Is Contrave (bupropion) safe to use in patients with a history of absence seizures?

Contrave (Naltrexone/Bupropion) is Contraindicated in Patients with Absence Seizures

Contrave (naltrexone/bupropion) is absolutely contraindicated in patients with a history of absence seizures or any seizure disorder due to bupropion's known ability to lower the seizure threshold. 1, 2

Mechanism and Seizure Risk

Contrave contains bupropion, which is a dopamine and norepinephrine reuptake inhibitor that significantly lowers the seizure threshold. The FDA label and clinical guidelines explicitly state that bupropion-containing medications should be avoided in patients with:

• Any seizure disorder, including absence seizures
• Conditions that increase seizure risk
• History of seizures 1, 2

The seizure risk with bupropion is dose-dependent, with studies showing:

• 0.1% incidence with sustained-release formulations up to 300 mg daily
• 0.4% with immediate-release formulations at 300-450 mg daily
• Nearly tenfold increase in risk between 450-600 mg daily 1

Contraindications for Contrave

Contrave is specifically contraindicated in:

• Patients with seizure disorders of any type
• Patients taking medications that lower seizure threshold
• Patients with conditions that predispose to seizures 2

Alternative Weight Management Options

For patients with absence seizures who require pharmacotherapy for obesity, safer alternatives include:

1. Orlistat (Xenical): Works through a peripheral mechanism as a lipase inhibitor with no known effects on seizure threshold 2

2. Lorcaserin (Belviq): A 5-HT2C receptor agonist that is specifically noted as a safer alternative for patients with cardiovascular disease and would also be safer for those with seizure disorders 2

3. Liraglutide (Saxenda): A GLP-1 analog administered by subcutaneous injection with no known effects on seizure threshold 2

Clinical Considerations

The risk of seizures with bupropion is not theoretical. Multiple case reports document seizures occurring in patients without prior seizure history when taking bupropion, even at therapeutic doses 3, 4, 5. This risk would be substantially higher in someone with a pre-existing seizure disorder like absence seizures.

Even in patients without a seizure history, the observed seizure rate with therapeutic bupropion use ranges from 0.06% to 0.15% 5, and this risk would be magnified in those with a history of seizures.

Important Warnings

• The combination of bupropion with other medications that lower seizure threshold can have additive or potentially synergistic effects on seizure risk 6
• Patients with absence seizures already have abnormal brain electrical activity, making them particularly vulnerable to medications that further reduce seizure threshold
• The risk of seizure with bupropion appears higher with doses above the recommended maximum, but seizures have occurred even at therapeutic doses 7

In conclusion, the risk of triggering or worsening seizures in a patient with absence seizures far outweighs any potential benefits of Contrave for weight management, especially when safer alternatives are available.