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Review
. 2025 Nov 9;14(22):7942.
doi: 10.3390/jcm14227942.

Metabolic and Endocrine ADRs of Atypical Antipsychotics (AAPs) in Paediatric Patients with Autism Spectrum Disorder (ASD): A Review of Prevalence, Risk Factors, and Implications for Clinical Monitoring

Mashal Aljead  1 , Aya Qashta  2 , Zahraa Jalal  1 , Alan M Jones  1
Affiliations
Review

Metabolic and Endocrine ADRs of Atypical Antipsychotics (AAPs) in Paediatric Patients with Autism Spectrum Disorder (ASD): A Review of Prevalence, Risk Factors, and Implications for Clinical Monitoring

Mashal Aljead et al. J Clin Med. .

Abstract

Atypical antipsychotics (AAPs) remain the most effective treatment to control irritability associated with autism spectrum disorder (ASD). Although there is no pharmaceutical treatment to target the core symptoms of ASD, AAPs reduce their severity. However, AAPs have been reported to be associated with severe adverse drug reactions (ADRs) that may lead to long-term conditions such as diabetes mellitus and heart disease. Their prevalence varies depending on the type of AAP prescribed, age, ethnicity, gender, healthcare systems, and the severity of the ASD. Current ADR monitoring guidelines exist, but they are broad in scope and do not fully account for these factors. Therefore, the need to develop ADR monitoring guidelines considering these factors has increased with the expanded use of AAPs in paediatrics with ASD. This gap in knowledge and clinical practice highlights the ongoing need for research to explore these factors and how they can inform the creation of tailored guidelines for monitoring ADRs in this population.

Keywords: adolescents; adverse drug reactions (ADRs); atypical antipsychotics (AAPs); autism spectrum disorder (ASD); children; endocrine side effects; metabolic side effects; monitoring guidelines; risk factors.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Mechanistic overview of atypical antipsychotics (AAPs)–induced metabolic dysregulation across multiple organ systems. Abbreviation: D2: Dopamine; 5-HT2A: 5-Hydroxytryptamine (Serotonin) 2A subtype; 5-HT2C: 5-Hydroxytryptamine (Serotonin) 2C subtype, H1: Histamine, α2: Alpha-2 adrenergic; M1: Muscarinic acetylcholine (M1 subtype); POMC: Pro-opiomelanocortin; α-MSH: Alpha-melanocyte-stimulating hormone; NPY: Neuropeptide Y; AgRP: Agouti-related peptide; AMPK: AMP-activated protein kinase; GLUT4: Glucose transporter 4, PI3K: Phosphoinositide 3-kinase; IRS: Insulin receptor substrate; ERK: Extracellular signal-regulated kinase; FFA: Free fatty acids; SLD: steatotic liver disease; GCGR: Glucagon receptor; PEPCK: Phosphoenolpyruvate carboxykinase; G6Pase: Glucose-6-phosphatase; SREBP1/2: Sterol regulatory element-binding protein ½; mTOR: Mammalian target of rapamycin; PPARγ: Peroxisome proliferator-activated receptor γ; IL-2: Interleukin-2; IL-6: Interleukin-6; TNF: Tumour necrosis factor; ↑: increase; ↓: decrease. Created in BioRender. Aljead, M. (2025) https://app.biorender.com/illustrations/6807a71b3c36b68f8a93e223.
Figure 2
Figure 2
Potential mechanism of AAPs inducing hyperprolactinaemia and their effects on sex organs and bone functions. Abbreviations: D2R: Dopamine D2 Receptor; AAPs: Atypical Antipsychotics; PRH: Prolactin-Releasing Hormone; GnRH: Gonadotropin-Releasing Hormone; FSH: Follicle-Stimulating Hormone; LH: Luteinizing Hormone; PRL: Prolactin; E2: Estradiol, T: Testosterone, BMD: Bone Mineral Density. ⊥: inhibition; ↶: stimulation; ↑↑: increase; ↓: decrease; Created in BioRender. Aljead, M. (2025) https://app.biorender.com/illustrations/6808f6c4346bb57af605562f.
Figure 3
Figure 3
Hypothesised mechanisms related to D2 and H1 Blockers, including thyroid dysfunction caused by Quetiapine. Abbreviation: QTP: Quetiapine, D2R: Dopamine D2 Receptor, H1R: Histamine H1 Receptor, TRH: Thyrotropin-Releasing Hormone, TSH: Thyroid-Stimulating Hormone, T3: Triiodothyronine, T4: Thyroxine; ⊥: inhibition; ↓↓: decrease Created in BioRender. Aljead, M. (2025) https://app.biorender.com/illustrations/680a5309a561a9a36a47aa85.
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References

    1. Hodges H., Fealko C., Soares N. Autism spectrum disorder: Definition, epidemiology, causes, and clinical evaluation. Transl. Pediatr. 2020;9((Suppl. 1)):S55. doi: 10.21037/tp.2019.09.09. - DOI - PMC - PubMed
    1. O’Nions E., Petersen I., Buckman J.E., Charlton R., Cooper C., Corbett A., Happé F., Manthorpe J., Richards M., Saunders R. Autism in England: Assessing underdiagnosis in a population-based cohort study of prospectively collected primary care data. Lancet Reg. Health Eur. 2023;29:100626. doi: 10.1016/j.lanepe.2023.100626. - DOI - PMC - PubMed
    1. AlBatti T.H., Alsaghan L.B., Alsharif M.F., Alharbi J.S., BinOmair A.I., Alghurair H.A., Aleissa G.A., Bashiri F.A. Prevalence of autism spectrum disorder among Saudi children between 2 and 4 years old in Riyadh. Asian J. Psychiatry. 2022;71:103054. doi: 10.1016/j.ajp.2022.103054. - DOI - PubMed
    1. Maenner M.J. Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and developmental disabilities monitoring network, 11 sites, United States, 2020. MMWR Surveill. Summ. 2023;72:1–14. doi: 10.15585/mmwr.ss7202a1. - DOI - PMC - PubMed
    1. Hassan A. Encyclopedia of Autism Spectrum Disorders. Springer; Berlin/Heidelberg, Germany: 2021. Arab views on autism; pp. 302–305.

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