Skip to main content

Advertisement

Log in

Use of Antipsychotic Drugs for Psychotic Disorders in Children

  • Schizophrenia and Other Psychotic Disorders (J Csernansky, Section Editor)
  • Published:
Current Treatment Options in Psychiatry Aims and scope Submit manuscript

Abstract

Purpose of review

This review aims to provide evidence-based guidance regarding the use of antipsychotic medications for treatment of children and adolescents with psychotic disorders. Research findings from the past 3 years are emphasized.

Recent findings

A number of studies have demonstrated the efficacy of antipsychotic medications for use in children and/or adolescents with psychotic disorders, but there is also high potential for significant side effects. Atypical antipsychotic drugs are often preferred instead of typical antipsychotics due to reduced risk of extrapyramidal symptoms, but the risk for weight gain and metabolic side effects is a particular concern with atypical antipsychotic drugs. Several antipsychotics are now FDA approved for the treatment of schizophrenia in the pediatric population, including the atypical antipsychotics aripiprazole, lurasidone, olanzapine, paliperidone, quetiapine, and risperidone. Although clozapine is not FDA approved for use in the pediatric population, and children may be more susceptible to serious side effects from this medication, studies have demonstrated its efficacy in treating early-onset schizophrenia. A recently reported rare but potentially serious side effect of the third-generation antipsychotic aripiprazole is new-onset impulse control symptoms (such as compulsive gambling and sexual urges), but there is not enough information available to show whether this particular adverse event is as common in children as in adults.

Summary

Although the use of antipsychotic drugs is appropriate to control symptoms of early-onset primary psychotic disorders, the potential for medically significant side effects from these drugs warrants a need for careful diagnostic evaluation prior to starting antipsychotics in children, followed by careful monitoring and management of adverse events that may occur during treatment. Further research is needed to determine the relative efficacy of treatment options, investigate the value of polypharmacy, and develop methods of preventing and managing adverse effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Olfson M, Crystal S, Huang C, Gerhard T. Trends in antipsychotic drug use by very young, privately insured children. J Am Acad Child Adolesc Psychiatry. 2010;49(1):13–23.

    PubMed  Google Scholar 

  2. Kalverdijk LJ, Bachmann CJ, Aagaard L, Burcu M, Glaeske G, Hoffmann F, et al. Multi-national comparison of antipsychotic drug use in children and adolescents, 2005-2012. Child Adolesc Psychiatry Ment Health. 2017;11(1):55. https://doi.org/10.1186/s13034-017-0192-1.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Olfson M, Blanco C, Liu L, Moreno C. National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. Arch Gen Psychiatry. 2006;63(6):679–85. https://doi.org/10.1001/archpsyc.63.6.679.

    Article  PubMed  Google Scholar 

  4. •• Kranzler HN, Cohen SD. Psychopharmacological treatment of psychosis in children and adolescents: efficacy and management. Child Adolesc Psychiatric Clin N Am. 2013;22(4):727–744.This review includes useful tables comparing risk for specific side effects among various first, second, and third generation antipsychotics. The article also includes information regarding drug interactions, methods of side effect monitoring (including a tracking sheet which can be copied and kept in patient charts), and recommendations regarding actions to take when serious adverse effects occur. https://doi.org/10.1016/j.chc.2013.06.002.

    Article  Google Scholar 

  5. Harrison JN, Cluxton-Keller F, Gross D. Antipsychotic medication prescribing trends in children and adolescents. J Pediatr Health Care. 2012;26(2):139–45. https://doi.org/10.1016/j.pedhc.2011.10.009.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zito JM, Derivan AT, Kratochvil CJ, Safer DJ, Fegert JM, Greenhill LL. Off-label psychopharmacologic prescribing for children: history supports close clinical monitoring. Child Adolesc Psychiatry Ment Health. 2008;2(1):24. https://doi.org/10.1186/1753-2000-2-24.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Blader JC. Acute inpatient care for psychiatric disorders in the United States, 1996 through 2007. Arch Gen Psychiatry. 2011;68(12):1276–83. https://doi.org/10.1001/archgenpsychiatry.2011.84.

    Article  PubMed  Google Scholar 

  8. Gallego JA, Bonetti J, Zhang J, Kane JM, Correll CU. Prevalence and correlates of antipsychotic polypharmacy from the 1970s to 2009: a systematic review and meta regression. Schizophr Res. 2012;138(1):18–28. https://doi.org/10.1016/j.schres.2012.03.018.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Barnes TR, Paton C. Antipsychotic polypharmacy in schizophrenia: benefits and risks. CNS Drugs. 2011;25(5):383–99. https://doi.org/10.2165/11587810-000000000-00000.

