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Cited by 415Autism Spectrum Disorder ResearchChild Nutrition and Feeding IssuesSchizophrenia research and treatment

Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)

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Williams, Katrina, Brignell, Amanda, Randall, Melinda, Silove, Natalie, Hazell, Philip·2013·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd004677.pub3PMC PMC11990048
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Abstract

BACKGROUND: Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of conditions often comorbid with ASD such as depression, anxiety and obsessive-compulsive behaviours. OBJECTIVES: To determine if treatment with an SSRI:1. improves the core features of autism (social interaction, communication and behavioural problems);2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;3. improves the quality of life of adults or children and their carers;4. has short- and long-term effects on outcome;5. causes harm. SEARCH METHODS: We searched the following databases up until March 2013: CENTRAL, Ovid MEDLINE, Embase, CINAHL, PsycINFO, ERIC and Sociological Abstracts. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). This was supplemented by searching reference lists and contacting known experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in people with ASD. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and appraised each study's risk of bias. MAIN RESULTS: Nine RCTs with a total of 320 participants were included. Four SSRIs were evaluated: fluoxetine (three studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (two studies). Five studies included only children and four studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence quotient of participants. Eighteen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis, except for one outcome (proportion improvement). One large, high-quality study in children showed no evidence of positive effect of citalopram. Three small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety. AUTHORS' CONCLUSIONS: There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.

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  • Many autistic individuals cannot tolerate or have limited effects from pharmacological treatments intended to impact psychiatric symptoms.

    “Many autistic individuals cannot tolerate or have limited effects from pharmacological treatments intended to impact psychiatric symptoms (LeClerc & Easley, 2015; Williams et al., 2013).”

    From Acceptance and commitment therapy for autistic adults: A randomized controlled pilot study in a psychiatric outpatient setting. (2023) · cites this paper as Williams et al., 2013

    The Background reports no evidence that SSRIs treat autism in children, limited evidence of effectiveness in adults, and possible side effects. The Discussion reports adverse events in some children but says the adult treatments were generally well tolerated. The review therefore supports limited effects and some tolerability concerns for SSRIs, not the broader claim that many autistic people cannot tolerate pharmacological treatments for psychiatric symptoms. (LLM, conf=0.84)

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  • Results of available clinical trials have been inconsistent in the benefits of SSRIs for improving aggression and the core symptoms of ASD.

    “However, results of available clinical trials have been inconsistent in the benefits of SSRI’s for improving aggression and the core symptoms of ASD [34].”

    From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [34]

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Research works printed but not linked: 4

  1. Gordon C, State R, Nelson J, Hamburger S, Rapoport J. A double‐blind comparison of clomipramine, desipramine, and of autistic disorder. Archives of General Psychiatry 1993;50(6):441‐7. [DOI] [PubMed] [Google Scholar]
  2. Bodfish JW, Symons FW, Lewis MH. The Repetitive Behavior Scale. Morganton, NC: Western Carolina Center Research Reports, 1999. [Google Scholar]
  3. Lefebvre C, Manheinmer E, Glanville J (editors). Chapter 6: Searching for Studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org. Chichester, UK: John Wiley & Sons.
  4. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.

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Authors
Williams, K., Brignell, A., Randall, M., Silove, N., & Hazell, P.
Affiliations
  • Royal Children's Hospital (AU)
  • Children's Hospital at Westmead (AU)
  • The University of Sydney (AU)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2013-08-20
Volume
2013
Issue
8
Pages
CD004677-CD004677
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd004677.pub3
PMC
PMC11990048
OpenAlex
W1906903025
Cited by
415
References
61
Citations by year
2026: 9 · 2025: 20 · 2024: 30 · 2023: 24 · 2022: 33 · 2021: 47 · 2020: 28 · 2019: 35 · 2018: 23 · 2017: 22 · 2016: 27 · 2015: 23 · 2014: 31 · 2013: 13 · 2012: 22
FWCI
2.66
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Bank (Australian Catholic University) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
autism spectrum disorder, selective serotonin reuptake inhibitors, fluoxetine, fluvoxamine, fenfluramine, citalopram, obsessive-compulsive behavior, self-harm, aggression, anxiety, social interaction, communication, quality of life, caregivers, adverse effects, children, adults, comorbid depression, anxiety comorbidity
MeSH terms
Adult, Age Factors, Autistic Disorder, Child, Child Development Disorders, Pervasive, Fenfluramine, Fluoxetine, Humans, Obsessive-Compulsive Disorder, Citalopram, Randomized Controlled Trials as Topic, Fluvoxamine, Selective Serotonin Reuptake Inhibitors

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