Psychotic disorders represent a relatively rare but serious comorbidity in epilepsy. Current epidemiological studies are showing a point prevalence of 5.6% in unselected samples of people with epilepsy going up to 7% in patients with temporal lobe epilepsy, with a pooled odds ratio of 7.8 as compared with the general population. This is a narrative review of the most recent updates in the management of psychotic disorders in epilepsy, taking into account the clinical scenarios where psychotic symptoms occur in epilepsy, interactions with antiepileptic drugs (AEDs) and the risk of seizures with antipsychotics. Psychotic symptoms in epilepsy can arise in a number of different clinical scenarios from peri-ictal symptoms, to chronic interictal psychoses, comorbid schizophrenia and related disorders to the so-called forced normalization phenomenon. Data on the treatment of psychotic disorders in epilepsy are still limited and the management of these problems is still based on individual clinical experience. For this reason, guidelines of treatment outside epilepsy should be adopted taking into account epilepsy-related issues including interactions with AEDs and seizure risk. Second-generation antipsychotics, especially risperidone, can represent a reasonable first-line option because of the low propensity for drug–drug interactions and the low risk of seizures. Quetiapine is burdened by a clinically significant pharmacokinetic interaction with enzyme-inducing drugs leading to undetectable levels of the antipsychotic, even for dosages up to 700 mg per day.
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