Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2019 Oct 22;322(16):1561-1569.
doi: 10.1001/jama.2019.14685.

Effect of Fluoxetine on Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders: A Randomized Clinical Trial

Dinah S Reddihough  1   2   3 , Catherine Marraffa  1   2 , Anissa Mouti  4 , Molly O'Sullivan  2 , Katherine J Lee  2   3 , Francesca Orsini  2   3 , Philip Hazell  4 , Joanna Granich  5 , Andrew J O Whitehouse  5 , John Wray  6   7 , David Dossetor  4 , Paramala Santosh  8 , Natalie Silove  4 , Michael Kohn  4   9
Affiliations
Randomized Controlled Trial

Effect of Fluoxetine on Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders: A Randomized Clinical Trial

Dinah S Reddihough et al. JAMA. .

Abstract

Importance: Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain.

Objective: To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders.

Design, setting, and participants: Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017.

Interventions: Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks.

Main outcomes and measures: The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20; higher scores indicate higher levels of maladaptive behaviors; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables.

Results: Among the 146 participants who were randomized (85% males; mean age, 11.2 years), 109 completed the trial; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67; P = .21).

Conclusions and relevance: In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference.

Trial registration: anzctr.org.au Identifier: ACTRN12608000173392.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Drs Reddihough and Lee and Ms Orsini report receiving grants from NHMRC and the Royal Children's Hospital Foundation during the conduct of the study. Dr Hazell reports that his employer has received payment from Shire for speaker’s fees. Dr Whitehouse reports receiving grants from NHMRC during the conduct of the study. Dr Santosh reports that his employer has received payment from Medice for speaker’s fees, grants from Newron Pharma for conducting clinical trials, and he is a shareholder with Health Tracker Ltd, which has no relationship with the submitted work.. No other disclosures were reported.

Figures

Figure.
Figure.. Trial Profile, Including Assessment, Randomization, and Follow-up Through the Study of Fluoxetine for Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders
See this image and copyright information in PMC

Comment in

References

    1. Christensen DL, Braun KVN, Baio J, et al. . Prevalence and characteristics of autism spectrum disorder among children aged 8 years: Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2012. MMWR Surveill Summ. 2018;65(13):1-23. doi:10.15585/mmwr.ss6513a1 - DOI - PMC - PubMed
    1. Buescher AV, Cidav Z, Knapp M, Mandell DS. Costs of autism spectrum disorders in the United Kingdom and the United States. JAMA Pediatr. 2014;168(8):721-728. doi:10.1001/jamapediatrics.2014.210 - DOI - PubMed
    1. Soorya L, Kiarashi J, Hollander E. Psychopharmacologic interventions for repetitive behaviors in autism spectrum disorders. Child Adolesc Psychiatr Clin N Am. 2008;17(4):753-771, viii. doi:10.1016/j.chc.2008.06.003 - DOI - PubMed
    1. Aman MG, Lam KSL, Collier-Crespin A. Prevalence and patterns of use of psychoactive medicines among individuals with autism in the Autism Society of Ohio. J Autism Dev Disord. 2003;33(5):527-534. doi:10.1023/A:1025883612879 - DOI - PubMed
    1. Langworthy-Lam KS, Aman MG, Van Bourgondien ME. Prevalence and patterns of use of psychoactive medicines in individuals with autism in the Autism Society of North Carolina. J Child Adolesc Psychopharmacol. 2002;12(4):311-321. doi:10.1089/104454602762599853 - DOI - PubMed

Publication types

MeSH terms