Psychiatric Medications to Avoid in Patients with Seizure History
Patients with a history of seizures should avoid bupropion, clomipramine, maprotiline, chlorpromazine, clozapine, and olanzapine as these medications significantly lower the seizure threshold and increase the risk of seizure recurrence. 1, 2, 3
Antidepressants to Avoid or Use with Caution
High Risk (Avoid)
- Bupropion - significantly lowers seizure threshold and is contraindicated in patients with seizure disorders 4, 3
- Clomipramine - tricyclic antidepressant associated with high seizure risk 3
- Maprotiline - tetracyclic antidepressant with documented seizure risk 3
- Amoxapine - has been associated with increased seizure risk 3
Moderate Risk (Use with Caution)
- SSRIs as a class should be used cautiously in patients with seizure history, with monitoring for seizure activity 1
- Serotonergic medications in combination increase risk of serotonin syndrome, which can include seizures as an advanced symptom 1, 5
Lower Risk Options
- Sertraline, citalopram, and escitalopram appear to have lower seizure risk among SSRIs 3
- Mirtazapine, reboxetine, and venlafaxine are considered relatively safer options 3
Antipsychotics to Avoid or Use with Caution
High Risk (Avoid)
- Chlorpromazine - first-generation antipsychotic with highest seizure risk 2
- Clozapine - second-generation antipsychotic most frequently associated with seizures 2, 6
- Olanzapine - can lower seizure threshold and induce epileptiform discharges 6
Lower Risk Options
- Haloperidol, fluphenazine, pimozide, and trifluoperazine have lower risk of seizure induction 2
- Risperidone appears to confer a relatively low risk among second-generation antipsychotics 2
Risk Factors That Increase Seizure Potential
- Rapid dose titration of psychiatric medications 2, 7
- Concurrent use of multiple medications that lower seizure threshold 2, 7
- History of previous seizure activity 2, 7
- Drug-drug interactions affecting metabolism 4, 7
- Metabolic factors (electrolyte disturbances, hypoglycemia) 7
- Impaired liver or kidney function 7
Medication Management Strategies
- When psychiatric medication is necessary, select agents with lower seizure risk 3
- Start with low doses and titrate slowly 1, 7
- Monitor for early signs of seizure activity 1
- Avoid combining multiple medications that lower seizure threshold 1, 5
- Consider discontinuing medications if seizures occur during treatment 7
- Whenever possible, discontinue all medications, particularly psychotropics, while a patient is receiving ECT 1
Special Considerations
- Lithium should be avoided during ECT due to reports of acute brain syndrome when combined 1
- Carbamazepine, valproate, lamotrigine, gabapentin, and pregabalin may have dual benefit for both seizure control and psychiatric symptoms 3
- Benzodiazepines may increase seizure threshold and can be useful adjuncts in patients requiring psychiatric medication with seizure history 7
- Women with epilepsy should avoid valproic acid if possible and use antiepileptic drug monotherapy at minimum effective dose 1
Monitoring Recommendations
- Regular monitoring of drug levels when applicable 7
- Monitoring of electrolytes, liver function, and other metabolic parameters 7
- EEG monitoring may be considered in high-risk patients starting new psychiatric medications 6
- Close observation during the initial treatment period and after dose increases 1, 7
Remember that the risk of medication-induced seizures must be balanced against the need for effective psychiatric treatment. When psychiatric medications are necessary in patients with seizure history, choosing agents with lower seizure risk, careful dosing, and appropriate monitoring can help minimize risk.