From the FDA Drug Label
Drugs Metabolized by CYP2D6 Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors Therefore, coadministration of bupropion hydrochloride extended-release tablets (XL) with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), 7. 3 Drugs That Lower Seizure Threshold Use extreme caution when coadministering bupropion hydrochloride extended-release tablets (XL) with other drugs that lower the seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids).
Key Considerations:
- Bupropion can be prescribed with an SNRI, but caution is advised due to potential increased exposure of the SNRI (e.g., venlafaxine) as a result of CYP2D6 inhibition by bupropion.
- Dose adjustment may be necessary for the SNRI, particularly for drugs with a narrow therapeutic index.
- Extreme caution is recommended when coadministering bupropion with other drugs that lower the seizure threshold, including certain antidepressants. 1
From the Research
Yes, Wellbutrin (bupropion) can be prescribed with Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) like venlafaxine (Effexor), duloxetine (Cymbalta), or desvenlafaxine (Pristiq). This combination is sometimes used in clinical practice, particularly for patients with depression who have not responded adequately to a single medication or who experience specific side effects. The combination works well because these medications have complementary mechanisms of action - SNRIs increase serotonin and norepinephrine levels, while bupropion affects dopamine and norepinephrine through different mechanisms. When combining these medications, doctors typically start with one medication at a standard dose (such as bupropion XL 150 mg daily or an SNRI at its starting dose) and add the second medication gradually after the first is established, monitoring for side effects. The combination may help address symptoms that persist with monotherapy or mitigate certain side effects like sexual dysfunction or fatigue. However, patients should be monitored for potential increased side effects such as elevated blood pressure, increased heart rate, excessive sweating, or anxiety. This combination should be managed by a healthcare provider who can adjust dosages based on individual response and tolerability, as suggested by studies such as 2. It's also important to consider the potential for serotonin toxicity, especially when combining bupropion with other serotonergic medications, as highlighted in 3. Additionally, studies like 4 have shown that bupropion is an effective and generally well-tolerated option in the treatment of major depressive disorder, with the newer formulations having the advantage of reduced frequency of daily administration. Overall, the decision to prescribe Wellbutrin with an SNRI should be based on individual patient needs and medical history, with careful monitoring and adjustment of dosages as needed. Key points to consider when prescribing this combination include:
- Starting with a standard dose of one medication and gradually adding the second medication
- Monitoring for side effects such as elevated blood pressure, increased heart rate, and anxiety
- Adjusting dosages based on individual response and tolerability
- Considering the potential for serotonin toxicity, especially when combining bupropion with other serotonergic medications.