What medications are contraindicated in patients with a history of seizures?

Medications Contraindicated in Absent Seizures

Medications that lower seizure threshold or worsen absence seizures should be avoided in patients with a history of absence seizures, particularly carbamazepine, phenytoin, and certain antipsychotics like chlorpromazine and clozapine. 1, 2

Antiepileptic Drugs Contraindicated in Absence Seizures

Carbamazepine and Phenytoin

• These medications are effective for partial and generalized tonic-clonic seizures but can worsen or precipitate absence seizures
• They may increase the frequency and duration of absence seizures by enhancing GABA-mediated inhibition 2
• Should be avoided as first-line therapy in patients with absence seizures or syndromes where absences are a component (e.g., childhood absence epilepsy, juvenile myoclonic epilepsy)

Phenobarbital

• While sometimes used for seizure management, phenobarbital may be less effective for absence seizures compared to first-line treatments like ethosuximide and valproic acid 2
• Should be used with caution in patients with pure absence seizures

Gabapentin and Pregabalin

• These medications have limited efficacy in absence seizures and may occasionally exacerbate them
• Better alternatives exist for treating absence seizures

Preferred Treatment Options for Absence Seizures

For context, the preferred treatments for absence seizures include:

• Ethosuximide: First-line therapy for pure absence seizures (controls approximately 70% of absences) 2
• Valproic acid: Effective for absence seizures and other generalized seizures (controls absences in 75% of patients) 2
• Lamotrigine: Alternative option, particularly when added to valproic acid for resistant cases 2

Psychotropic Medications to Avoid

Antipsychotics

• Chlorpromazine: High seizurogenic potential, should be avoided 3, 4
• Clozapine: Significantly lowers seizure threshold, with dose-dependent risk 3, 4
• Other antipsychotics with moderate risk: Olanzapine, quetiapine
• Lower-risk alternatives: Haloperidol, fluphenazine, pimozide, risperidone 3, 4

Antidepressants

• Maprotiline and clomipramine: High seizurogenic potential 3, 5
• Bupropion: Known to lower seizure threshold, particularly at higher doses 6
• Lower-risk alternatives: SSRIs like fluoxetine, paroxetine, sertraline; SNRIs like venlafaxine 3, 5

Other Medications with Seizure Risk

Antimicrobials

• Certain fluoroquinolones: Ciprofloxacin, levofloxacin
• Isoniazid: Particularly at higher doses or with pyridoxine deficiency

Stimulants and Sympathomimetics

• Amphetamines and methylphenidate: Can lower seizure threshold
• Pseudoephedrine and phenylephrine: Use with caution

Analgesics

• Tramadol: Can lower seizure threshold, particularly at higher doses 6
• Meperidine: Higher seizure risk compared to other opioids

Risk Factors That Increase Medication-Induced Seizure Risk

Several factors can increase the risk of medication-induced seizures:

• History of epilepsy or seizures: Significantly increases risk 3
• Brain injury or structural abnormalities: Lower baseline seizure threshold
• Renal or hepatic impairment: May lead to drug accumulation
• Polypharmacy: Especially combinations of medications that lower seizure threshold
• Rapid dose titration: Gradual titration is preferred 6
• Electrolyte abnormalities: Particularly hyponatremia, hypocalcemia
• Sleep deprivation and alcohol use: Further lower seizure threshold

Practical Recommendations

1. Obtain detailed seizure history before prescribing any medication with seizurogenic potential
2. Review current medications for potential interactions that could lower seizure threshold
3. Start at lower doses and titrate slowly when using medications with seizure risk
4. Monitor for breakthrough seizures when starting new medications
5. Consider EEG monitoring when high-risk medications cannot be avoided
6. Educate patients about potential seizure risk and warning signs

Special Considerations for Specific Clinical Scenarios

Psychiatric Comorbidities

• For patients requiring antipsychotics: Consider risperidone or haloperidol (lower seizure risk) 3, 4
• For patients requiring antidepressants: Consider SSRIs like fluoxetine or sertraline (lower seizure risk) 3, 5

Pain Management

• Avoid tramadol and meperidine 6
• Consider acetaminophen, NSAIDs, or opioids with lower seizure risk

Respiratory Infections

• Avoid fluoroquinolones when possible
• Consider alternative antibiotic classes

Remember that medication selection should always balance the risk of seizure exacerbation against the need to treat other medical conditions effectively. When high-risk medications cannot be avoided, close monitoring and possibly prophylactic adjustment of antiepileptic medication may be necessary.