Sedation and its Potential Risks in Children with Autism Spectrum Due to Drug Overlaps: A Critical Review


  • Herculano Ramirez Floro Alonso
  • Mônica Vilela Heimer
  • Rafael Vrijdags Calado
  • João Victor Farias da Silva
  • Renata Matos Lamenha Lins
  • Dayse Andrade Romão
  • Daniela Maria Carvalho Pugliesi
  • Valdeci Elias dos Santos Junior


Mental Health, Autistic Disorder, Child Development, Pharmacology


Objective: To analyse pharmacological overlap in patients with autism spectrum disorder (ASD) under conscious sedation in a dental office environment, identifying any potential risks and complications. Material and Methods: A critical review was conducted by selecting articles from online databases (Pubmed and Lilacs), using a search algorithm and eligibility criteria. The Medscape® platform was used to verify interactions between drugs commonly used by patients with ASD and medications used for sedation in paediatric dentistry. Results: Due to their polydrug use, children with ASD are at risk of complications, namely Serotonin Syndrome (SS), Neuroleptic Malignant Syndrome (NMS), increase or decrease of the QT interval (QTi) and Torsade de Pointes (TdP), due to pre-existence of metabolic syndrome, deepening the sedation level or even leading to a decrease in the sedative capacity of the drugs used. Conclusion: It is essential to assess better drug interaction in ASD patients submitted to sedation. The severity of the disorder and the need for sedation for dental treatment are directly proportional. However, increases in sedative doses tend to increase risks and complications in children with ASD.


Hyman SL, Levy SE, Myers SM; Council on Children with Disabilities, Section on Developmental and Behavioral Pediatrics. Identification, evaluation, and management of children with autism spectrum disorder. Pediatrics 2020; 145(1):e20193447.

Autism spectrum disorder in under 19s: recognition, referral and diagnosis. London: National Institute for Health and Care Excellence (NICE); 2017. 45 p. Available from: [Accessed on June 30, 2021].

Howes OD, Rogdaki M, Findon JL, Wichers RH, Charman T, King BH, et al. Autism spectrum disorder: Consensus guidelines on assessment, treatment and research from the British Association for Psychopharmacology. J Psychopharmacol 2018; 32(1):3-29.

Lamy M, Erickson CA. Pharmacological management of behavioral disturbances in children and adolescents with autism spectrum disorders. Curr Probl Pediatr Adolesc Health Care 2018; 48(10):250-264.

Coté CJ, Wilson S; American Academy of Pediatrics; American Academy of Pediatric Dentistry. Guidelines for monitoring and management of pediatric patients before, during, and after sedation for diagnostic and therapeutic procedures. Pediatrics 2019; 143(6):e20191000.

Miyake RS, Reis AG, Grisi S. Sedação e analgesia em crianças. Rev Assoc Med Bras 1998; 44(1):56-64. [In Portuguese].

Aishworiya R, Valica T, Hagerman R, Restrepo B. An update on psychopharmacological treatment of autism spectrum disorder. Neurotherapeutics 2022; 19(1):248-262.

Eissa N, Al-Houqani M, Sadeq A, Ojha SK, Sasse A, Sadek B. Current enlightenment about etiology and pharmacological treatment of autism spectrum disorder. Front Neurosci 2018; 12:304.

Persico AM, Ricciardello A, Lamberti M, Turriziani L, Cucinotta F, Brogna C, et al. The pediatric psychopharmacology of autism spectrum disorder: A systematic review - Part I: The past and the present. Prog Neuropsychopharmacol Biol Psychiatry 2021; 110:110326.

Malamed SF. Sedação Oral. Sedação na Odontologia. 5th ed. Rio de Janeiro: Elsevier; 2012. p. 95-118. [In Portuguese].

Dock M. Abordagem Farmacológica do Comportamento do Paciente. In: Dean JA, Avery DR, McDonald RE, editors. McDonald e Avery Odontopediatria para Crianças e Adolescentes. 9th ed. Rio de Janeiro: Elsevier; 2011. p. 249-72. [In Portuguese].

Drug Interaction Checker. New York: Medscape Reference; 1995. Available from: [Accessed on September 24, 2022].

Taniguchi C, Guengerich FP. Metabolismo dos fármacos. In: Golan DE, Tashjian Junior AH, Armstrong EJ, Armstrong AW, editors. Princípios de Farmacologia: A Base Fisiopatológica da Farmacoterapia. 2nd ed. Rio de Janeiro: Guanabara-Koogan; 2009. p. 46–57. [In Portuguese].

