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Cited by 37Autism Spectrum Disorder ResearchBehavioral and Psychological StudiesChild Nutrition and Feeding Issues

Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment

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Choi, Hangnyoung, Kim, Jae Han, Yang, Hee Sang, Kim, Jong Yeob, Cortese, Samuele, Smith, Lee, Koyanagi, Ai, Dragioti, Elena +5 more·2024·Molecular Autism
DOI 10.1186/s13229-024-00585-6PMC PMC10807060
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Abstract

Background: Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. Methods: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges’ g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. Results: Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges’ g − 0.857, 95% CI − 1.263 to − 0.451, certainty of evidence: high) and aripiprazole (Hedges’ g − 0.559, 95% CI − 0.767 to − 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges’ g − 0.893, 95% CI − 1.184 to − 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. Limitations: First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. Conclusions: Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.

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Authors
Choi, H., Kim, J. H., Yang, H. S., Kim, J. Y., Cortese, S., Smith, L., Koyanagi, A., Dragioti, E., Radua, J., Fusar-Poli, P., Shin, J. I., Cheon, K.-A., & Solmi, M.
Affiliations
  • Yonsei University (KR)
  • Solent NHS Trust (GB)
  • Anglia Ruskin University (GB)
  • Parc Sanitari Sant Joan de Déu (ES)
  • Linköping University (SE)
  • University of Ottawa (CA)
Corresponding author
  • Shin, Jae Il
  • Cheon, Keun-Ah
ORCID
Venue
Molecular Autism
Publisher
Springer Science and Business Media LLC
Published
2024-01-23
Volume
15
Issue
1
Pages
7-7
ISSN
2040-2392 (ISSN-L)
DOI
10.1186/s13229-024-00585-6
PMC
PMC10807060
OpenAlex
W4391124873
Cited by
37
References
9
Citations by year
2026: 12 · 2025: 17 · 2024: 8
FWCI
2.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Autism (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • DiVA (Linkoping University) (submittedVersion, other-oa)
  • Research Portal (King's College London) (submittedVersion, cc-by)
  • PUBLISSO (German National Library of Medicine) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by-nc-nd)
  • uO Research (University of Ottawa) (submittedVersion, public-domain)
Funders
National Center for Mental Health (MHER22A01)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
Keywords
autism spectrum disorder, irritability, pharmacological interventions, non-pharmacological treatment, risperidone, aripiprazole, parent training, dietary supplementation, adjuvant therapy, antipsychotic augmentation, treatment efficacy, quality of evidence, risk of bias assessment, GRADE assessment, outcome heterogeneity, children and adolescents
MeSH terms
Autism Spectrum Disorder, Aripiprazole, GRADE Approach, Female, Humans, Male, Risperidone

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