Is burpropion (bupropion) and fluoxetine okay to take together?

From the Guidelines

Combining bupropion and fluoxetine can be considered safe under close medical supervision, but it's crucial to weigh the potential benefits against the increased risk of side effects, particularly seizures and serotonin syndrome, as noted in studies such as 1.

Key Considerations

• Bupropion and fluoxetine work through different mechanisms - bupropion affects dopamine and norepinephrine, while fluoxetine is a selective serotonin reuptake inhibitor (SSRI) 1.
• The combination may provide better symptom relief for depression that hasn't responded adequately to single-medication treatment, but it requires careful monitoring due to potential increased side effects 1.
• Dosing typically starts with one medication at a standard dose before adding the second at a lower dose with gradual increases as tolerated, emphasizing the need for personalized medical guidance 1.
• Individual factors like medical history, other medications, and specific symptoms will determine if this combination is appropriate, highlighting the importance of close supervision 1.

Potential Risks and Benefits

• Increased risk of seizures and serotonin syndrome, a potentially serious condition with symptoms like confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and hyperthermia 1.
• Bupropion is associated with a lower rate of sexual adverse events than fluoxetine, which is an important consideration in treatment selection 1.
• The combination may increase blood levels of bupropion due to fluoxetine's effects on liver enzymes, necessitating careful monitoring of side effects and drug levels 1.

Clinical Guidance

• Never start, adjust, or combine these medications without explicit guidance from your healthcare provider, as the decision to use this combination should be based on a thorough evaluation of the patient's condition and potential risks 1.
• Regular assessment of patient status, therapeutic response, and adverse effects of antidepressant therapy is recommended, beginning within 1 to 2 weeks of initiation of therapy, as advised by the American College of Physicians 1.

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 and fluoxetine can be used 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 can increase the exposure of fluoxetine 2.

From the Research

Combination of Bupropion and Fluoxetine

• The combination of bupropion and fluoxetine is not directly addressed in most of the studies provided, but there is evidence to suggest that bupropion can be used in combination with selective serotonin reuptake inhibitors (SSRIs) like fluoxetine 3.
• One study reported a case of serotonin syndrome induced by a combination of bupropion and an SSRI, highlighting the potential risk of this combination 4.
• However, another study found that the combination of bupropion and an SSRI can be effective in treating major depressive disorder and can help alleviate SSRI-associated sexual dysfunction 3.

Safety and Efficacy

• The safety and efficacy of combining bupropion with fluoxetine are not well established, and more research is needed to fully understand the potential benefits and risks of this combination 3.
• Bupropion has been shown to increase the risk of adverse events, including psychiatric adverse events, and can increase the risk of trial dropout due to adverse events 5.
• Fluoxetine, as an SSRI, has its own set of potential side effects and risks, and the combination of bupropion and fluoxetine may increase the risk of certain adverse events 6, 7.

Clinical Use

• The decision to use bupropion and fluoxetine together should be made on a case-by-case basis, taking into account the individual patient's medical history, current medications, and potential risks and benefits 3.
• Clinicians should carefully monitor patients for signs of serotonin syndrome, adverse events, and other potential risks when using this combination 4, 5.