From the Guidelines
Wellbutrin (bupropion) can lower the seizure threshold, increasing the risk of seizures in some patients, and should be avoided in patients with epilepsy and used with caution in patients with a history of seizures or with clinical factors that may increase the risk of seizures. The risk is dose-dependent, with higher doses carrying greater seizure risk. For immediate-release Wellbutrin, doses should not exceed 450 mg/day, with single doses limited to 150 mg. For sustained-release formulations, the maximum daily dose is 400 mg, given as 200 mg twice daily. For extended-release (XL), the maximum is 450 mg once daily. Patients with certain conditions face higher seizure risks, including those with a history of seizures, head trauma, CNS tumors, severe liver disease, eating disorders, or those undergoing alcohol or benzodiazepine withdrawal. Combining Wellbutrin with other medications that lower seizure threshold (such as antipsychotics, antidepressants, stimulants, or systemic steroids) further increases risk, as noted in studies such as 1. The seizure risk occurs because bupropion and its metabolites inhibit neuronal reuptake of dopamine and norepinephrine while also affecting acetylcholine, serotonin, and histamine systems, potentially leading to neuronal hyperexcitability.
Some key points to consider when prescribing Wellbutrin include:
- Starting patients on low doses with gradual increases to minimize the risk of seizures
- Avoiding the use of Wellbutrin in patients with epilepsy, as stated in 1
- Using caution when prescribing Wellbutrin to patients with a history of seizures or with clinical factors that may increase the risk of seizures
- Monitoring patients for signs of seizure activity, such as changes in behavior or neurological symptoms
- Considering alternative medications for patients with risk factors for seizures, as suggested by studies such as 1
It is essential to weigh the benefits of using Wellbutrin against the potential risks, particularly in patients with a history of seizures or other risk factors. By taking a cautious approach and carefully monitoring patients, healthcare providers can minimize the risk of seizures and ensure the safe use of Wellbutrin. According to 1, bupropion may lower the seizure threshold, and naltrexone-bupropion ER should be avoided in patients with epilepsy and should be used with caution in patients with a history of seizures or with clinical factors that may increase the risk of seizures.
From the FDA Drug Label
The risk of seizures is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients with a seizure disorder or conditions that increase the risk of seizure (e.g., severe head injury, arteriovenous malformation, CNS tumor or CNS infection, severe stroke, anorexia nervosa or bulimia, or abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Contraindications (4)]. The following conditions can also increase the risk of seizure: concomitant use of other medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids), metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia), or use of illicit drugs (e.g., cocaine) or abuse or misuse of prescription drugs such as CNS stimulants.
Bupropion and Seizure Threshold: Bupropion can cause seizures, and the risk is dose-related. The dose should not exceed 300 mg once daily, and the risk of seizures is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold.
- Key factors that increase the risk of seizure:
- Concomitant use of other medications that lower the seizure threshold
- Metabolic disorders
- Use of illicit drugs or abuse/misuse of prescription drugs
- Certain medical conditions, such as severe head injury or CNS tumor The incidence of seizure with bupropion hydrochloride extended-release tablets (XL) has not been formally evaluated in clinical trials, but studies using bupropion HCl sustained-release suggest that the estimated seizure incidence increases almost tenfold between 450 and 600 mg/day 2.
From the Research
Wellbutrin Seizure Threshold
- Bupropion, also known as Wellbutrin, has been associated with a reduced seizure threshold, particularly at high doses or in patients with a history of seizure disorders 3, 4, 5, 6, 7.
- Studies have shown that the risk of seizures with bupropion is higher at doses above the recommended maximum, and predisposing factors such as a personal or family history of seizures can increase this risk 4, 5, 6, 7.
- The incidence of seizures with bupropion has been reported to be around 0.35%-0.44% at doses of 450 mg/day or less, and the cumulative 2-year risk of seizures at this dose is approximately 0.48% 7.
- Bupropion is contraindicated in patients with a known history of seizures, and its use should be approached with caution in patients with other risk factors for seizures 3, 4, 6.
- In patients without a history of seizures, the risk of new-onset seizures with bupropion is still present, although it is considered rare 4, 5, 6.
Risk Factors
- Personal or family history of seizure disorders 4, 5, 6, 7
- High doses of bupropion 3, 4, 5, 6, 7
- Other predisposing factors such as discontinuation of certain medications, e.g. alprazolam 4
- Presence of other neurological or organic illnesses 5
Recommendations
- Bupropion should be used with caution in patients with risk factors for seizures 3, 4, 6
- Patients should be monitored for signs of seizures, particularly when starting or increasing the dose of bupropion 4, 5, 6
- Alternative treatments should be considered for patients with a history of seizures or other risk factors 3, 4, 6