    Article  PubMed  Google Scholar 

  10. Constantine RJ, Boaz T, Tandon R. Antipsychotic polypharmacy in the treatment of children and adolescents in the fee-for-service component of a large state Medicaid program. Clin Ther. 2010;32(5):949–59. https://doi.org/10.1016/j.clinthera.2010.04.021.

    Article  PubMed  Google Scholar 

  11. Noguera A, Ballesta P, Baeza I, Arango C, de la Serna E, González-Pinto A, 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):463–71. https://doi.org/10.1097/JCP.0b013e3182962480.

    Article  CAS  PubMed  Google Scholar 

  12. Patel NC, Crismon ML, Hoagwood K, Johnsrud MT, Rascati KL, Wilson JP, et al. Trends in the use of typical and atypical antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2005;44(6):548–56. https://doi.org/10.1097/01.chi.0000157543.74509.c8.

    Article  PubMed  Google Scholar 

  13. Crystal S, Olfson M, Huang C, Pincus H, Gerhard T. Broadened use of atypical antipsychotics: safety, effectiveness, and policy challenges. Health Aff (Millwood). 2009;28(5):w770–81. https://doi.org/10.1377/hlthaff.28.5.w770.

    Article  Google Scholar 

  14. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013. https://doi.org/10.1176/appi.books.9780890425596.

    Book  Google Scholar 

  15. •• Driver DI, Gogtay N, Rapoport JL. Childhood onset schizophrenia and early onset schizophrenia spectrum disorders. Child Adolesc Psychiatr Clin N Am. 2013;22(4):539–555.This is an excellent review on the topic of childhood onset schizophrenia (cases with onset prior to age 13 years), based largely on observations made during a large NIMH study. https://doi.org/10.1016/j.chc.2013.04.001.

    Article  PubMed  PubMed Central  Google Scholar 

  16. • Benjamin S, Lauterbach MD, Stanislawski AL. Congenital and acquired disorders presenting as psychosis in children and young adults. Child Adolesc Psychiatr Clin N Am. 2013;22(4):581–608.This article describes medical work-up for psychosis in youth, and includes an extensive list of medical disorders that may lead to psychotic symptoms. https://doi.org/10.1016/j.chc.2013.04.004.

    Article  PubMed  Google Scholar 

  17. Norman RM, et al. The role of treatment delay in predicting 5-year outcomes in an early intervention program. Psychol Med. 2011;42:1–11.

    Google Scholar 

  18. Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry. 2005;162(10):1785–804. https://doi.org/10.1176/appi.ajp.162.10.1785.

    Article  PubMed  Google Scholar 

  19. • James AC. Prescribing antipsychotics for children and adolescents. Adv Psychiatr Treat 2010; 16 (1) 63–75, Available at http://apt.rcpsych.org/content/16/1/63 , Accessed 11/19/2017. This review includes a useful table showing risk for various side effects among several atypical antipsychotics and haloperidol. DOI: https://doi.org/10.1192/apt.bp.108.005652.

  20. https://dailymed.nlm.nih.gov/dailymed/index.cfm, Accessed on 19 Nov 2017.

  21. https://www.goodrx.com/, Accessed on 19 Nov 2017.

  22. •• https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm, Accessed on 19 Nov 2017. This FDA website is an excellent source for looking up current full prescribing information (product labels) and other useful information about FDA-approved medications.

  23. https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders, Accessed on 19 Nov 2017.

  24. • Maloney AE, Yakutis LJ, Frazier JA. Empirical evidence for psychopharmacologic treatment in early-onset psychosis and schizophrenia. Child Adolesc Psychiatr Clin N Am. 2012;21(4):885–909.This article includes an extensive review of antipsychotic treatment trials for pediatric schizophrenia spectrum disorders occurring between 1967 and 2011. https://doi.org/10.1016/j.chc.2012.07.011.

    Article  PubMed  Google Scholar 

  25. Kumra S, Frazier JA, Jacobsen LK, McKenna K, Gordon CT, Lenane MC, et al. Childhood-onset schizophrenia. A double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry. 1996;53(12):1090–7. https://doi.org/10.1001/archpsyc.1996.01830120020005.

    Article  CAS  PubMed  Google Scholar 

  26. Shaw P, Sporn A, Gogtay N, Overman GP, Greenstein D, Gochman P, et al. Childhood-onset schizophrenia: a double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry. 2006;63(7):721–30. https://doi.org/10.1001/archpsyc.63.7.721.

    Article  CAS  PubMed  Google Scholar 

  27. Fleischhaker C, Heiser P, Hennighausen K, Herpertz-Dahlmann B, Holtkamp K, Mehler-Wex C, et al. Weight gain associated with clozapine, olanzapine and risperidone in children and adolescents. J Neural Transm (Vienna). 2007;114(6):273–80. https://doi.org/10.1007/s00702-006-0602-7.

