What drugs can trigger epilepsy? A guide to pharmacologically-induced seizures

October 11, 2025 •

2 min read

Over 5% of all cases of status epilepticus—a dangerous, prolonged seizure—are caused by a drug or poison, highlighting the significant link between substances and seizure activity. This guide explores what drugs can trigger epilepsy and seizures, and the factors that increase a person's risk.

Quick Summary

Many common prescription, illicit, and over-the-counter drugs can lower the seizure threshold in susceptible individuals. Risk factors include dosage, patient health, and drug interactions.

Key Points

Bupropion: The antidepressant bupropion is a commonly reported cause of drug-induced seizures, especially at high doses or with certain formulations.
Tramadol: This opioid analgesic can trigger seizures even at therapeutic doses, with the risk rising sharply with overdose or specific drug combinations.
Antibiotics and Seizures: Certain antibiotics, particularly imipenem and some penicillins or cephalosporins, can lower the seizure threshold, especially with poor kidney function.
Withdrawal Is a Risk: Abruptly stopping chronic use of sedatives like benzodiazepines, barbiturates, or alcohol is a significant and life-threatening cause of seizures.
Risk Factors Matter: An individual's risk for drug-induced seizures increases with higher drug doses, impaired kidney/liver function, and a pre-existing history of epilepsy.
Illicit Drugs are High-Risk: Stimulants like cocaine, amphetamines, and synthetic cannabinoids are known to cause seizures through direct CNS overstimulation.

How Medications and Substances Affect Seizure Threshold

Certain drugs can disrupt the delicate balance of neurotransmitters in the brain, particularly the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurotransmitter glutamate. An imbalance in this system can cause hyperexcitability in the brain, leading to a seizure. The mechanisms include disrupting GABA or glutamate, withdrawal from CNS depressants, or toxic accumulation due to organ dysfunction. For more detailed information on these mechanisms and the specific drug classes associated with seizures, {Link: Dr.Oracle https://www.droracle.ai/articles/88538/tramadol-seizure}.

Antidepressants and Antipsychotics

Some psychiatric medications can increase seizure risk, often in a dose-dependent manner. Commonly implicated drugs include bupropion, older tricyclic antidepressants (TCAs), and the antipsychotic clozapine. Other second-generation antipsychotics also pose a seizure risk.

Antibiotics

Certain antibiotics can trigger seizures, often with high doses, underlying kidney/CNS issues, or pre-existing epilepsy. Beta-lactam antibiotics, fluoroquinolones, and isoniazid have been linked to seizures.

Pain Medications

Tramadol can induce seizures even at therapeutic doses. Overdose of certain NSAIDs has also been linked to seizures.

Withdrawal and Recreational Drugs

Withdrawal from alcohol, benzodiazepines or barbiturates can cause seizures. Illicit stimulants like cocaine, amphetamines, and synthetic cannabinoids are also known causes.

Over-the-Counter Drugs

Overdose of certain OTC medications can trigger seizures, including some antihistamines and decongestants.

Risk Factors and Prevention Strategies

Factors increasing susceptibility include pre-existing epilepsy, high doses, impaired organ function, and drug interactions. Prevention involves careful medication management and, when necessary, medically supervised withdrawal. A table summarizing drug classes, examples, mechanisms, and risk factors can be found on {Link: Dr.Oracle https://www.droracle.ai/articles/88538/tramadol-seizure}.

Conclusion

Awareness of potential seizure triggers from various substances is vital. Risk factors include certain prescription medications, withdrawal, illicit drugs, high doses, and patient health. Understanding these risks and managing factors like kidney function and drug interactions is crucial. Always consult a healthcare provider about medications, especially with a history of epilepsy. Additional resources are available from the Epilepsy Foundation.

Frequently Asked Questions

Yes, some antidepressants can increase the risk of seizures, even at therapeutic doses. Bupropion and older tricyclic antidepressants (TCAs) are particularly known for this risk, which is often dose-dependent.

Tramadol should be used with extreme caution or avoided entirely in patients with a history of seizures or epilepsy. The drug lowers the seizure threshold, and the risk increases with higher doses or when combined with other drugs like antidepressants.

Abrupt cessation of benzodiazepines after chronic use can lead to life-threatening withdrawal seizures. A medically supervised, slow dose taper is necessary to minimize this risk.

No, not all antibiotics carry a significant seizure risk, but several classes do, most notably beta-lactams (e.g., penicillins, cephalosporins, carbapenems) and fluoroquinolones. The risk is highest with high doses, renal dysfunction, or pre-existing CNS issues.

Yes, drug-drug interactions are a significant risk factor. For example, combining Tramadol with other serotonergic agents like antidepressants can increase the risk of both serotonin syndrome and seizures. Co-prescribing medications that both lower the seizure threshold can be especially dangerous.

Yes, some over-the-counter medications can trigger seizures, especially in overdose. These include certain antihistamines (like diphenhydramine) and decongestants (like pseudoephedrine) that act as CNS stimulants.

Illicit stimulants like cocaine and amphetamines can trigger seizures by over-exciting the central nervous system. This direct stimulation can overwhelm the brain's inhibitory mechanisms and lead to seizure activity.