tramadol together leads to a major drug interaction. First of all, the concurrent administration of bupropion to a patient that is dosing on tramadol can affect the analgesic effects that the tramadol is supposed to have in the body. Secondly, for a drug like bupropion that reduces the seizure threshold, the administration of tramadol with bupropion can increase the risk of spasms.

 woman is suffering from spasm.jpg

Wellbutrin and Kratom

Kratom is known to have HT2a antagonistic effects. This would reduce GABA upregulation, increasing the risk of convultions when used at the same time with a drug like bupropion that reduces the seizure threshold, the chances of the patient having a seizure is increased – even more so if the patient is already dealing with medical conditions that affect the central nervous system.

Wellbutrin Interactions With Other Medications

Wellbutrin and Lamictal

Patients that already have pre-existing seizure disorders are advised to steer clear of bupropion. Using both drugs together would be counter-productive due to bupropion’s nature of reducing the seizure threshold. Additionally, bupropion may interact pharmacokinetically with anticonvulsant medication that triggers hepatic microsomal isoenzyme function. For the same reasons as are stated here, it is inadvisable to use Wellbutrin and Topamax together.

Wellbutrin and Abilify

Using Abilify (Aripiprazole) and Wellbutrin together can lead to a major drug interaction. Because Aripiprazole is partially metabolized by CYP2D6, manufacturers recommend that patients using the drug alongside bupropion (or similar drugs) should reduce the Aripiprazole dose to one-half of the usual dose. Then, the patient must be closely monitored.

Wellbutrin and Gabapentin Drug Interactions

Patients that have seizure disorders are advised to keep away from Wellbutrin, as well as take Gabapentin medication, as it tends to reduce the seizure threshold, increasing the risk of spasms.

Wellbutrin and Viagra

Some antidepressants are known to hurt the sexual life of the user. While bupropion sexual side effects are relatively mild, it would still be counter-productive to use the drug while treating erectile dysfunction with Viagra.

Depressed man with erectile dysfunction sitting on bed

Wellbutrin and Phentermine

Excessive use of the psychostimulant, Phentermine may be associated with an increased risk of seizures. Therefore, it is inadvisable to use the drug alongside bupropion due to its seizure threshold-reducing characteristics.

Wellbutrin and Benadryl Drug Interactions

Wellbutrin may trigger an increase in the blood pressure level and side effects of Benadryl (Diphenhydramine) in the body. If they must be used together, there should be a dose adjustment done by health professional along with close monitoring during the treatment process.

Wellbutrin Interactions With Other Substances

Wellbutrin and Marijuana

Patients are usually advised to steer clear of marijuana when using drugs such as bupropion, especially when starting the treatment. This is because, just like other psychoactive substances, marijuana may interfere with the effects of antidepressants on the central nervous system. Also, it makes it hard to determine if the medication is working or if a patient is experiencing side effects.

Wellbutrin and Caffeine

As suggested earlier, psychostimulants increase the risk of seizures when used alongside bupropion. Caffeine intake must be closely monitored in the diet of the patient, as it can be found in many drinks such as coffee, tea, colas, energy drinks, chocolate, and some herbal/dietary supplements.

Wellbutrin and Alcohol

Taking Wellbutrin and wine or other alcohol together will lead to harmful drug interactions. Alcohol is widely known for increasing the risk of side effects to appear in most drugs, and the case here is no different. It is always advised that patients should avoid or limit their intake of alcohol when receiving treatment.

Wellbutrin and MDMA

The use of MDMA during treatment with bupropion may lead to higher plasma concentration of both drugs in the system. It may also lead to enhanced mood effects but lower cardiac stimulation.

Wellbutrin and Cocaine

Cocaine is another example of substances that reduce the seizure threshold. When used alongside a drug like bupropion with a dose-related risk of seizures, the chances are increased. On that note, it is essential to keep a close watch of cocaine addicts that are dosing on the antidepressant, as they may attempt to get their high by snorting crushed bupropion.

An overall number of Wellbutrin interactions known is 811. It seems complicated for an average patient to know them all. That’s why it is imperative to provide a full medical history to a health professional to find out if it is safe for patients health to take Wellbutrin. In case one has any concerns about having other drugs in their system, it is advised to look for detox therapies to remove all traces of previous medications out of the body system.

Page Sources

  1. Xue C, Zhang X, Cai W, Prediction of Drug-Drug Interactions with Bupropion and Its Metabolites as CYP2D6 Inhibitors Using a Physiologically-Based Pharmacokinetic Model, https://www.ncbi.nlm.nih.gov/pubmed/29267251
  2. Schmid Y, Rickli A, Schaffner A, Duthaler U, Grouzmann E, Hysek CM, Liechti ME, Interactions between bupropion and 3,4-methylenedioxymethamphetamine in healthy subjects, https://www.ncbi.nlm.nih.gov/pubmed/25655950
  3. Dash RP, Rais R1, Srinivas NR, Chirality and neuropsychiatric drugs: an update on stereoselective disposition and clinical pharmacokinetics of bupropion, https://www.ncbi.nlm.nih.gov/pubmed/28876959

Published on: July 5th, 2019

Updated on: June 10th, 2020

About Author

Nena Messina, Ph.D.

Nena Messina is a specialist in drug-related domestic violence. She devoted her life to the study of the connection between crime, mental health, and substance abuse. Apart from her work as management at addiction center, Nena regularly takes part in the educational program as a lecturer.


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  • Lamonica Edwards
    Which is better to take with Clonazepam 0.5 MG? Bupropion HCL XL 300 MG Or Sertraline HCL 50MG