Antipsychotics and seizures: What are the risks?

Although evidence suggests antipsychotics can induce different types of epileptic seizures, the quality of this evidence is low. Randomized controlled trials are needed to determine which antipsychotics increase seizure risk and whether there is a dose-effect relationship.

Bottom Line

Among second-generation antipsychotics, clozapine appears to increase the risk of clinical seizure the most. Correlations with dosage and/or plasma levels have not been proven. Psychiatrists should be vigilant for pharmacokinetic interactions between antipsychotics and antiepileptics, notably via CYP1A2 and CYP3A4.

Related Resources

• Druschky K, Bleich S, Grohmann R, et al. Seizure rates under treatment with antipsychotic drugs: Data from the AMSP project. World J Biol Psychiatry. 2018;15:1-10.
• Epilepsy Foundation. For professionals: Antipsychotics. https://www.epilepsy.com/learn/professionals/diagnosistreatment/psychotropic-drugs-developmental-disabilities/comorbid-5.

Drug Brand Names

Aripiprazole • Abilify
Benztropine • Cogentin
Bethanechol • Duvoid
Carbamazepine • Carbatrol, Tegretol
Chlorpromazine • Thorazine
Cimetidine • Tagamet
Ciprofloxacin • Cipro
Citalopram • Celexa
Clonazepam • Klonopin
Clozapine • Clozaril
Donepezil • Aricept
Enalapril • Vasotec
Erythromycin • Erythrocin
Escitalopram • Lexapro
Flunitrazepam • Rohypnol
Fluvoxamine • Luvox
Gabapentin • Neurontin
Haloperidol • Haldol
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Metformin • Fortamet, Glucophage
Mirtazapine • Remeron
Nitrofurantoin • Furadantin
Olanzapine • Zyprexa
Paliperidone • Invega
Phenobarbital • Luminal
Phenytoin • Dilantin
Prochlorperazine • Compazine
Procyclidine • Kemadrin
Propranolol • Inderal
Quetiapine • Seroquel
Risperidone • Risperdal
Sertraline • Zoloft
Simvastatin • Zocor
Sulfamethoxazole/trimethoprim • Bactrim, Sulfatrim
Topiramate • Topamax
Trifluoperazine • Stelazine
Valproic acid • Depakene, Depakote
Ziprasidone • Geodon