A Retrospective Naturalistic Study of Ziprasidone for Irritability in Youth with Autism Spectrum Disorder.

Objective: The purpose of this study was to assess the impact of ziprasidone monoantipsychotic treatment targeting irritability in a naturalistic outpatient autism spectrum disorder (ASD) clinical setting.

Methods: We examined the use of ziprasidone, predominantly in combination with other psychotropic agents, targeting irritability in 42 youth with ASD in a large ASD-specific treatment database. Mean age at start of treatment, treatment duration, final dose, body mass index (BMI), BMI Z score, and Clinical Global Impressions-Improvement Scale (CGI-I) score at final visit were determined, and changes with treatment were analyzed using paired t tests. Cardiac corrected QT (QTc) interval data were extracted from electrocardiograms when available.

Results: Mean age at start of treatment was 11.8 years. And final mean dose of ziprasidone was 98.7 mg/day or 1.7 mg/kg/day. Seventeen (40%) participants were considered treatment responders based on the CGI-I. No changes in QTc (although only examined in nine participants), weight, BMI, or other vital signs were noted, with ziprasidone use. The rate of treatment response was less than what has been reported for the two atypical antipsychotics, risperidone and aripiprazole, approved by the Food and Drug Administration (FDA) for the treatment of irritability in autistic disorder. The response rate with ziprasidone may be more consistent with response rates for other atypical antipsychotics, although none of these agents has been studied in larger-scale double-blind, placebo-controlled trials. The lower rate of response to ziprasidone in this open-label trial is likely influenced by the treatment-refractory nature of the population studied.

Conclusions: The weight neutrality of ziprasidone appears favorable compared with other second generation antipsychotics in this population. The response rate to ziprasidone targeting irritability may be lower than response rates associated with FDA-approved agents for this indication. Overall, ziprasidone use appeared well tolerated in youth with ASD.

Competing Interests: Dr. Erickson holds equity in Confluence Pharmaceuticals, and has served as a consultant to Confluence Pharmaceuticals, Alcobra Pharmaceuticals, and the Roche Group. Dr. Wink has served as a consultant to Otsuka Pharmaceuticals. Drs. McDougle and Dominick have no potential conflicts of interest to disclose.