    Article  CAS  Google Scholar 

  28. Sikich L, Frazier JA, McClellan J, Findling RL, Vitiello B, Ritz L, et al. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry. 2008;165(11):1420–31. https://doi.org/10.1176/appi.ajp.2008.08050756.

    Article  PubMed  Google Scholar 

  29. Findling RL, Johnson JL, McClellan J, Frazier JA, Vitiello B, Hamer RM, et al. Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study. J Am Acad Child Adolesc Psychiatry. 2010;49(6):583–94. https://doi.org/10.1016/j.jaac.2010.03.013.

    PubMed  PubMed Central  Google Scholar 

  30. De Hert M, Dobbelaere M, Sheridan EM, Cohen D, Correll CU. Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: a systematic review of randomized, placebo controlled trials and guidelines for clinical practice. Eur Psychiatry. 2011;26(3):144–58. https://doi.org/10.1016/j.eurpsy.2010.09.011.

    Article  PubMed  Google Scholar 

  31. Fraguas D, Correll CU, Merchán-Naranjo J, Rapado-Castro M, Parellada M, Moreno C, et al. Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: comprehensive review of prospective head-to-head and placebo-controlled comparisons. Eur Neuropsychopharmacol. 2011;21(8):621–45. https://doi.org/10.1016/j.euroneuro.2010.07.002.

    Article  CAS  PubMed  Google Scholar 

  32. Cohen D, Bonnot O, Bodeau N, Consoli A, Laurent C. Adverse effects of second-generation antipsychotics in children and adolescents: a Bayesian meta-analysis. J Clin Psychopharmacol. 2012;32(3):309–16. https://doi.org/10.1097/JCP.0b013e3182549259.

    Article  CAS  PubMed  Google Scholar 

  33. •• Harvey RC, James AC, Shields GE. A systematic review and network meta-analysis to assess the relative efficacy of antipsychotics for the treatment of positive and negative symptoms in early-onset schizophrenia. CNS Drugs. 2016;30(1):27–39.This recent review of EOS trials compares the effects of several different antipsychotics on positive, negative, and total symptoms. https://doi.org/10.1007/s40263-015-0308-1.

    Article  CAS  PubMed  Google Scholar 

  34. •• Pagsberg AK, Tarp S, Glintborg D, Stenstrøm AD, Fink-Jensen A, Correll CU, et al. Acute antipsychotic treatment of children and adolescents with schizophrenia-spectrum disorders: a systematic review and network meta-analysis. J Am Acad Child Adolesc Psychiatry. 2017;56(3):191–202.This recent review compares efficacy and side effects among several antipsychotics used for the acute treatment of schizophrenia spectrum disorders in children and adolescents. It includes a useful summary table that can be helpful in choosing an antipsychotic based on efficacy and side effect profile. https://doi.org/10.1016/j.jaac.2016.12.013.

    Article  PubMed  Google Scholar 

  35. • Correll CU. From receptor pharmacology to improved outcomes: individualising the selection, dosing, and switching of antipsychotics. Eur Psychiatry. 2010;25(Suppl 2):S12–S21.This article describes useful strategies for antipsychotic switching. https://doi.org/10.1016/S0924-9338(10)71701-6.

    Article  PubMed  Google Scholar 

  36. http://switchrx.ca/ Accessed on 22 Nov 2017. This website provides medication-specific suggested cross-tapering schedules to use when switching from one psychotropic medication to another.

  37. • Montejo ÁL, Arango C, Bernardo M, Carrasco JL, Crespo-Facorro B, Cruz JJ, et al. Multidisciplinary consensus on the therapeutic recommendations for iatrogenic hyperprolactinemia secondary to antipsychotics. Front Neuroendocrinol. 2017;45:25–34.This article provides guidance regarding the management of antipsychotic-induced hyperprolactinemia. https://doi.org/10.1016/j.yfrne.2017.02.003.

    Article  CAS  PubMed  Google Scholar 

  38. Almandil NB, Liu Y, Murray ML, Besag FMC, Aitchison KJ, Wong ICK. Weight gain and other metabolic adverse effects associated with atypical antipsychotic treatment of children and adolescents: a systematic review and meta-analysis. Paediatric Drugs. 2013;15(2):139–50. https://doi.org/10.1007/s40272-013-0016-6.

