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Paliperidone for irritability in adolescents and young adults with autistic disorder

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Abstract

Rationale

Individuals with autistic disorder (autism) frequently exhibit significant irritability marked by severe tantrums, aggression, and self-injury. Despite advances in the treatment of this symptom domain in autism, there remains an ongoing need for more effective and better tolerated pharmacotherapies.

Objectives

The aim of this study is to determine the effectiveness and tolerability of paliperidone for irritability in autism.

Methods

This is a prospective, 8-week open-label study of paliperidone in 25 adolescents and young adults with autism. Primary outcome measures included the Clinical Global Impressions-Improvement (CGI-I) Scale and the Irritability subscale of the Aberrant Behavior Checklist (ABC-I). Concomitant medications (except antipsychotics) were permitted if dosages were stable for ≥2 months.

Results

Twenty-one (84 %) of 25 subjects ages 12–21 years (mean 15.3 years) responded to paliperidone, based on a CGI-I Scale score of 1 or 2 (very much or much improved) and ≥25 % improvement on the ABC-I. The mean final dosage of paliperidone was 7.1 mg/day (range 3–12 mg/day). Two subjects discontinued paliperidone prior to study completion (moderate sedation, n = 1; nonresponse, n = 1). Mild-to-moderate extrapyramidal symptoms were recorded in four subjects. A mean weight gain of 2.2 ± 2.6 kg (range −3.6 to +7.9 kg) was recorded. Mean age- and sex-normed body mass index increased from 23.6 to 24.2 (p ≤ 0.001). Mean serum prolactin increased from 5.3 to 41.4 ng/mL (p ≤ 0.0001).

Conclusions

Paliperidone treatment was associated with significant improvement in irritability and was generally well tolerated. Larger scale, placebo-controlled studies are needed to elucidate the efficacy and tolerability of paliperidone in this population.

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Acknowledgments

This study was supported, in part, by a Daniel X. and Mary Freedman Fellowship in Academic Psychiatry (Dr. Stigler), an investigator-initiated research grant from Janssen Scientific Affairs, L.L.C. (Dr. Stigler), a Career Development Award (K23 MH082119) from the National Institute of Mental Health (NIMH) (Dr. Stigler), the Indiana Division of Developmental Disability and Rehabilitative Services (Drs. McDougle and Erickson), and a research grant (R01 MH072964) from the NIMH (Dr. McDougle).

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Authors and Affiliations

  1. Section of Child and Adolescent Psychiatry, Department of Psychiatry, Indiana University School of Medicine, Christian Sarkine Autism Treatment Center, James Whitcomb Riley Hospital for Children, 705 Riley Hospital Drive, Indianapolis, IN, 46202-5200, USA

    Kimberly A. Stigler, Jennifer E. Mullett, Craig A. Erickson, David J. Posey & Christopher J. McDougle

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  1. Kimberly A. Stigler
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  2. Jennifer E. Mullett
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  3. Craig A. Erickson
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  4. David J. Posey
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  5. Christopher J. McDougle
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Correspondence to Kimberly A. Stigler.

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Stigler, K.A., Mullett, J.E., Erickson, C.A. et al. Paliperidone for irritability in adolescents and young adults with autistic disorder. Psychopharmacology 223, 237–245 (2012). https://doi.org/10.1007/s00213-012-2711-3

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  • DOI: https://doi.org/10.1007/s00213-012-2711-3

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