Bupropion, known by brand names like Wellbutrin, is a widely prescribed antidepressant also used for smoking cessation [1.7.5]. It works as a norepinephrine-dopamine reuptake inhibitor (NDRI), altering brain chemistry to improve mood and reduce cravings [1.7.5]. While effective for many, its unique mechanism means it can interact negatively with numerous other substances. Understanding these interactions is crucial for patient safety.
Absolute Contraindication: Monoamine Oxidase Inhibitors (MAOIs)
The most critical drug interaction with bupropion involves Monoamine Oxidase Inhibitors (MAOIs). Taking bupropion concurrently with or within 14 days of using an MAOI is strictly contraindicated [1.2.3, 1.4.5]. MAOIs, which include drugs like phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), and linezolid (Zyvox), also increase levels of norepinephrine and dopamine [1.4.4, 1.4.5].
Combining them with bupropion can lead to a dangerous buildup of these neurotransmitters, potentially causing a hypertensive crisis—a sudden, severe increase in blood pressure that can be life-threatening [1.4.2, 1.4.4]. To prevent this, a 'washout' period of at least 14 days is required when switching between these medications [1.2.5, 1.4.1].
Drugs That Lower the Seizure Threshold
One of the most well-known risks associated with bupropion is that it can lower the seizure threshold, making a seizure more likely [1.5.4]. This risk is dose-dependent and increases significantly when bupropion is combined with other medications that also lower the seizure threshold [1.2.5, 1.5.3].
Patients with a history of seizures, eating disorders like anorexia or bulimia, or those abruptly discontinuing alcohol, benzodiazepines, or other sedatives should not take bupropion [1.2.3, 1.5.4].
Key medication classes that increase seizure risk with bupropion include:
- Other Antidepressants: Tricyclic antidepressants (TCAs) like amitriptyline and other antidepressants can increase seizure risk [1.5.2, 1.7.4].
- Antipsychotics: Medications such as aripiprazole (Abilify), clozapine, and risperidone can lower the seizure threshold [1.3.2, 1.5.2].
- Stimulants: ADHD medications like Adderall (amphetamine/dextroamphetamine) and Vyvanse (lisdexamfetamine) can increase the risk [1.5.2].
- Other Medications: The opioid tramadol, theophylline (used for asthma), and systemic corticosteroids are also known to increase seizure risk when taken with bupropion [1.2.2, 1.5.3].
The Role of Alcohol
Combining alcohol with bupropion is strongly discouraged. It can increase the risk of seizures, especially in those who drink heavily or are undergoing alcohol withdrawal [1.6.4, 1.6.5]. There have also been reports of reduced alcohol tolerance and adverse neuropsychiatric events, such as mood changes and hallucinations, in patients who drink while taking bupropion [1.6.2].
Interactions Involving Liver Enzymes (CYP450)
Bupropion is primarily metabolized in the liver by an enzyme called CYP2B6 [1.8.3, 1.8.6]. Medications that affect this enzyme can alter the levels of bupropion in the body.
- CYP2B6 Inducers: These drugs speed up the breakdown of bupropion, potentially making it less effective. Examples include the anticonvulsants carbamazepine (Tegretol) and phenytoin (Dilantin), and certain antivirals like ritonavir (Norvir) and efavirenz (Sustiva) [1.3.3, 1.3.6]. A higher dose of bupropion may be needed, but this must be managed carefully by a doctor.
- CYP2B6 Inhibitors: These drugs slow the breakdown of bupropion, increasing its levels and the risk of side effects. An example is the antiplatelet drug clopidogrel (Plavix) [1.3.6].
Conversely, bupropion itself is a strong inhibitor of another enzyme, CYP2D6 [1.7.6]. This means it can increase the concentration of other drugs that are metabolized by this enzyme, including:
- SSRIs and SNRIs: Such as fluoxetine (Prozac), sertraline (Zoloft), and venlafaxine (Effexor) [1.2.5, 1.7.6].
- Antipsychotics: Including haloperidol and risperidone [1.2.5].
- Beta-blockers: Like metoprolol [1.7.6].
- Type 1C Antiarrhythmics: Such as flecainide and propafenone [1.2.5].
When bupropion is used with these medications, a dose reduction of the other drug may be necessary [1.2.5].
Dopaminergic Drugs
Since bupropion increases dopamine levels, taking it with other drugs that also affect dopamine can lead to an increased risk of central nervous system side effects like restlessness, agitation, tremor, and dizziness [1.2.2]. This includes medications used for Parkinson's disease, such as levodopa (Sinemet) and amantadine [1.2.2, 1.3.3].
Bupropion Drug Interaction Comparison
| Drug Class / Substance | Example(s) | Primary Risk of Interaction | Management |
|---|---|---|---|
| MAOIs | Phenelzine, Linezolid | Hypertensive Crisis (dangerously high blood pressure) | Contraindicated. Do not use within 14 days of each other [1.2.3]. |
| Drugs Lowering Seizure Threshold | Tramadol, Antipsychotics | Increased risk of seizures | Use with caution or avoid; start with low doses and titrate slowly [1.5.3, 1.5.4]. |
| Alcohol | Beer, Wine, Spirits | Increased seizure risk, reduced alcohol tolerance, neuropsychiatric events | Minimize or avoid consumption [1.6.2, 1.6.3]. |
| CYP2D6 Substrates | Metoprolol, Sertraline | Increased levels of the other drug, leading to potential toxicity | Dose reduction of the other drug may be required [1.2.5, 1.7.6]. |
| CYP2B6 Inducers | Carbamazepine, Ritonavir | Decreased bupropion levels, reducing its effectiveness | May require an increased bupropion dose, managed by a doctor [1.3.3, 1.3.6]. |
| Dopaminergic Drugs | Levodopa, Amantadine | Increased risk of CNS side effects (restlessness, tremor, dizziness) | Use with caution and monitor for side effects [1.2.2, 1.3.3]. |
Conclusion
Managing treatment with bupropion requires a thorough understanding of its potential interactions. The most severe interactions involve MAOIs and drugs that lower the seizure threshold. Patients should always provide their healthcare provider with a complete list of all prescription medications, over-the-counter drugs, and supplements they are taking [1.3.1]. Open communication with a doctor is the best way to ensure bupropion is used safely and effectively, minimizing the risk of adverse events.
For more detailed information, consult the official FDA prescribing information or speak with a healthcare professional. Learn more at the FDA database [1.2.5]
