title: Clozapine for Drug-Refractory Irritability in Individuals with Developmental Disability.
abstract: In this case series, we describe the acute clinical impact and tolerability of rapid titration of clozapine for treatment of refractory irritability in five hospitalized youth with developmental disability. We offer this descriptive report in an effort to expand the evidence base guiding treatment of refractory aggression in this population.
  
  
  
  Five youth with developmental disability and severe irritability were admitted to a 10-bed psychiatric crisis stabilization unit where they received thorough psychiatric and medical evaluation. Informed consent was obtained in each case, and each patient underwent rapid titration onto clozapine. Clozapine monitoring guidelines were followed for all patients throughout treatment, and clinical severity at baseline and improvement with treatment was measured by use of the Clinical Global Impressions-Severity scale (CGI-S) and the Clinical Global Impressions-Improvement scale (CGI-I).
  
  
  
  One female and four males diagnosed with developmental disability and at least one other psychiatric diagnosis, mean age of 13.1 ± 2.1 years, and mean CGI-S at baseline of 5.8, each received clozapine treatment by rapid titration. The mean therapeutic total daily dose of clozapine was 380 ± 200 mg. All patients demonstrated acute clinical improvement with the mean final CGI-I of 2.0, or "much improved."
  
  
  
  These initial results support the potential utility of clozapine rapid titration for treatment of severe refractory irritability in youth with developmental disability. These patients tolerated clozapine treatment in the short term. Future studies are needed to thoroughly evaluate the long-term safety of clozapine treatment in this population.
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors.forename: Logan K
authors.initials: LK
authors.lastname: Wink
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors.forename: Ismail
authors.initials: I
authors.lastname: Badran
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors.forename: Ernest V
authors.initials: EV
authors.lastname: Pedapati
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors.forename: Rena
authors.initials: R
authors.lastname: Sorensen
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors.forename: Stacy C
authors.initials: SC
authors.lastname: Benton
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Johnson
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors.forename: Gregory
authors.initials: G
authors.lastname: Wissel
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, Ohio.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Erickson
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002658:Developmental Disabilities / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006760:Hospitalization; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D008297:Male; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: autism; autism spectrum disorder; clozapine; developmental delay; pharmacology