Safety and Effectiveness of Clozapine in Youth and Young Adults with Neurodevelopmental Disorders and Severe, Treatment-Refractory Irritability and Aggression: A Retrospective Chart Review.

Abstract

Objective: The purpose of this article was to review the safety, tolerability, and effectiveness of clozapine in youth and young adults with autism spectrum disorder (ASD) and/or intellectual disability. Methods: An IRB-approved retrospective chart review of youth and young adults with autism and/or intellectual disability who were prescribed clozapine between January 2012 and June 2020 was completed. Information was collected from 1 year before through 1 year after clozapine initiation related to medications prescribed, hospitalizations, emergency department (ED) visits, and Clinical Global Impressions-Severity and Clinical Global Impressions-Improvement (CGI-I) ratings. Adverse effects and reasons for stopping clozapine were documented. Results: Fifty-eight patients were included in analysis. Forty patients remained on clozapine through June 2020 and 18 did not. Most patients were prescribed clozapine for treatment of irritability. Reasons for stopping clozapine included side effects, continued behavior concerns, difficulty with blood draws, and improvement in symptoms. For those who remained on clozapine for the duration of the review period, the number of hospitalizations and ED presentations for psychiatric concerns or medical concerns potentially related to clozapine significantly decreased in the year following clozapine initiation compared with the year prior (2.13 vs. 3.48, p = 0.010). There was a significant reduction in CGI-I scores from 3.96 to 2.53 (p < 0.001) from clozapine initiation to 1 year later. There was a nonsignificant trend toward reduction in use of multiple antipsychotics simultaneously from time of clozapine initiation to 1 year later in those who remained on clozapine (38.5% vs. 25%, p = 0.232). Conclusions: Use of clozapine for treatment-refractory irritability in youth and young adults with ASD and/or intellectual disability is generally well-tolerated. Observed benefits included a decrease in number of hospitalizations and ED visits and a decrease in CGI-I score in the year after clozapine initiation.