Background: Risperidone is a common psychopharmacological treatment for irritability in autism spectrum disorder (ASD). It is not well-established how effective risperidone is across the initial symptom severity range. This study aims to examine the influence of baseline severity on the efficacy of risperidone in the treatment of ASD. Methods: Participants were from the NIMH funded RUPP multisite, randomized, double-blind trial that compared risperidone to placebo to treat autistic disorder with severe tantrums, aggression, or self-injury. Participants were aged 5 to 17, and randomly assigned to risperidone (n = 49) or placebo (n = 52). Baseline and change scores were computed with the Aberrant Behavior Checklist (ABC) parent assessed scales with irritability as the primary outcome, as well as the clinician assessed ABC Irritability subscale, and Clinical Global Impression Scale. Results: The relationship between baseline severity and change scores for the risperdone and placebo groups was examined with eight competing three-level mixed-effects models for repeated measure models. Significant (P < 0.01) interactions between treatment and baseline severity were observed for parent ABC ratings of irritability and lethargy only. Greater magnitudes of the differences between risperidone and placebo were observed from moderate to very severe baseline severity on irritability and lethargy. Initial severity values over approximately 30 had a strong effect on symptom change [irritability: effect size (ES) = 1.9, number needed to treat (NNT) = 2, lethargy ES = 0.9, NNT = 5]. Conclusions: Parents may expect benefits of risperidone on irritability and lethargy with moderate to severe symptoms of ASD. Trial registration: Registry name: ClinicalTrials.gov, trial identifier: NCT00005014, URL: http://www.clinicaltrials.gov/ct2/show/NCT00005014?term=NCT00005014&rank=1, registered on March 31, 2000.
Bibliographical noteFunding Information:
Data used in the preparation of this article were obtained from the limited access datasets distributed from the NIH-supported Research Units on Pediatric Psychopharmacology's “Placebo-Controlled Study of Risperidone for the Treatment of Children and Adolescents With Autism and Negative Behavioral Symptoms” (RUPP Autism). This is a multisite, placebo-controlled, double-blind clinical trial designed to determine the safety and efficacy of risperidone in children and adolescents with Autistic Disorder. The study was supported by NIMH Contract #s N01MH70001, N01MH70009, N01MH80011, N01MH70010, and N01MH70001. The ClinicalTrials.gov identifier: NCT00005014 . This manuscript reflects the views of the authors and may or may not reflect the opinions or views of the RUPP Autism Study Investigators or the NIMH. Role of funding source : none.
This study received no external funding. In unrelated work, Dr Levine has received honoraria and/or research support, and/or consultancy fees and/or travel support from Shire, F. Hoffmann-La Roche and Eli Lilly. Dr Furukawa has received lecture fees from Eli Lilly, Meiji, Mochida, MSD, Pfizer and Tanabe-Mitsubishi, and consultancy fees from Sekisui and Takeda Science Foundation. He is diplomate of the Academy of Cognitive Therapy. He has received royalties from Igaku-Shoin, Seiwa-Shoten and Nihon Bunka Kagaku-sha. The Japanese Ministry of Education, Science, and Technology, the Japanese Ministry of Health, Labor and Welfare, and the Japan Foundation for Neuroscience and Mental Health have funded his research projects. Dr Leucht has received honoraria for consultation or for participation in advisory boards from Alkermes, Bristol-Myers Squibb, Eli Lilly, Janssen, Johnson & Johnson, Lundbeck, MedAvante, and Roche; and lecture honoraria from Abbvie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, EssexPharma, Janssen, Johnson & Johnson, Lundbeck, Pfizer, and Sanofi-Aventis. Eli Lilly has also provided drugs for a trial for which Dr Leucht is the primary investigator. Dr Arad Kodesh is an employee of HaMeuchedet Healthcare Services. Dr. Kolevzon receives research support from Neuren Pharmaceuticals and Hoffmann-La Roche. Drs Reichenberg and Goldberg report no commercial conflict of interest.
© 2015 Elsevier Masson SAS.
- Baseline severity
- Clinical trial
ASJC Scopus subject areas
- Psychiatry and Mental health