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Antipsychotic long-term treatment in children and young people: a systematic review and meta-analysis of efficacy and tolerability across mental health and neurodevelopmental conditions

Published online by Cambridge University Press:  24 May 2021

Pushpika Singappuli Open the ORCID record for Pushpika Singappuli [Opens in a new window] ,
Edmund Sonuga-Barke  and
Marinos Kyriakopoulos Open the ORCID record for Marinos Kyriakopoulos [Opens in a new window]
Pushpika Singappuli*
Affiliation:
Child and Adolescent Mental Health Services Clinical Academic Group, South London and Maudsley NHS Foundation Trust, London, United Kingdom
Edmund Sonuga-Barke
Affiliation:
Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
Marinos Kyriakopoulos
Affiliation:
Child and Adolescent Mental Health Services Clinical Academic Group, South London and Maudsley NHS Foundation Trust, London, United Kingdom Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
*
*Author for correspondence: Pushpika Singappuli Email: [email protected]
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Abstract

Antipsychotic medications are used in a wide range of mental health and neurodevelopmental conditions in children and adolescents. Their efficacy and tolerability with long-term use have not been clearly established. We aimed to conduct a systematic review and meta-analysis to evaluate the long-term use of antipsychotics in children and adolescents. All relevant double-blind randomized control trials (RCTs), on any antipsychotic used for 12 weeks or longer in any mental health/neurodevelopmental condition in this age group, were included. We evaluated several efficacy and tolerability measures. Meta-analysis was performed for adverse events. Seven RCTs were identified (n = 939, age = 5-17 years), four on aripiprazole and three on risperidone. All studies reported symptomatic/functional improvements or more time before discontinuation with antipsychotics compared to placebo. Weight gain was identified as a significant side effect with antipsychotics. Serum prolactin was reduced with aripiprazole and increased with risperidone, and abdominal pain/discomfort, respiratory tract infections, were more common with Aripiprazole compared to placebo. Musculoskeletal pain may be more common with aripiprazole compared to placebo. Use of antipsychotics for 12 weeks or longer may be associated with symptomatic/functional improvements, but may be associated with additional side effects compared to short-term treatment. Further research in this population is needed.