    Article  PubMed  Google Scholar 

  39. Solmi M, Murru A, Pacchiarotti I, Undurraga J, Veronese N, Fornaro M, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017;13:757–77. https://doi.org/10.2147/TCRM.S117321.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mahapatra A, Sharma P, Sagar R. Aripiprazole induced impulse control disorders: where do we stand? Asian J Psychiatr. 2016;23:128–30. https://doi.org/10.1016/j.ajp.2016.08.001.

    Article  PubMed  Google Scholar 

  41. • Etminan M, Sodhi M, Samii A, Procyshyn RM, Guo M, Carleton BC. Risk of gambling disorder and impulse control disorder with aripiprazole, pramipexole, and ropinirole: a pharmacoepidemiologic study. J Clin Psychopharmacol. 2017;37(1):102–104.This article examines epidemiological evidence suggesting increased risk of impulse control disorders in patients taking dopamine agonists (including aripiprazole, pramipexole and ropinirole). https://doi.org/10.1097/JCP.0000000000000634.

    Article  CAS  PubMed  Google Scholar 

  42. Clozapine REMS Program 2017, https://www.clozapinerems.com, Accessed 22 Nov 2017.

  43. Schulz E, Fleischhaker C, Remschmidt HE. Correlated changes in symptoms and neurotransmitter indices during maintenance treatment with clozapine or conventional neuroleptics in adolescents and young adults with schizophrenia. J Child Adolesc Psychopharmacol. 1996;6(2):119–31. https://doi.org/10.1089/cap.1996.6.119.

    Article  CAS  PubMed  Google Scholar 

  44. Findling RL, Cavuş I, Pappadopulos E, Vanderburg DG, Schwartz JH, Gundapaneni BK, et al. Ziprasidone in adolescents with schizophrenia: results from a placebo-controlled efficacy and long-term open-extension study. J Child Adolesc Psychopharmacol. 2013;23(8):531–44. https://doi.org/10.1089/cap.2012.0068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27:596–601.

    Article  Google Scholar 

  46. McClellan J, Stock S, American Academy of Child and Adolescent Psychiatry (AACAP), Committee on Quality Issues (CQI). Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry. 2013;52(9):976–90. https://doi.org/10.1016/j.jaac.2013.02.008.

    Article  PubMed  Google Scholar 

  47. Maayan L, Vakhrusheva J, Correll CU. Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Neuropsychopharmacology. 2010;35(7):1520–30. https://doi.org/10.1038/npp.2010.21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Anagnostou E, Aman MG, Handen BL, Sanders KB, Shui A, Hollway JA, et al. Metformin for treatment of overweight induced by atypical antipsychotic medication in young people with autism spectrum disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73(9):928–37. https://doi.org/10.1001/jamapsychiatry.2016.1232.

    Article  PubMed  Google Scholar 

  49. Handen BL, Anagnostou E, Aman MG, Sanders KB, Chan J, Hollway JA, et al. A randomized, placebo-controlled trial of metformin for the treatment of overweight induced by antipsychotic medication in young people with autism spectrum disorder: open-label extension. J Am Acad Child Adolesc Psychiatry. 2017;56(10):849–856.e6. https://doi.org/10.1016/j.jaac.2017.07.790.

    Article  PubMed  Google Scholar 

  50. Mostafavi SA, Solhi M, Mohammadi MR, Akhondzadeh S. Melatonin for reducing weight gain following Administration of Atypical Antipsychotic Olanzapine for adolescents with bipolar disorder: arandomized, double-blind, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2017;27(5):440–4. https://doi.org/10.1089/cap.2016.0046.

    Article  CAS  PubMed  Google Scholar 

  51. Nicol G, Worsham E, Haire-Joshu D, Duncan A, Schweiger J, Yingling M, et al. Getting to more effective weight management in antipsychotic-treated youth: a survey of barriers and preferences. Child Obes. 2016;12(1):70–6. https://doi.org/10.1089/chi.2015.0076.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Nicol GE, Kolko RP, Mills M, Gunnarsdottir T, Yingling MD, Schweiger JA, et al. Behavioral weight loss treatment in antipsychotic treated youth. Scand J Child Adolesc Ps7ychiatr Psychol. 2016;4(2):96–104.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Angela M. Reiersen MD, MPE.

Ethics declarations

Conflict of Interest

Shahana Ayub declares that she has no conflict of interest. Ujjwal P. Ramtekkar declares that he has no conflict of interest. Angela M. Reiersen declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

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

Additional information

This article is part of the Topical Collection on Schizophrenia and Other Psychotic Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ayub, S., Ramtekkar, U.P. & Reiersen, A.M. Use of Antipsychotic Drugs for Psychotic Disorders in Children. Curr Treat Options Psych 5, 30–55 (2018). https://doi.org/10.1007/s40501-018-0137-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40501-018-0137-1

Keywords

Navigation