Can bupropion (Bupropion) and sertraline (Sertraline) be given together?

From the Guidelines

Bupropion and sertraline can be safely prescribed together, and this combination is sometimes used in clinical practice. This approach, known as combination antidepressant therapy, may be beneficial for patients who haven't responded adequately to a single antidepressant. The medications work through different mechanisms - sertraline is a selective serotonin reuptake inhibitor (SSRI) that increases serotonin levels, while bupropion affects dopamine and norepinephrine systems. This complementary action can provide broader neurotransmitter coverage and potentially better symptom relief, particularly when depression is accompanied by fatigue or lack of motivation.

Key Considerations

• When starting this combination, it's typically recommended to begin with one medication, stabilize the dose, then add the second medication gradually.
• Patients should be monitored for potential side effects, including increased anxiety, insomnia, or blood pressure changes.
• While the risk of serotonin syndrome is lower with this particular combination compared to combining two serotonergic agents, patients should still be aware of symptoms like confusion, rapid heart rate, dilated pupils, or muscle rigidity, which would require immediate medical attention.

Evidence Base

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.

Monitoring and Adjustments

• Regular monitoring for suicidal thoughts and behaviors is advised, particularly in the first 1 to 2 months of treatment 1.
• Treatment should be modified if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder 1.

Side Effects and Risks

• Bupropion is associated with a lower rate of sexual adverse events than fluoxetine or sertraline 1.
• SSRIs, including sertraline, are associated with an increased risk for suicide attempts compared with placebo 1.
• The combination of bupropion and sertraline may have a lower risk of serotonin syndrome compared to combining two serotonergic agents, but patients should still be aware of the symptoms 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 sertraline can be given together, but it may be necessary to decrease the dose of sertraline, as bupropion is a CYP2D6 inhibitor and sertraline is a substrate of CYP2D6.

• Monitor the patient closely for increased exposures of sertraline and adjust the dose as necessary.
• Use low initial doses and increase the dose gradually to minimize the risk of adverse reactions.
• Refer to the clinical pharmacology section for more information on drug interactions 2.

From the Research

Combination of Bupropion and Sertraline

• The combination of bupropion and sertraline has been studied in various clinical settings, with some studies suggesting that it can be effective for treating depression, particularly in patients who have not responded to monotherapy 3, 4, 5.
• However, there is also a risk of serotonin syndrome, a potentially fatal complication, when combining bupropion with selective serotonin reuptake inhibitors (SSRIs) like sertraline 6.
• A study published in 2004 reported a case of serotonin syndrome in a patient taking bupropion and sertraline, highlighting the need for careful monitoring when combining these medications 6.
• Other studies have found that the combination of bupropion and sertraline can be safe and effective, with some patients experiencing improved symptoms and reduced sexual side effects compared to monotherapy 3, 4, 5.
• A review of the literature on combining bupropion with SSRIs or SNRIs found that the available data suggest that this combination is generally well tolerated and can boost antidepressant response, although more randomized controlled studies are needed to answer important questions about optimal dose and duration of treatment 5.
• A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline found that both medications were effective in treating depression, but sertraline was more often associated with sexual dysfunction and certain other adverse events compared to bupropion SR 7.

Key Findings

• The combination of bupropion and sertraline can be effective for treating depression, but it also carries a risk of serotonin syndrome 6, 3, 4, 5.
• Careful monitoring is necessary when combining these medications to minimize the risk of adverse effects 6.
• The combination of bupropion and sertraline may be a useful option for patients who have not responded to monotherapy, but more research is needed to fully understand its safety and efficacy 3, 4, 5.