Keywords

Antipsychoticslong-termchildrenadolescentsefficacytolerability
Type
Review
Information
CNS Spectrums , Volume 27 , Issue 5 , October 2022 , pp. 570 - 587
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Olfson, M, Blanco, C, Liu, SM, et al. National trends in the office-based treatment of children, adolescents, and adults with antipsychotics. Arch Gen Psychiatry. 2012;69(12):1247–1256.CrossRefGoogle ScholarPubMed
Kalverdijk, LJ, Bachmann, CJ, Aagaard, L, et al. A multi-national comparison of antipsychotic drug use in children and adolescents, 2005–2012. Child Adolesc Psychiatry Ment Health. 2017;11:55 Google Scholar
Karanges, EA, Stephenson, CP, McGregor, IS. Longitudinal trends in the dispensing of psychotropic medications in Australia from 2009–2012: focus on children, adolescents and prescriber specialty. Aust N Z J Psychiatry. 2014;48(10):917–931.CrossRefGoogle ScholarPubMed
Bachmann, CJ, Lempp, T, Glaeske, G, et al. Antipsychotic prescription in children and adolescents: an analysis of data from a German statutory health insurance company from 2005 to 2012. Dtsch Arztebl. 2014;111(3):25–34.Google ScholarPubMed
Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002;347(5):314–321.CrossRefGoogle Scholar
Research Units on Pediatric Psychopharmacology Autism Network. Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology. Am J Psychiatry. 2005;162(6):1142–1148.CrossRefGoogle Scholar
Correll, CU, Joan, Z, William, C, et al. Early antipsychotic response to aripiprazole in adolescents with schizophrenia: predictive value for clinical outcomes. J Am Acad Child Adolesc Psychiatry. 2013;52(7):689–698.CrossRefGoogle ScholarPubMed
Haas, M, Delbello, MP, Pandina, G, et al. Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: a randomized, double-blind, placebo-controlled study. Bipolar Disord. 2009;11(7):687–700.CrossRefGoogle ScholarPubMed
Findling, RL. Atypical antipsychotic treatment of disruptive behavior disorders in children and adolescents. J Clin Psychiatry. 2008;69(Suppl 4):9–14.Google ScholarPubMed
Matsumoto, H, Ishigooka, J, Ono, H, et al. (2018) Safety and efficacy from a 6-week double-blind study and a 52-week open-label extension of aripiprazole in adolescents with schizophrenia in Japan. Psychiatry Clin Neurosci. 2018;72(9):701–712.Google Scholar
Sporn, AL, Vermani, A, Greenstein, DK, et al. Clozapine treatment of childhood-onset schizophrenia: evaluation of effectiveness, adverse effects, and long-term outcome. J Am Acad Child Adolesc Psychiatry. 2007;46(10):1349–1356.CrossRefGoogle ScholarPubMed
Katagiri, H, Tohen, M, McDonnell, DP, et al. Safety and efficacy of olanzapine in the long-term treatment of Japanese patients with bipolar I disorder, depression: an integrated analysis. Psychiatry Clin Neurosci. 2014;68(7):498–505.CrossRefGoogle ScholarPubMed
Anderson, GM, Scahill, L, McCracken, JT, et al. Effects of short- and long-term risperidone treatment on prolactin levels in children with autism. Biol Psychiatry. 2007;61(4):545–550.CrossRefGoogle Scholar
McQuire, C, Hassiotis, A, Harrison, B, et al. Pharmacological interventions for challenging behavior in children with intellectual disabilities: a systematic review and meta-analysis. BMC Psychiatry. 2015;15:303 CrossRefGoogle ScholarPubMed
Wei, YJ, Liu, X, Rao, N, et al. Physical health outcomes in preschoolers with prior authorization for antipsychotics. J Child Adolesc Psychopharmacol. 2017;27(9):833–839.Google ScholarPubMed
Zuddas, A, Di Martino, A, Muglia, P, et al. Long-term risperidone for pervasive developmental disorder: efficacy, tolerability, and discontinuation. J Child Adolesc Psychopharmacol. 2000;10(2):79–90.CrossRefGoogle ScholarPubMed
Miklowitz, DJ, Schneck, CD, George, EL, et al. Pharmacotherapy and family-focused treatment for adolescents with bipolar I and II disorders: a 2-year randomized trial. Am J Psychiatry. 2014;171(6):658–667.CrossRefGoogle ScholarPubMed
Noguera, A, Ballesta, P, Baeza, I, et al. Twenty-four months of antipsychotic treatment in children and adolescents with first psychotic episode: discontinuation and tolerability. J Clin Psychopharmacol. 2013;33(4):463–471.CrossRefGoogle ScholarPubMed
Marcus, RN, Owen, R, Manos, G, et al. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study. J Clin Psychiatry. 2011;72(9):1270–1276.CrossRefGoogle ScholarPubMed
Malone, RP, Maislin, G, Choudhury, MS, et al. Risperidone treatment in children and adolescents with autism: short- and long-term safety and effectiveness. J Am Acad Child Adolesc Psychiatry. 2002;41(2):140–147.CrossRefGoogle Scholar
Gulisano, M, Calì, PV, Cavanna, AE, et al. Cardiovascular safety of aripiprazole and pimozide in young patients with Tourette syndrome. Neurol Sci. 2011;32(6):1213–1217.CrossRefGoogle ScholarPubMed
Haas, M, Karcher, K, Pandina, GJ. Treating disruptive behavior disorders with risperidone: a 1-year, open-label safety study in children and adolescents. J Child Adolesc Psychopharmacol. 2008;18(4):337–345.CrossRefGoogle ScholarPubMed
Gencer, O, Emiroglu, FN, Miral, S, et al. Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder. An open label maintenance study. Eur Child Adolesc Psychiatry. 2008;17:217–225.CrossRefGoogle ScholarPubMed
