Bupropion and Fluoxetine Combination Therapy

Safety Considerations

Bupropion carries a 0.1% seizure risk at therapeutic doses, and caution should be exercised when combining with other drugs that lower seizure threshold, such as fluoxetine, in patients with a history of seizure disorders or elevated seizure risk 1, 2
Use low initial doses and titrate gradually when combining bupropion with other medications that lower seizure threshold, to minimize the risk of seizures in patients with a history of seizure disorders or elevated seizure risk 1, 2
Avoid in patients with seizure disorders, brain metastases, or elevated seizure risk, as bupropion can lower the seizure threshold and increase the risk of seizures in these patients 1, 3

Bupropion has a black box warning for suicidal behavior/ideation in patients younger than 24 years with depression, and patients should be closely monitored for signs of suicidal ideation or behavior when initiating bupropion therapy, particularly in patients with a history of depression or suicidal attempts 4, 5, 6
Serious neuropsychiatric adverse events are rarely associated with bupropion, including in patients with mental illness, but patients should be closely monitored for signs of neuropsychiatric adverse events, such as suicidal ideation or behavior, when initiating bupropion therapy 1, 2

Monitor blood pressure and heart rate, as bupropion can cause elevations, particularly in patients with pre-existing hypertension or cardiovascular disease, and patients should be closely monitored for signs of cardiovascular adverse events, such as hypertension or tachycardia, when initiating bupropion therapy 4, 5, 6, 7

Contraindications include uncontrolled hypertension, as bupropion can cause elevations in blood pressure, and patients with uncontrolled hypertension should not be initiated on bupropion therapy until their blood pressure is adequately controlled 7
Contraindications include active seizure disorder or elevated seizure risk, as bupropion can lower the seizure threshold and increase the risk of seizures in these patients, and patients with a history of seizure disorders or elevated seizure risk should be closely monitored for signs of seizures when initiating bupropion therapy 1, 3
Contraindications include concurrent opioid therapy (if using naltrexone-bupropion formulation), as the combination of bupropion and opioids can increase the risk of adverse events, such as seizures or respiratory depression, and patients should not be initiated on bupropion therapy if they are currently taking opioid medications 7
Contraindications include pregnancy or active attempts to conceive, as bupropion can increase the risk of adverse events, such as birth defects or miscarriage, and patients who are pregnant or attempting to conceive should not be initiated on bupropion therapy 4, 5, 6