Can medications such as antidepressants (e.g. bupropion), antipsychotics (e.g. clozapine), and antibiotics (e.g. ciprofloxacin) provoke seizures in patients with a history of seizure disorders?

Medications That Can Provoke Seizures

Yes, multiple commonly prescribed medications can provoke seizures, with bupropion, clozapine, and certain antibiotics like fluoroquinolones being among the highest risk agents that should be avoided or used with extreme caution in patients with seizure history. 1, 2

High-Risk Medications by Class

Antidepressants

• Bupropion carries the highest seizure risk among antidepressants, with an incidence of approximately 0.4% at recommended doses (300 mg/day) and nearly 1/1000 patients at this dose 1, 3, 4
• The FDA explicitly contraindicates bupropion in patients with seizure disorders, and the risk increases almost tenfold between 450-600 mg/day 1
• Bupropion should be introduced with care in patients with seizure history and discontinued immediately if seizure occurs 1
• Safer alternatives include fluoxetine, sertraline, and fluvoxamine, which have lower seizure risk (0.1-0.2% in clinical trials) 5, 6, 3
• Tricyclic antidepressants (particularly imipramine) carry intermediate risk at 0.3-0.6% at effective doses 3

Antipsychotics

• Clozapine has the highest seizure risk among antipsychotics, with an estimated cumulative seizure risk of 10% in patients treated for 3.8 years 2, 7
• The risk with clozapine is dose-dependent and increases with rapid titration 2
• First-generation antipsychotics: chlorpromazine carries the greatest risk, while haloperidol, fluphenazine, pimozide, and trifluoperazine have lower risk 2
• Second-generation antipsychotics: risperidone confers relatively low risk compared to clozapine 2
• Cariprazine (Vraylar) requires careful monitoring in patients with seizure history, with initiation at the lowest dose (1.5 mg/day) and ensuring adequate seizure control before starting 8

Antibiotics

• Fluoroquinolones (including ciprofloxacin) can provoke seizures, particularly in patients with pre-existing seizure disorders 9
• The mechanism involves lowering the seizure threshold through CNS effects 9
• Approximately 6.1% of first-occurring seizures are drug-induced, with antibiotics being a significant contributor 9

Other High-Risk Medications

• Theophylline and systemic corticosteroids lower seizure threshold 1
• CNS stimulants and certain analgesics carry seizure risk 1, 9
• Immunosuppressants and antitumor agents are associated with drug-induced seizures 9

Critical Risk Factors That Amplify Seizure Risk

Patient-Specific Factors

• History of seizures or epilepsy is the strongest predictor 1, 9
• Severe head injury, arteriovenous malformation, CNS tumor, CNS infection, or severe stroke 1
• Metabolic disorders: hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia 1
• Diabetes mellitus treated with oral hypoglycemics or insulin 1
• Elderly patients and children are at higher risk 9
• Impaired liver or kidney function affecting drug metabolism and excretion 9

Medication-Related Factors

• Polypharmacy with multiple seizure-threshold-lowering drugs creates additive or potentially synergistic risk 7, 9
• The combination of bupropion and clozapine is particularly dangerous, with case reports of seizures even without prior seizure history 7
• Rapid dose titration increases risk 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1

Management Approach for Patients with Seizure History

Pre-Treatment Assessment

• Ensure adequate seizure control with anticonvulsants before initiating any seizure-risk medication 5, 8
• Verify stable seizure control and appropriate anticonvulsant regimen 8
• Consider baseline EEG if seizure control is uncertain 8
• Maintain communication with the patient's neurologist 8

Medication Selection Strategy

• Choose alternative medications with lower seizure risk whenever possible 5, 7
• For antidepressants: prefer fluoxetine, sertraline, or fluvoxamine over bupropion 5
• For antipsychotics: avoid clozapine if alternatives are viable 2, 7
• Oseltamivir is safe and has no documented association with increased seizure activity, unlike older influenza antivirals (amantadine, rimantadine) 10

Dosing Strategy

• Use "start low, go slow" approach with gradual titration 5, 8
• Initiate at the lowest effective dose 5, 8
• For bupropion specifically: never exceed 300 mg once daily 1
• Avoid combining multiple medications that lower seizure threshold 8

Monitoring Protocol

• Monitor closely for breakthrough seizure activity during initiation and dose adjustments 5, 8
• Educate patients and caregivers on recognizing seizure activity 8
• Monitor serum drug levels when applicable 9
• Track metabolic parameters (liver enzymes, electrolytes, glucose) 9

Critical Pitfalls to Avoid

• Never start seizure-risk medications if seizures are poorly controlled or if recent breakthrough seizures have occurred 8
• Do not combine bupropion with clozapine due to potentially synergistic seizure risk 7
• Avoid enzyme-inducing anticonvulsants that may interact with drug metabolism; prefer levetiracetam or lamotrigine 8
• Discontinue the offending medication immediately if seizure occurs and do not restart 1
• Do not ignore metabolic factors or drug-drug interactions that compound risk 2, 9

Emergency Management

• For drug-induced status epilepticus: benzodiazepines are first-line treatment 11, 9
• Second-line agents include barbiturates and propofol 11, 9
• Additional anticonvulsants (phenytoin, fosphenytoin, valproate, levetiracetam) may be needed for refractory cases 11