Migliardi, G, Spina, E, D’Arrigo, C, et al. Short- and long-term effects on prolactin of risperidone and olanzapine treatments in children and adolescents. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(8):1496–1501.CrossRefGoogle Scholar
Findling, RL, Reed, MD, O’Riordan, MA, et al. A 26-week open-label study of quetiapine in children with conduct disorder. J Child Adolesc Psychopharmacol. 2007;17(1):1–9.CrossRefGoogle ScholarPubMed
Croonenberghs, J, Fegert, JM, Findling, RL, et al. Risperidone in children with disruptive behavior disorders and subaverage intelligence: a 1-year, open-label study of 504 patients. J Am Acad Child Adolesc Psychiatry. 2005;44(1):64–72.CrossRefGoogle ScholarPubMed
McConville, B, Carrero, L, Sweitzer, D, et al. Long-term safety, tolerability, and clinical efficacy of quetiapine in adolescents: an open-label extension trial. J Child Adolesc Psychopharmacol. 2003;13(1):75–82.CrossRefGoogle Scholar
Canitano, R. Clinical experience with Topiramate to counteract neuroleptic induced weight gain in 10 individuals with autistic spectrum disorders. Brain Dev. 2005;27(3):228–232.CrossRefGoogle ScholarPubMed
Higgins, JPT, Green, S. Analysing data and undertaking meta-analyses. In: Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, Version 5.2.0; 2011.Google Scholar
PROSPERO. International Prospective Register of Systematic Reviews. Centre for Reviews and Dissemination, University of York, United Kingdom. www.crd.york.ac.uk/prospero.Google Scholar
RevMan. The Cochrane Collaboration, Version 5.3; 2014.Google Scholar
Higgins, JPT, Green, S. Chapter 9: summarizing study characteristics and preparing for synthesis. In: Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, Version 5.2.0; 2011:1–61.Google Scholar
Higgins, JPT, Green, S. Chapter 8: assessing risk of bias in included studies. In: Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, Version 5.2.0; 2011:1–72.Google Scholar
Findling, RL, Correll, CU, Nyilas, M, et al. Aripiprazole for the treatment of pediatric bipolar I disorder: a 30-week, randomized placebo-controlled study. Bipolar Disord. 2013;15(2):138–149.CrossRefGoogle ScholarPubMed
Findling, RL, Townsend, L, Bown, NV, et al. The treatment of severe childhood aggression study: 12 weeks of extended, blinded treatment in clinical responders. J Child Adolesc Psychopharmacol. 2017;27(1):52–65.CrossRefGoogle ScholarPubMed
Findling, RL, Youngstrom, EA, McNamara, NK, et al. Double-blind randomized, placebo-controlled long-term maintenance study of aripiprazole in children with bipolar disorder. J Clin Psychiatry. 2012;73(1):57–63.Google ScholarPubMed
Findling, RL, Mankoski, R, Timko, K, et al. A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder. J Clin Psychiatry. 2014;75(1):22–30.CrossRefGoogle ScholarPubMed
Correll, UC, Kohegyi, E, Zhao, C, et al. (2017) Oral aripiprazole as maintenance treatment in adolescent schizophrenia: results from a 52-week, randomized, placebo-controlled withdrawal study. J Am Acad Child Adolesc Psychiatry. 2017;56(9):784–792.CrossRefGoogle ScholarPubMed
Reyes, M, Buitelaar, J, Toren, P, et al. Double-blind, placebo-controlled study of risperidone maintenance treatment in children and adolescents with disruptive behavior disorder. Am J Psychiatry. 2006;163(3):402–410.CrossRefGoogle Scholar
Pandina, GJ, Zhu, Y, Cornblatt, B. Cognitive function with long-term risperidone in children and adolescents with disruptive behavior disorder. J Child Adolesc Psychopharmacol. 2009;19(6):749–756.CrossRefGoogle ScholarPubMed
Tanner, JM, Whitehouse, RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child. 1976;51(3):170–179.CrossRefGoogle ScholarPubMed
Marshall, WA, Tanner, JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291–303.Google Scholar
Marshall, WA, Tanner, JM. Variation in the pattern of pubertal changes in boys. Arch Dis Child. 1970;45(239):13–23.CrossRefGoogle Scholar
Le, J, Feygin, Y, Creel, L, et al. Trends in diagnosis of bipolar and disruptive mood dysregulation disorders in children and youth. J Affect Disord. 2020;264:242–248.CrossRefGoogle ScholarPubMed
Nicol, GE, Yingling, MD, Flavin, KS, et al. Metabolic effects of antipsychotics on adiposity and insulin sensitivity in youths: a randomized clinical trial. JAMA Psychiatry. 2018;75(8):788–796.CrossRefGoogle ScholarPubMed
Kleinberg, DL, Davis, JM, De Coster, R, et al. Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychopharmacol. 1999;19(5):57–61.CrossRefGoogle ScholarPubMed
Kishimoto, T, Watanabe, K, Shimada, N, et al. Antipsychotic-induced hyperprolactinemia inhibits the hypothalamo–pituitary–gonadal axis and reduces bone mineral density in male patients with schizophrenia. J Clin Psychiatry. 2008;69(3):385–391.CrossRefGoogle ScholarPubMed
Aman, MG, De Smedt, G, Derivan, A, et al. Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence. Am J Psychiatry. 2002;159(8):1337–1346.CrossRefGoogle ScholarPubMed
Marcus, RN, Owen, R, Kamen, L, et al. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry. 2009;48:1110–1119.CrossRefGoogle ScholarPubMed
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