From the Guidelines
Taking Wellbutrin (bupropion) with fluoxetine is generally considered safe for most people, but this combination should only be used under close medical supervision. These medications can work well together for treating depression, particularly when one medication alone hasn't been effective. The combination may be beneficial because they work through different mechanisms - fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that increases serotonin levels, while Wellbutrin affects dopamine and norepinephrine. However, there are important considerations to be aware of. This combination may slightly increase the risk of seizures, especially at higher doses of Wellbutrin, as well as a small risk of developing serotonin syndrome, a potentially serious condition caused by excessive serotonin levels 1. Side effects might include increased anxiety, insomnia, or elevated blood pressure.
According to the American College of Physicians, when choosing pharmacologic therapy to treat patients with acute major depression, clinicians should select second-generation antidepressants on the basis of adverse effect profiles, cost, and patient preferences 1. Bupropion is associated with a lower rate of sexual adverse events than fluoxetine or sertraline, whereas paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline.
Key considerations when using this combination include:
- Monitoring for increased risk of seizures, especially at higher doses of Wellbutrin
- Watching for signs of serotonin syndrome, such as excessive serotonin levels
- Managing potential side effects, including increased anxiety, insomnia, or elevated blood pressure
- Regular assessment of patient status, therapeutic response, and adverse effects of antidepressant therapy, beginning within 1 to 2 weeks of initiation of therapy 1.
Your doctor will need to monitor you closely, especially when starting this combination or adjusting doses. Never adjust these medications on your own, and be sure to inform your healthcare provider about all other medications you're taking to avoid potential interactions. The most recent and highest quality study on this topic is from 2016, which provides guidance on the nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder 1.
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
Combination of 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 life-threatening condition 3, 4, 5.
- Serotonin syndrome is characterized by symptoms such as mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 5.
- A case study reported a 62-year-old woman who developed serotonin syndrome after taking bupropion and sertraline, an SSRI, for three weeks 3.
- Another case study reported a 24-year-old male who developed delayed-onset serotonin syndrome after ingesting a mixture of fluoxetine, bupropion, and other medications 4.
Safety and Efficacy of Combination Therapy
- Some studies suggest that combining bupropion with SSRIs like fluoxetine can be effective in treating major depressive disorder (MDD) and reversing antidepressant-associated sexual dysfunction 6.
- However, the combination of bupropion and SSRIs is not an approved indication, and more randomized controlled studies are needed to determine the optimal dose and duration of treatment 6.
- The available data suggest that the combination of bupropion and SSRIs is generally well tolerated, but clinicians should be aware of the potential risks of serotonin syndrome 3, 4, 5, 6.
Precautions and Monitoring
- Clinicians should carefully monitor patients who are taking bupropion and fluoxetine concurrently for signs of serotonin syndrome, such as mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 5.
- Patients should be educated about the potential risks of serotonin syndrome and the importance of seeking medical attention immediately if they experience any symptoms 5.