Can I give Bupropion (Wellbutrin) and Duloxetine (Cymbalta) together?

From the Guidelines

Yes, Wellbutrin (bupropion) and Cymbalta (duloxetine) can be prescribed together, but this combination should only be taken under close medical supervision due to the potential increased risk of side effects, particularly high blood pressure, seizures, and serotonin syndrome. This combination is sometimes used for patients with depression who haven't responded adequately to a single medication. Wellbutrin works primarily on dopamine and norepinephrine neurotransmitters, while Cymbalta affects serotonin and norepinephrine, so they have complementary mechanisms of action 1.

Key Considerations

• The dosages of each medication may need to be adjusted when used together, with common starting doses being Wellbutrin 150 mg daily and Cymbalta 30 mg daily, and possible gradual increases based on response and tolerability.
• It's essential to inform your doctor about all medications you're taking to avoid potential drug interactions and to report any unusual symptoms promptly.
• 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, as advised by the U.S. Food and Drug Administration 1.
• 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.

Mechanism of Action and Potential Benefits

• Wellbutrin and Cymbalta have different mechanisms of action, which may provide a synergistic effect in treating depression.
• Bupropion is associated with a lower rate of sexual adverse events than some other antidepressants, such as fluoxetine or sertraline, whereas duloxetine may have a higher rate of sexual dysfunction 1.
• The combination of these medications may be beneficial for patients who have not responded to a single medication, as recommended by the American College of Physicians 1.

Potential Risks and Side Effects

• The combination of Wellbutrin and Cymbalta may increase the risk of side effects, particularly high blood pressure, seizures, and serotonin syndrome.
• Patients should be closely monitored for increases in suicidal thoughts and behaviors, especially during the first 1 to 2 months of treatment, as advised by the U.S. Food and Drug Administration 1.
• The risk of adverse effects, such as constipation, diarrhea, dizziness, headache, insomnia, nausea, and somnolence, should be discussed with patients before selecting a medication 1.

From the Research

Combination of Wellbutrin and Cymbalta

• The combination of bupropion (Wellbutrin) and duloxetine (Cymbalta) has not been extensively studied, but there are some reports on the combination of bupropion with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) 2, 3.
• Bupropion inhibits noradrenaline and dopamine reuptake with milder effects on serotonergic activity, and its combination with SSRIs or SNRIs may increase the risk of serotonin syndrome, a potentially fatal complication 2.
• A case report described a 62-year-old woman who developed serotonin syndrome after taking bupropion and sertraline, an SSRI, highlighting the potential risk of this combination 2.
• However, a review of the literature on combining bupropion with SSRIs or SNRIs found that this combination can be effective for treating major depressive disorder (MDD) and can help alleviate antidepressant-associated sexual dysfunction 3.

Mechanism of Action

• Duloxetine, the active ingredient in Cymbalta, is a balanced selective serotonin and norepinephrine-reuptake inhibitor, which means it increases the levels of both serotonin and norepinephrine in the brain 4, 5.
• Bupropion, on the other hand, is a norepinephrine-dopamine reuptake inhibitor, which means it increases the levels of norepinephrine and dopamine in the brain.
• The combination of these two medications may increase the risk of serotonin syndrome due to the increased levels of serotonin in the brain 2.

Safety and Efficacy

• The safety and efficacy of combining bupropion and duloxetine have not been extensively studied, but the available data suggest that this combination can be effective for treating MDD 3.
• However, the combination of bupropion and duloxetine may increase the risk of adverse effects, such as serotonin syndrome, and patients should be closely monitored for signs of this condition 2, 6.
• Patients with a history of hypertension or cardiovascular disease should be cautious when taking this combination, as bupropion and duloxetine may increase blood pressure 6.