Taniguchi CM, Armstrong SR, Green LC, Golan DE, Tashjian Jr. AH. Toxicidade dos fármacos. In: Golan DE, Tashjian Junior AHAEJ, Armstrong AW, editors. Princípios de farmacologia: A base fisiopatológica da farmacoterapia. 2nd ed. Rio de Janeiro: Guanabara Koogan; 2009. p. 58-68. [In Portuguese].

Chieh AY, Bryant BM, Kim JW, Li L. Systematic review investigating the relationship between autism spectrum disorder and metabolic dysfunction. Res Autism Spectr Disord 2021; 86:101821.

Midazolam [package insert]. Sabará, MG: Hipolabor Farmacêutica Ltda.; 2022. [In Portuguese].

Asahi Y, Kubota K, Omichi S. Dose requirements for propofol anaesthesia for dental treatment for autistic patients compared with intellectually impaired patients. Anaesth Intensive Care 2009; 37(1):70-73.

Seo KH, Jung HS, Kang EG, Kim CJ, Rhee HY, Jeon YS. Sedation using 5% lidocaine patches, Midazolam and propofol in a combative, obese adolescent with severe autistic disorder undergoing brain magnetic resonance imaging: a case report. Korean J Anesthesiol 2014; 67(6):421-424.

Berkenbosch JW, Nguyen T-Q, Emmanouil D, Hardan AY. Special considerations during sedation of the child with autism spectrum disorder. In: Mason KP, editor. Pediatric Sedation Outside of the Operating Room. 3rd ed. Cham: Springer; 2021. p. 545-560.

Ashley P, Anand P, Andersson K. Best clinical practice guidance for conscious sedation of children undergoing dental treatment: an EAPD policy document. Eur Arch Paediatr Dent 2021; 22(6):989-1002.

Malamed SF. Condutas emergenciais. Sedação na Odontologia. 5th. ed. Rio de Janeiro: Elsevier; 2012. p. 446-481. [In Portuguese].

Posey DJ, McDougle CJ. Guanfacine and guanfacine extended release: treatment for ADHD and related disorders. CNS Drug Rev 2007; 13(4):465-474.

Cintra P, Ramos A. Síndrome serotoninérgico: Manifestações clínicas, diagnóstico e terapêutica. Psilogos 2008; 5(1-2):88-96. [In Portuguese].

Relia S, Ekambaram V. Pharmacological approach to sleep disturbances in autism spectrum disorders with psychiatric comorbidities: A literature review. Med Sci 2018; 6(4):95.

Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: A brief review. CMAJ 2003; 168(11):1439-1442. Available from: [Accessed on September 24, 2022].

Khan S, Saud S, Khan I, Asif M, Ismail O, Salam A, et al. Serotonin syndrome presenting with concomitant tramadol and diphenhydramine use: A case report of an unlikely side-effect. Cureus 2018; 10(4):e2421.

Racz R, Soldatos TG, Jackson D, Burkhart K. Association between serotonin syndrome and second-generation antipsychotics via pharmacological target-adverse event analysis. Clin Transl Sci 2018; 11(3):322-329.

Direk MÇ, Yıldırım V, Güneş S, Bozlu G, Okuyaz Ç. Serotonin syndrome after clomipramine overdose in a child. Clin Psychopharmacol Neurosci 2016; 14(4):388-390.

American Psychiatric Association (APA). DSM-5: Manual Diagnóstico e Estatístico de Transtornos Mentais. 5th. ed. Porto Alegre: Artmed; 2014. p. 709-711. [In Portuguese].

Souza RAP, Silva MAF, Coelho DM, Galvão MLS, Souza NAC, Picão AP. Síndrome neuroléptica maligna. Rev Bras Clin Med 2012; 10(5):440-445. [In Portuguese].

Berloffa S, Dosi C, Tascini B, Fossati B, Lupetti I, Masi G. Neuroleptic malignant syndrome in children with Autism Spectrum Disorder (ASD): A case report and brief review of recent literature. Children 2021; 8(12):1201.

Pytliak M, Vargová V, Mechírová V, Felšöci M. Serotonin receptors - From molecular biology to clinical applications. Physiol Res 2011; 60(1):15-25.

Richelson E. Pharmacology of antidepressants. Mayo Clin Proc 2001; 76(5):511-527.

Standaert DG, Galanter JM. Farmacologia da Neurotransmissão Dopaminérgica. In: Golan DE, Tashjian Junior AH, Armstrong EJ, Armstrong AW, editors. Princípios de Farmacologia: a Base Fisiopatológica da Farmacoterapia. 2nd ed. Rio de Janeiro: Guanabara Koogan; 2009. p. 166-185. [In Portuguese].

