The SOFIA Study: Negative Multi-center Study of Low Dose Fluoxetine on Repetitive Behaviors in Children and Adolescents with Autistic Disorder
Abstract
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that reduces obsessive-compulsive symptoms. There is limited evidence supporting its efficacy for repetitive behaviors (RRBs) in autistic spectrum disorder (ASD). We conducted a randomized controlled trial (RCT) of fluoxetine in 158 individuals with ASD (5-17 years). Following 14 treatment weeks (mean dose 11.8 mg/day), no significant differences were noted on the Children's Yale-Brown Obsessive Compulsive Scale; the proportion of responders was similar (fluoxetine: 36%; placebo: 41%). There were similar rates of AEs (e.g., insomnia, diarrhea, vomiting); high rates of activation were reported in both groups (fluoxetine: 42%; placebo: 45%). Overly cautious dosing/duration may have prevented attainment of a therapeutic level. Results are consistent with other SSRI RCTs treating RRBs in ASD.Trial Registration: clinicaltrials.gov Identifier: NCT00515320.
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Larger-scale, double-blind, placebo-controlled trials of SSRIs for youth with ASD have not found the drug to be better than placebo, and significant adverse effects are common.
“However, larger-scale, double-blind, placebo-controlled trials of SSRIs for youth with ASD have not found the drug to be better than placebo, and significant adverse effects are common.”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [101]
The Study of Fluoxetine in Autism (SOFIA) was a 14-week RCT of the SSRI fluoxetine (2-18 mg/day) in 158 youth with ASD, ages 5-17 years.
“The Study of Fluoxetine in Autism (SOFIA) was a 14-week RCT of the SSRI fluoxetine (2–18 mg/day) in 158 youth with ASD, ages 5–17 years [101].”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [101]
The results showed that fluoxetine was no more efficacious than placebo for repetitive behavior.
“The results showed that fluoxetine was no more efficacious than placebo for repetitive behavior.”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [101]
High rates of behavioral activation were reported in both groups.
“High rates of behavioral activation were reported in both groups [101].”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [101]
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Solmi, M., Fornaro, M., Ostinelli, E. G., Zangani, C., Croatto, G., Monaco, F., Krinitski, D., Fusar‐Poli, P., & Correll, C. U. (2020) · World Psychiatry · doi:10.1002/wps.20765 · Cited by 324 · see citing works
Bennett (2023) · doi:10.1097/yco.0000000000000775 · Cited by 51 · see citing works
Manter, M. A., Birtwell, K. B., Bath, J., Friedman, N. D. B., Keary, C. J., Neumeyer, A. M., Palumbo, M. L., Thom, R. P., Stonestreet, E., Brooks, H., et al. (2025) · BMC Medicine · doi:10.1186/s12916-024-03814-0 · Cited by 51 · see citing works
“High rates of behavioral activation were reported in both groups [101].”
McDougle, C. J., Thom, R. P., Ravichandran, C. T., Palumbo, M. L., Politte, L. C., Mullett, J. E., Keary, C. J., Erickson, C. A., Stigler, K. A., Mathieu-Frasier, L., et al. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01295-4 · Cited by 31 · see citing works
- Authors
- Herscu, P., Handen, B. L., Arnold, L. E., Snape, M. F., Bregman, J. D., Ginsberg, L., Hendren, R., Kolevzon, A., Melmed, R., Mintz, M., Minshew, N., Sikich, L., Attalla, A., King, B., Owley, T., Childress, A., Chugani, H., Frazier, J., Cartwright, C., Murphy, T., & the Autism Speaks Autism Clinical Trials Network
- Affiliations
- University of Pittsburgh (US)
- The Ohio State University (US)
- AMO Pharma (United Kingdom) (GB)
- Northwell Health (US)
- University of California, San Francisco (US)
- Icahn School of Medicine at Mount Sinai (US)
- Southwest Autism Research & Resource Center (US)
- University of North Carolina at Chapel Hill (US)
- Institute for Behavioral Medicine (US)
- University of Illinois Chicago (US)
- Center for Psychiatry and Behavioral Medicine (US)
- NYU Langone Health (US)
- Cambridge Health Alliance (US)
- Spectrum Health (US)
- University of Florida (US)
- Corresponding author
- Handen, Benjamin L.
- ORCID
- Venue
- Journal of Autism and Developmental Disorders
- Published
- 2019-07-02
- Volume
- 50
- Issue
- 9
- Pages
- 3233-3244
- ISSN
- 0162-3257 (ISSN-L)
- 1573-3432
- OpenAlex
- W2953462834
- Cited by
- 62
- References
- 7
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 14 · 2023: 8 · 2022: 11 · 2021: 11 · 2020: 7
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Autism and Developmental Disorders (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- Neuropharm PLC
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- fluoxetine, repetitive behavior, autism spectrum disorder, obsessive-compulsive symptoms, selective serotonin reuptake inhibitors, children and adolescents, treatment response, adverse events
- MeSH terms
- Adolescent, Autistic Disorder, Child, Child, Preschool, Dose-Response Relationship, Drug, Double-Blind Method, Female, Fluoxetine, Humans, Male, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Stereotypic Movement Disorder
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