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Cited by 482Autism Spectrum Disorder ResearchObsessive-Compulsive Spectrum DisordersChild Nutrition and Feeding Issues

Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior: Citalopram Ineffective in Children With Autism

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King, Bryan H., Hollander, Eric, Sikich, Linmarie, McCracken, James T., Scahill, Lawrence, Bregman, Joel D., Donnelly, Craig L., Anagnostou, Evdokia +5 more·2009·Archives of General Psychiatry
DOI 10.1001/archgenpsychiatry.2009.30PMC PMC4112556
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Abstract

CONTEXT: Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders. OBJECTIVES: To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders. DESIGN: National Institutes of Health-sponsored randomized controlled trial. SETTING: Six academic centers, including Mount Sinai School of Medicine, North Shore-Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School. PARTICIPANTS: One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. INTERVENTIONS: Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d). MAIN OUTCOME MEASURES: Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form. RESULTS: There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P > .99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], -2.0 [3.4] points for the citalopram-treated group and -1.9 [2.5] points for the placebo group; P = .81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus. CONCLUSION: Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645.

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Crossref · 10.1001/archgenpsychiatry.2009.30

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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 [100]

    The Results report that the 149-participant citalopram trial found no benefit over placebo and significantly more adverse events. But the Comment describes this as one large negative controlled study, not multiple large trials, and notes that a small fluoxetine trial found modest benefit and was well tolerated. The cited paper therefore does not support the claim as a general account of larger-scale SSRI trials in youth with ASD. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • King et al. 2009 completed a 12-week RCT of the SSRI citalopram in 149 youth with ASD (mean age = 9.4 years, range 5-17 years).

    “For example, King et al. 2009 completed a 12-week RCT of the SSRI citalopram in 149 youth with ASD (mean age = 9.4 years, range 5–17 years) [100].”

    From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [100]

  • Some studies have focused on the hypothesis that ASD may result from excessive excitation or insufficient inhibition at the level of neural circuits, with promising but inconclusive results for medicines targeting the GABAergic system.

    “A few studies have also focused on the hypothesis that, at the level of neural circuits, ASD may result from excessive excitation or insufficient inhibition 213 , with some promising but inconclusive results for medicines that target the GABAergic system 214 .”

    From Autism spectrum disorder (2020) · cites this paper as [214]

    The cited paper’s Comment section reports that citalopram, an SSRI, was not effective for repetitive behavior in children with ASD. Searches for GABAergic medicines and excitation–inhibition at the neural-circuit level found no passage addressing either point, so this paper cannot verify the claim attributed to it. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • The clinical scores most frequently used to measure treatment efficacy in clinical trials might be too focused on the core ASD symptoms and do not necessarily reflect improvements in quality of life.

    “Furthermore, the clinical scores most frequently used to measure treatment efficacy in clinical trials might be too focused on the core ASD symptoms and do not necessarily reflect improvements in quality of life 91 .”

    From Progress toward treatments for synaptic defects in autism (2013) · cites this paper as [91]

  • Standard treatments such as SSRIs or SNRIs, when effective in treating depression, likely ameliorate sociability deficits, but are commonly ineffective in treating large proportions of subjects with mood disorders.

    “It is likely that when effective in treating depression, standard treatments such as selective 5-HT reuptake inhibitors (SSRIs) or 5-HT and norepinephrine reuptake inhibitors (SNRIs) ameliorate sociability deficits but these are all too commonly ineffective in treating large proportions of subjects with mood disorders [3,170,171].”

    From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [170]

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Research works printed but not linked: 1

  1. [37]Jimmink A Caminada K Hunfeld NG Touw DJ Clinical toxicology of citalopram after acute intoxication with the sole drug or in combination with other drugs: overview of 26 cases Ther Drug Monit 2008 30 3 365 371 18520609

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Authors
King, B. H., Hollander, E., Sikich, L., McCracken, J. T., Scahill, L., Bregman, J. D., Donnelly, C. L., Anagnostou, E., Dukes, K., Sullivan, L., Hirtz, D., Wagner, A., & Ritz, L.
Affiliations
  • Seattle Children's Hospital (US)
  • University of North Carolina at Chapel Hill (US)
  • Dartmouth College (US)
  • Boston University (US)
ORCID
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
2009-06-01
Volume
66
Issue
6
Pages
583
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archgenpsychiatry.2009.30
PMC
PMC4112556
OpenAlex
W2116795013
Cited by
482
References
42
Citations by year
2026: 11 · 2025: 16 · 2024: 26 · 2023: 17 · 2022: 19 · 2021: 32 · 2020: 31 · 2019: 22 · 2018: 23 · 2017: 21 · 2016: 21 · 2015: 29 · 2014: 32 · 2013: 39 · 2012: 51
FWCI
23.31
Type
journal article
Language
en
Open access
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5u54mh066418-05)
  • National Institute of Mental Health (U54MH066494, U54-MH066418, U54MH066673, U54MH066398, U54MH068172)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01HD045023)
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
autism spectrum disorder, repetitive behavior, obsessive-compulsive symptoms, selective serotonin reuptake inhibitors, children, Asperger syndrome, pervasive developmental disorders, treatment efficacy, adverse events, clinical global impression, Children's Yale-Brown Obsessive Compulsive Scale, drug safety in children
MeSH terms
Adolescent, Attention, Autistic Disorder, Child, Child Development Disorders, Pervasive, Child, Preschool, Diarrhea, Dose-Response Relationship, Drug, Female, Humans, Impulsive Behavior, Sleep Initiation and Maintenance Disorders, Male, Motor Activity, Stereotyped Behavior, Citalopram, Treatment Failure, Selective Serotonin Reuptake Inhibitors, Asperger Syndrome

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