The Most Critical Contraindications
There are certain medications and substances that should never be combined with Wellbutrin (bupropion) due to the high risk of severe, and sometimes fatal, adverse events. These absolute contraindications must be respected to ensure patient safety.
Monoamine Oxidase Inhibitors (MAOIs)
The most critical interaction is with MAOIs, another class of antidepressants. This combination can cause a hypertensive crisis, a medical emergency involving a dangerous and sudden spike in blood pressure. The reason for this is that both bupropion and MAOIs increase levels of the neurotransmitters dopamine and norepinephrine. When taken together, this effect is dangerously amplified, leading to the hypertensive crisis. To prevent this, a waiting period of at least 14 days must pass after stopping an MAOI before starting Wellbutrin, and vice-versa.
Examples of MAOIs include:
- Isocarboxazid (Marplan)
- Linezolid (Zyvox)
- Phenelzine (Nardil)
- Selegiline (Emsam, Zelapar)
- Tranylcypromine (Parnate)
Other Bupropion Products
Patients should never take more than one product containing bupropion at a time. This includes taking Wellbutrin for depression while also using Zyban to quit smoking. Exceeding the maximum recommended dose of bupropion increases the risk of serious side effects, particularly seizures.
Abrupt Discontinuation of Alcohol, Sedatives, or Benzodiazepines
Suddenly stopping the use of alcohol or sedatives like benzodiazepines can lower the body's seizure threshold. Taking Wellbutrin under these circumstances further increases the risk of seizures. Healthcare providers will need to monitor and manage withdrawal safely before initiating Wellbutrin treatment.
Interactions Increasing Seizure Risk
Wellbutrin itself can lower the seizure threshold, and combining it with other drugs that have the same effect can substantially increase this risk.
- Antipsychotics: Certain antipsychotic medications, such as aripiprazole (Abilify) and risperidone (Risperdal), can interact with Wellbutrin.
- Stimulants: ADHD medications like amphetamine/dextroamphetamine (Adderall) and lisdexamfetamine (Vyvanse) increase dopamine and norepinephrine, raising the risk of seizures and blood pressure spikes when taken with Wellbutrin.
- Opioids and Tramadol: Opioid pain medications like tramadol can lower the seizure threshold, a risk compounded by bupropion.
- Tricyclic Antidepressants (TCAs): Older antidepressants such as amitriptyline and nortriptyline also increase seizure risk.
Interactions Affecting Drug Metabolism
Wellbutrin is a potent inhibitor of the CYP2D6 enzyme in the liver. This enzyme is responsible for metabolizing (breaking down) many other drugs. By inhibiting CYP2D6, Wellbutrin can cause other medications to build up in the body, potentially leading to increased side effects and toxicity.
- Other Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac) and sertraline (Zoloft), and serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine (Effexor XR) are metabolized by CYP2D6. Combining them with Wellbutrin can lead to higher levels of these drugs and increase the risk of side effects or serotonin syndrome.
- Antipsychotics: The levels of certain antipsychotics, like risperidone, can increase when combined with Wellbutrin.
- Beta-blockers: Medications for blood pressure and heart conditions, such as metoprolol, can have their levels increased by Wellbutrin.
Other Notable Interactions
- Dopaminergic Drugs: Combining Wellbutrin with drugs that also increase dopamine, such as levodopa and amantadine, can cause CNS toxicity. Symptoms may include agitation, restlessness, and gait disturbances.
- Anti-seizure Medications: Certain anti-seizure drugs, such as carbamazepine and phenytoin, can decrease the effectiveness of Wellbutrin by speeding up its metabolism.
- Alcohol: Drinking alcohol while taking Wellbutrin can increase the risk of seizures and worsen side effects like dizziness, drowsiness, and impaired judgment.
- Cannabis (Marijuana) and CBD: Cannabis and CBD products have been reported to interact with Wellbutrin, potentially affecting its efficacy and increasing side effects.
Comparing Wellbutrin Interactions
This table provides a quick reference for common drug interactions with Wellbutrin.
| Interacting Drug/Class | Examples | Type of Interaction | Potential Outcome |
|---|---|---|---|
| Monoamine Oxidase Inhibitors (MAOIs) | Isocarboxazid, Phenelzine | Absolute Contraindication | Hypertensive crisis (dangerously high blood pressure) |
| Other Antidepressants | SSRIs (Sertraline), SNRIs (Venlafaxine) | Increased Drug Levels (CYP2D6 Inhibition) | Increased risk of seizures or serotonin syndrome |
| Stimulants | Adderall, Vyvanse | Additive CNS Effect | Increased seizure risk, blood pressure, and heart rate |
| Antipsychotics | Abilify, Risperdal | Increased Drug Levels (CYP2D6 Inhibition) | Increased risk of seizures and side effects from the antipsychotic |
| Opioid Pain Meds | Tramadol | Additive CNS Effect | Increased seizure risk |
| Anti-seizure Meds | Carbamazepine, Phenytoin | Reduced Wellbutrin Levels | Decreased effectiveness of Wellbutrin |
| Alcohol | Alcoholic Beverages | Additive CNS Depression | Increased seizure risk, dizziness, and confusion |
What to Do If an Interaction Occurs
If you believe you have taken an interacting drug with Wellbutrin or are experiencing severe side effects, it is crucial to seek immediate medical attention. Never stop or change your medication dosage suddenly without consulting your doctor, as this can cause withdrawal symptoms or other serious health issues. Your healthcare provider can assess your symptoms, manage the interaction, and determine the safest course of action, which may include adjusting dosages or switching medications.
Conclusion
While Wellbutrin (bupropion) is a valuable medication for treating depression and other conditions, it is not safe for everyone. The potential for dangerous interactions with other medications, particularly MAOIs, stimulants, and drugs affecting seizure threshold, necessitates a thorough discussion of your complete medication list with your doctor or pharmacist. Furthermore, substances like alcohol and certain street drugs significantly increase the risk of adverse events, including seizures. Open communication with your healthcare team is the best defense against harmful drug interactions and ensures the safe and effective use of your medication.
This article is for informational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional before starting, stopping, or changing any medication.
