From the Guidelines
Wellbutrin (bupropion) and fluoxetine (Prozac) can be prescribed together, but this combination requires careful medical supervision due to potential interactions, as noted in studies such as 1 and 2. The main concern is an increased risk of seizures, especially at higher doses of bupropion, as well as the potential for serotonin syndrome, a rare but serious condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness. Some key points to consider when prescribing these medications together include:
- Fluoxetine is a strong inhibitor of the CYP2D6 enzyme, which metabolizes bupropion, potentially increasing bupropion blood levels and side effects, as discussed in 3.
- The combination of bupropion and fluoxetine may be used intentionally to address depression that hasn't responded to single-medication approaches, as bupropion primarily affects dopamine and norepinephrine while fluoxetine affects serotonin, potentially providing broader neurotransmitter coverage, as mentioned in 4.
- Doctors typically start with lower doses and monitor closely for side effects when prescribing these medications together.
- It's essential to never adjust these medications without consulting a healthcare provider, given the potential risks and interactions involved, as emphasized in 1 and 2.
From the FDA Drug Label
7. 6 MAO Inhibitors Bupropion inhibits the reuptake of dopamine and norepinephrine. Concomitant use of MAOIs and bupropion is contraindicated because there is an increased risk of hypertensive reactions if bupropion is used concomitantly with MAOIs.4 CONTRAINDICATIONS
• The use of MAOIs (intended to treat psychiatric disorders) concomitantly with bupropion hydrochloride extended-release tablets (XL) or within 14 days of discontinuing treatment with bupropion hydrochloride extended-release tablets (XL) are contraindicated
2 Potential for Bupropion Hydrochloride Extended-Release Tablets (XL) to Affect Other Drugs 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)
Contraindications with wellbutrin and fluoxetine include:
- Increased risk of seizures when used concomitantly with other drugs that lower the seizure threshold, such as other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids.
- Increased exposures of fluoxetine when coadministered with bupropion due to CYP2D6 inhibition. However, there is no direct contraindication of using wellbutrin and fluoxetine together, but caution is advised due to the potential for increased fluoxetine exposure and the risk of seizures. 5, 6, 7
From the Research
Contraindications with Wellbutrin and Fluoxetine
- The combination of bupropion (Wellbutrin) and selective serotonin reuptake inhibitors (SSRIs) like fluoxetine can increase the risk of serotonin syndrome, a potentially fatal complication 8.
- Serotonin syndrome is characterized by symptoms such as neuromuscular hyperactivity, autonomic instability, and altered mental status, with clonus as a key distinguishing feature 9.
- The risk of serotonin syndrome may be increased when bupropion is combined with fluoxetine due to bupropion's inhibition of the cytochrome P450 2D6 pathway, which can increase blood levels of SSRIs 8.
- There have been reports of delayed-onset serotonin syndrome in patients taking a combination of fluoxetine and bupropion, highlighting the importance of monitoring patients for symptoms of serotonin syndrome even after several days of treatment 10.
- While the combination of bupropion and SSRIs like fluoxetine can be effective in treating major depressive disorder, it is generally recommended to use caution and monitor patients closely for signs of serotonin syndrome 11.
Key Considerations
- Bupropion can potentiate serotonin levels and lead to serotonin syndrome, even when used alone 12.
- The combination of bupropion and SSRIs like fluoxetine should be used with caution, and patients should be monitored closely for signs of serotonin syndrome 8, 9, 10, 12.
- Treatment of serotonin syndrome typically involves discontinuing the offending agent, providing supportive care, and using medications such as benzodiazepines and cyproheptadine to manage symptoms 9.