From the Guidelines
Medications that lower the seizure threshold include bupropion, antipsychotics (particularly clozapine, chlorpromazine, and olanzapine), antidepressants (especially tricyclics like amitriptyline, and SSRIs at high doses), stimulants (methylphenidate, amphetamines), antibiotics (carbapenems, quinolones, isoniazid), analgesics (tramadol, meperidine), and certain anesthetics (propofol, etomidate) as noted in studies 1.
Key Medications
- Bupropion, an antidepressant, has been shown to reduce the seizure threshold, with a 0.1% seizure risk among those receiving the drug for smoking cessation 1.
- Antipsychotics, such as clozapine, chlorpromazine, and olanzapine, can lower the seizure threshold in a dose-dependent manner, with clozapine having a 5% incidence of seizures at high dosages 1.
- Stimulants, including methylphenidate and amphetamines, can also lower the seizure threshold by altering neurotransmitter balance and changing neuronal excitability.
- Certain antibiotics, such as carbapenems, quinolones, and isoniazid, have been reported to lower the seizure threshold, particularly in patients with a history of seizures or epilepsy.
- Analgesics like tramadol and meperidine can also affect seizure threshold, and their use should be cautious in at-risk patients.
Mechanism and Patient Risk
These medications affect seizure threshold through various mechanisms, including altering neurotransmitter balance (particularly GABA and glutamate), changing neuronal excitability, or interfering with ion channels 1. Patients with epilepsy, history of seizures, brain injury, or other neurological conditions are at higher risk when taking these medications, and prescribing these drugs to at-risk patients should be done with caution, considering starting at lower doses, titrating slowly, monitoring closely, and avoiding combinations of multiple threshold-lowering medications.
Clinical Considerations
In some cases, prophylactic anticonvulsant therapy might be warranted when these medications cannot be avoided in high-risk individuals, as noted in the management of adult patients presenting to the emergency department with seizures 1. It is essential to consider the potential risks and benefits of these medications and to closely monitor patients for signs of seizure activity or other adverse effects.
From the FDA Drug Label
• Drugs that lower seizure threshold: Dose bupropion hydrochloride extended-release tablets (XL) with caution. ( 5.3,7.3) Bupropion is a medication that lowers the seizure threshold.
- Key consideration: Dose bupropion with caution when used with other drugs that lower the seizure threshold 2.
From the Research
Medication that Lowers the Seizure Threshold
- Bupropion is a medication that can lower the seizure threshold, with an incidence of seizure at 300 mg per day of 1/1000 patients treated 3, 4.
- Tricyclic antidepressants, such as clomipramine and amoxapine, can also lower the seizure threshold and are not recommended for patients with epilepsy 5, 6.
- Other medications that can lower the seizure threshold include maprotiline 5.
- Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs), such as sertraline, citalopram, and fluoxetine, are generally considered safe for patients with epilepsy and may even have a protective effect against seizures 7, 5, 6.
Medications to Avoid in Patients with Epilepsy
- Bupropion should be avoided in patients with epilepsy due to its potential to lower the seizure threshold 3, 5, 4.
- Tricyclic antidepressants, such as clomipramine and amoxapine, should also be avoided in patients with epilepsy 5, 6.
- Maprotiline should be avoided in patients with epilepsy due to its potential to lower the seizure threshold 5.