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Safety and Tolerability of Antipsychotic Medication in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

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Abstract

Background

Antipsychotic medication is a commonly prescribed drug class in individuals with autism spectrum disorder (ASD). However, the safety of these agents has not been fully assessed.

Objective

Our objective was to investigate the safety and tolerability profile of antipsychotics in individuals with ASD.

Methods

The Cochrane Library, MEDLINE, Embase and PsycINFO databases were searched up to January 2018. We included studies that reported adverse events (AEs) in participants with ASD taking first- or second-generation antipsychotic medication. The studies included in the analysis were randomized controlled trials (RCTs) and observational studies that were comparative or noncomparative and published as full text in the English language. The primary outcome of this review was AEs of any severity reported with antipsychotic use at any dose. Meta-analysis was performed on studies with child and adolescent participants to estimate the pooled prevalence of the overall AEs and the relative risk (RR) of AEs associated with antipsychotic use using a random-effects model. The Cochrane Collaboration tool and the modified Newcastle–Ottawa Scale (NOS) were used to assess the risk of bias of the included RCTs and observational studies, respectively.

Results

In total, 54 citations fulfilled the inclusion criteria, of which 40 were RCTs and 14 were observational studies; eight RCTs were included in the meta-analysis to estimate the RR of AEs associated with antipsychotic use and seven observational studies were included to estimate the pooled prevalence of AEs. The RR of AEs with antipsychotic treatment was 22% higher than with placebo (RR 1.22; 95% confidence interval [CI] 1.11–1.34; I2 = 30.6%; p = 0.184). The estimated pooled prevalence of AEs was 50.5% (95% CI 33–67). The most commonly reported AEs were increased appetite and weight gain, which were associated with discontinuation in many participants.

Conclusion

Antipsychotic-related AEs were common among patients with ASD. Further studies to investigate the implications of antipsychotic-related AEs on health and medication adherence are warranted. PROSPERO registration number: (CRD42018083632)

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Authors and Affiliations

  1. School of Pharmacy, University College London, London, UK

    Basmah H. Alfageh, Zixuan Wang, Pajaree Mongkhon, Frank M. C. Besag, Ruth Brauer & Ian C. K. Wong

  2. College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia

    Basmah H. Alfageh & Tariq M. Alhawassi

  3. School of Pharmaceutical Sciences, University of Phayao, Muang Phayao, Thailand

    Pajaree Mongkhon

  4. East London Foundation NHS Trust, Bedfordshire, UK

    Frank M. C. Besag

  5. Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Frank M. C. Besag

  6. Medication Safety Research Chair, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia

    Tariq M. Alhawassi

  7. Department of Pharmacology and Pharmacy, University of Hong Kong, Pokfulam, Hong Kong

    Ian C. K. Wong

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  1. Basmah H. Alfageh
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Corresponding author

Correspondence to Ian C. K. Wong.

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Conflict of interest

IW has received educational grants for projects unrelated to the current study from pharmaceutical companies that manufacture antipsychotic medicines and received research grants from the European Commission and Hong Kong Research Grant Council for the evaluation of antipsychotic drugs use in patients. BA, ZW, PM, FB, TA and RB have no conflicts of interest that are directly relevant to the content of this article.

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No sources of funding were used to conduct this study or prepare this manuscript.

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This article does not contain any studies with human participants or animals performed by any of the authors.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Alfageh, B.H., Wang, Z., Mongkhon, P. et al. Safety and Tolerability of Antipsychotic Medication in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Pediatr Drugs 21, 153–167 (2019). https://doi.org/10.1007/s40272-019-00333-x

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