Can fluoxetine (Prozac) and bupropion (Wellbutrin) be taken together?

From the Guidelines

Fluoxetine (Prozac) and bupropion (Wellbutrin) can be taken together, but this combination should be used with caution and under close medical supervision. This approach, known as combination therapy, may be used when a single antidepressant doesn't adequately relieve symptoms. The medications work through different mechanisms - fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that increases serotonin levels, while bupropion affects dopamine and norepinephrine. This combination may provide broader neurotransmitter coverage and potentially better symptom relief. However, patients should be aware of potential side effects, including increased risk of seizures, elevated blood pressure, anxiety, insomnia, and serotonin syndrome (though rare with this combination) 1.

Key Considerations

• Dosing typically starts with one medication at a standard dose before adding the second, with gradual adjustments based on response and side effects.
• Patients should be closely monitored for increases in suicidal thoughts and behaviors, especially during the first 1 to 2 months of treatment 1.
• The combination of fluoxetine and bupropion may be associated with a lower rate of sexual adverse events compared to other antidepressant combinations 1.
• Regular follow-up appointments are essential to monitor effectiveness and side effects, and patients should never combine these medications without explicit medical direction.

Recommendations

• The American College of Physicians recommends that clinicians 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 1.
• Clinicians should consider the potential benefits and risks of combination therapy and discuss these with patients before initiating treatment.
• Patients should inform all healthcare providers about all medications they're taking to minimize the risk of adverse interactions.

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)

Fluoxetine and bupropion can be taken together, but it may be necessary to decrease the dose of fluoxetine, particularly for drugs with a narrow therapeutic index, as bupropion is a CYP2D6 inhibitor and fluoxetine is a substrate of CYP2D6 2.

• Key considerations:
  • Bupropion inhibits CYP2D6, which can increase concentrations of fluoxetine.
  • Dose reduction of fluoxetine may be necessary when using with bupropion.
  • Monitor for increased adverse effects of fluoxetine when coadministered with bupropion.
• Reference: 2, 2

From the Research

Combination Therapy of Fluoxetine and Bupropion

• The combination of fluoxetine and bupropion has been studied in various clinical trials to assess its efficacy and safety in treating major depressive disorder (MDD) 3, 4, 5, 6.
• A double-blind randomized study published in 2010 found that the combination of fluoxetine and bupropion was more effective than fluoxetine monotherapy in achieving remission in patients with MDD, with a remission rate of 46% compared to 25% for fluoxetine alone 3.
• Another study published in 1991 compared the efficacy and safety of bupropion and fluoxetine in depressed outpatients and found no statistically significant differences between the two treatments, with response rates of 63% for bupropion and 58% for fluoxetine 4.
• The combination of bupropion and selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, has been found to be effective in treating patients with refractory depression, with some studies suggesting that this combination may be more effective than monotherapy 7, 5, 6.
• The safety profile of the combination of fluoxetine and bupropion has been found to be similar to that of each medication alone, with a low incidence of adverse events, including sexual dysfunction, insomnia, anergy, and tremor 4, 5, 6.

Efficacy and Safety

• The efficacy of the combination of fluoxetine and bupropion in achieving remission in patients with MDD has been found to be higher than that of fluoxetine monotherapy 3.
• The combination of bupropion and SSRIs, including fluoxetine, has been found to be effective in reversing antidepressant-associated sexual dysfunction and in treating patients with refractory depression 7, 5, 6.
• The safety profile of the combination of fluoxetine and bupropion has been found to be similar to that of each medication alone, with a low incidence of adverse events 4, 5, 6.

Clinical Implications

• The combination of fluoxetine and bupropion may be a useful treatment option for patients with MDD who have not responded to monotherapy with either medication 3, 5, 6.
• Clinicians should carefully monitor patients for adverse events, including sexual dysfunction, insomnia, anergy, and tremor, when prescribing the combination of fluoxetine and bupropion 4, 5, 6.
• Further studies are needed to determine the optimal dose and duration of treatment with the combination of fluoxetine and bupropion 6.