Clozapine Use Among Individuals With Schizophrenia Occurring on the Background of Intellectual Disability and Rare Genetic Variation: A Retrospective Chart Review.

Abstract

Background: Treatment resistance in schizophrenia is associated with both intellectual disability and rare genetic variation. Information pertaining to the use of clozapine in this context has primarily come from case reports and small case series. Given the frequent occurrence of comorbid medical issues in various genetic disorders and the heightened sensitivity to antipsychotic medications among intellectually disabled individuals, additional information regarding the effectiveness and tolerability of clozapine in this population is needed, particularly in light of its unique side effect profile.

Methods: This retrospective review of 1200 charts, which took place at a subspecialty psychiatry clinic, sought to characterize the use of clozapine in individuals with schizophrenia (or psychotic symptoms, generally speaking) and intellectual disability occurring on the background of rare genetic variation, a difficult to study and underserved patient population.

Results: Twelve hundred charts were reviewed and 10 eligible individuals were identified, all of whom had been prescribed clozapine and carried a diagnosis of schizophrenia on the background of intellectual disability and rare genetic variation. Six of these 10 individuals harbored presumed pathogenic variants.

Implications: This study affirms what is known about clozapine treatment in 22q11.2 deletion syndrome, adds to the scarce literature on Usher syndrome in this context, and provides the first accounts of clozapine use in 22q11.2 microduplication syndrome and DCX variant-related heterotopia.