Is Wellbutrin (bupropion) safe to take with fluoxetine?

From the Guidelines

Taking Wellbutrin (bupropion) together with fluoxetine is generally considered acceptable under proper medical supervision, though this combination requires careful monitoring. These medications can work well together as they affect different neurotransmitters - fluoxetine primarily affects serotonin while Wellbutrin affects dopamine and norepinephrine. This combination is sometimes prescribed for depression that hasn't responded adequately to a single medication. However, there are important considerations to be aware of, such as the potential for increased risk of serotonin syndrome, though this is relatively uncommon with this specific combination, as noted in studies evaluating second-generation antidepressants 1.

Key Considerations

• Both medications can potentially lower seizure threshold, and when combined, there may be an increased risk of serotonin syndrome.
• Side effects might include increased anxiety, insomnia, or elevated blood pressure.
• Dosing typically starts with one medication stabilized before adding the second, with gradual increases as needed.
• It's essential that this combination be prescribed and monitored by a healthcare provider who can assess your specific medical history, current medications, and individual risk factors, as recommended by guidelines for treating depressive disorders 1.
• Never adjust these medications on your own, and report any unusual symptoms promptly to your doctor.

Monitoring and Safety

Regular monitoring is crucial when taking this combination, as advised by the American College of Physicians 1, to assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy. Patients should be monitored for the emergence of agitation, irritability, or unusual changes in behavior, because these symptoms can indicate that the depression is getting worse. The risk for suicide attempts is greater during the first 1 to 2 months of treatment, and SSRIs like fluoxetine are associated with an increased risk for suicide attempts compared with placebo 1.

Conclusion is not needed as per the guidelines, the above information is sufficient to make a decision.

From the FDA Drug Label

Drugs metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline),

• Bupropion (Wellbutrin) can increase concentrations of fluoxetine due to its inhibition of CYP2D6.
• Consider dose reduction of fluoxetine when using with bupropion 2.

From the Research

Wellbutrin and Fluoxetine Combination

• The combination of Wellbutrin (bupropion) and fluoxetine, an SSRI, has been studied in several clinical trials 3, 4, 5.
• One study found that the combination of bupropion and fluoxetine was effective in relieving depression and accompanying symptoms of anxiety, with a similar safety profile to each medication alone 3.
• However, another study reported a rare case of serotonin syndrome induced by the combination of bupropion and an SSRI, highlighting the potential risk of this combination 6.
• A review of the literature on combining bupropion with SSRIs or SNRIs found that the combination was generally well tolerated and effective in reversing antidepressant-associated sexual dysfunction and boosting antidepressant response 4.
• A pooled analysis of 10 studies found that SSRIs were more effective than bupropion in the treatment of major depressive disorder with high levels of anxiety (anxious depression) 5.

Safety Considerations

• The combination of bupropion and fluoxetine may increase the risk of serotonin syndrome, a potentially fatal complication 6.
• However, the available data suggest that the combination is generally well tolerated, with no statistically significant differences in adverse events compared to each medication alone 3, 4.
• Patients should be closely monitored for signs of serotonin syndrome, such as myoclonic jerks, clumsiness, and gait difficulties, when taking this combination 6.

Efficacy

• The combination of bupropion and fluoxetine may be effective in relieving depression and accompanying symptoms of anxiety 3, 4.
• However, the efficacy of this combination may vary depending on the individual patient and the specific symptoms being treated 5.
• Further studies are needed to fully understand the efficacy and safety of this combination 4.