Background: Psychotic symptoms in multiple sclerosis (MS) have been infrequently studied, despite the existence of numerous case reports showing inconsistent findings. Our aim was to assess the timing of psychosis onset and examine its characteristics in MS cases.

Methods: We conducted a systematic review and meta-analysis according to PRISMA 2020. We searched for case reports and case series of psychosis in MS on MEDLINE through PubMed, Google Scholar, Web of Science, and Cochrane. SPSS 26 was used to perform the data analysis.

Results: Overall, 43 cases were reviewed. Bipolar disorder and schizophrenia (SCZ) were the most frequently observed types. Psychosis was often present before or at the time of MS diagnosis. For patients with prior psychosis before MS diagnosis, those with SCZ were less likely to develop neurologic symptoms compared to those with other psychosis types. Polymorphic delusions were significantly associated with psychosis onset either after or concurrently with MS. Extensive periventricular white matter lesions, cerebellar peduncles, and cerebellar lesions were significantly associated with the onset of psychosis following MS diagnosis. Resistant-treatment psychosis occurred in 59.4% of cases. A favorable outcome was significantly more common in patients with relapsing-remitting MS compared to those with other forms of MS.

Conclusions: Our study highlights the importance of considering MS in patients with psychoses, especially those with SCZ or treatment-resistant psychosis. Some white matter lesions may trigger psychosis after MS diagnosis. While managing psychosis in MS can be challenging, MS-specific treatments have proven effective.