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)
Bupropion can be taken with desvenlafaxine, but caution is advised as desvenlafaxine is a substrate of CYP2D6 and bupropion is a CYP2D6 inhibitor.
- Dose adjustment may be necessary when coadministering bupropion with desvenlafaxine.
- Monitoring for increased exposure of desvenlafaxine is recommended when coadministered with bupropion 1.
From the Research
Bupropion (Wellbutrin) can be taken with desvenlafaxine (Pristiq), but this combination should only be used under close medical supervision. These medications work differently - bupropion primarily affects dopamine and norepinephrine, while desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). When combined, they may provide enhanced antidepressant effects for people who don't respond adequately to single-medication treatment. However, this combination carries increased risks, including a higher chance of seizures (particularly at bupropion doses above 450mg daily) and potential for serotonin syndrome, though this risk is lower than with other combinations, as noted in a case report of serotonin syndrome induced by a combination of bupropion and SSRIs 2.
Some key points to consider when taking these medications together include:
- Increased risk of side effects such as increased blood pressure, heart rate, anxiety, insomnia, and excessive sweating
- Potential for pharmacokinetic interactions, as bupropion can affect the levels of other medications, such as venlafaxine, by inhibiting the cytochrome P450 2D6 pathway 3
- Importance of regular monitoring of blood pressure, heart rate, and mental health status
- Need for immediate medical attention if unusual symptoms occur, such as severe headache, confusion, rapid heartbeat, high fever, or muscle rigidity
The most recent and highest quality study on the use of bupropion in combination with other medications for the treatment of major depressive disorder suggests that bupropion can be an effective and generally well-tolerated option, with the advantage of less somnolence and sexual dysfunction compared to some other antidepressants 4. However, the specific combination of bupropion and desvenlafaxine has not been extensively studied, and therefore, caution and close monitoring are advised when using this combination in clinical practice.