Criado PR, Criado RF, Maruta CW, Machado Filho Cd. Histamina, receptores de histamina e anti-histamínicos: Novos conceitos. An Bras Dermatol 2010; 85(2):195-210. [In Portuguese].

Griffin Jr. EA, Lowenstein DH. Farmacologia da neurotransmissão elétrica anormal no sistema nervoso central. In: Golan DE, Tashjian Junior AH, Armstrong EJ, Armstrong AW, editors. Princípios de Farmacologia: A Base Fisiopatológica da Farmacoterapia. 2nd ed. Rio de Janeiro: Guanabara Koogan; 2009. p. 203-216. [In Portuguese].

Borroto-Escuela DO, Ambrogini P, Narvaez M, Di Liberto V, Beggiato S, Ferraro L, et al. Serotonin heteroreceptor complexes and their integration of signals in neurons and astroglia-relevance for mental diseases. Cells 2021; 10(8):1902.

Ishii T, Kimura Y, Ichise M, Takahata K, Kitamura S, Moriguchi S, et al. Anatomical relationships between serotonin 5-HT2A and dopamine D2 receptors in living human brain [published correction appears in PLoS One 2018; 13(5):e0197201]. PLoS One 2017; 12(12):e0189318.

Vo LC, Snyder C, McCracken C, McDougle CJ, McCracken JT, Aman MG, et al. No apparent cardiac conduction effects of acute treatment with risperidone in children with autism spectrum disorder. J Child Adolesc Psychopharmacol 2016; 26(10):900-908.

Shah RR. Drug-induced QT interval shortening: Potential harbinger of proarrhythmia and regulatory perspectives. Br J Pharmacol 2010; 159(1):58-69.

Ribeiro S. Síndrome de QT Longo. Rev Cardiopulmonar 2006; 17(1):43-49. [In Portuguese].

Martins JM, Figueiredo TP, Costa SC, Reis AMM. Medicamentos que podem induzir prolongamento do intervalo QT utilizados por idosos em domicílio. Rev Ciênc Farm Básica Apl 2015; 36(2):297-305. [In Portuguese].

Endres D, Decher N, Röhr I, Vowinkel K, Domschke K, Komlosi K, et al. New Cav1.2 channelopathy with high-functioning autism, affective disorder, severe dental enamel defects, a short QT Interval, and a novel CACNA1C loss-of-function mutation. Int J Mol Sci 2020; 21(22):8611.

Timothy Syndrome. Danbury (CT): National Organization for Rare Disorders (NORD); c2005-2020 [updated 2020]. Available from: [Accessed on May 16, 2022].

Husain Z, Hussain K, Nair R, Steinman R. Diphenhydramine induced QT prolongation and torsade de pointes: An uncommon effect of a common drug. Cardiol J 2010; 17(5):509-511.

Timour Q, Frassati D, Descotes J, Chevalier P, Christé G, Chahine M. Sudden death of cardiac origin and psychotropic drugs. Front Pharmacol 2012; 3:76.

Staikou C, Stamelos M, Stavroulakis E. Impact of anaesthetic drugs and adjuvants on ECG markers of torsadogenicity. Br J Anaesth 2014; 112(2):217-230.

Höcht C, Opezzo JAW, Taira CA. Intervalo QT prolongado inducido por fármacos desde el punto de vista de un farmacólogo. Rev Argent Cardiol 2004; 72(6):474-480. [In Spanish].

Zeltser D, Justo D, Halkin A, Prokhorov V, Heller K, Viskin S. Torsade de pointes due to noncardiac drugs: Most patients have easily identifiable risk factors. Medicine 2003; 82(4):282-290.

Carvalho MVH, Carvalho VN, Falani FS. Alterações eletrocardiográficas em crianças e jovens assistidos pela Associação dos Pais e Amigos dos Excepcionais (APAE). Rev Med UFPR 2017; 4(1):11-16. [In Portuguese].

Hidroxizina [package insert]. Juiz de Fora, MG: Nativita Indústria e Comércio Ltda.; 2022. [In Portuguese].




How to Cite

Alonso, H. R. F., Heimer, M. V., Calado, R. V., da Silva, J. V. F., Lins, R. M. L., Romão, D. A., Pugliesi, D. M. C., & dos Santos Junior, V. E. (2024). Sedation and its Potential Risks in Children with Autism Spectrum Due to Drug Overlaps: A Critical Review. Pesquisa Brasileira Em Odontopediatria E Clínica Integrada, 24, e220170. Retrieved from



Critical Review / Scope Review