Individuals with epilepsy are at risk of developing pre-ictal, ictal, postictal or interictal psychoses. Antipsychotic drugs (APDs) are the main class of drugs used to treat psychosis and schizophrenia. The efficacy and safety of APDs as a treatment for epileptic psychosis is not well understood. Hence, we aimed to conduct a systematic review assessing the effectiveness and adverse effects of antipsychotic drugs to treat psychosis in people with epilepsy.

We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched MEDLINE, Embase, PsycInfo and AMED from database inception to 20/06/2023. We contacted experts in the field and performed citation searches to identify additional records. Title, abstract, full-text review, and data analysis were conducted in duplicate, with conflicts resolved by discussion among authors. Given the heterogeneity of study designs, meta-analysis was not deemed appropriate; instead, the results were tabulated in a narrative synthesis. The Joanna Briggs Institute Risk of Bias tool was used to assess study quality.

We identified 13 studies, with a total of 1,180 participants. In the 9 case series included, the psychotic symptoms of all but 3 out of 28 patients treated with APDs partially improved or fully resolved. 3 of the cohort studies reported an association between antipsychotic use and longer duration of psychotic episodes, 2 found similar results in both APD and non-APD groups, and 2 did not report control psychosis outcomes. When reported, seizure frequency was observed to remain unchanged or decrease following APD treatment.

Available evidence does not suggest that antipsychotics increase seizure risk in individuals with epilepsy. However, further data from randomised controlled trials and well-controlled cohort studies are urgently needed to draw more definitive conclusions.