Tuberous sclerosis-associated psychosis: a systematic review

A variety of neuropsychiatric symptoms have been reported in tuberous sclerosis. Although psychosis may occur, little has been written about this topic. This systematic review sought to characterize the nature of tuberous sclerosis-associated psychosis, including with respect to treatment response. A literature search was completed in June 2025 using PubMed and Scopus. Only articles that mentioned psychotic symptoms occurring in tuberous sclerosis in a patient-specific manner were eligible. Twenty-six papers describing 27 individuals were included in the main analyses, all of which are case reports. The average age of psychosis onset and types of psychotic symptoms experienced by the individuals included in the review were similar to that seen in schizophrenia. Although the majority of individuals had a history of seizures, including 10 who experienced residual seizures, psychotic symptoms were believed to be seizure-related in only three cases. Only eight individuals were explicitly noted to have an intellectual disability and only one possibly had autism. Among individuals for whom information pertaining to treatment response was available, 75% exhibited a good response to at least one antipsychotic trial, whereas only 12.5% each responded partially or poorly. Side effects were noted in only five cases. These results suggest that psychotic presentations in tuberous sclerosis can resemble schizophrenia and that antipsychotic therapy may be reasonably effective and well tolerated in affected individuals. However, this review had numerous limitations that prevent firm conclusions from being drawn (in particular, the absence of any randomized controlled trials), underscoring the need for more reports to be published.