Skip to main content
SpringerLink
Log in

The Safety of Olanzapine in Young Children: A Systematic Review and Meta-Analysis

  • Systematic Review
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Background

Olanzapine is frequently prescribed in young children for psychiatric conditions. It may be an option for chemotherapy-induced nausea and vomiting (CINV) control in children. The objective of this review was to describe the safety of olanzapine in children less than 13 years of age to determine if safety concerns would be a barrier to its use for CINV prevention.

Methods

Electronic searches were performed in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Scopus. All studies in English reporting adverse effects associated with olanzapine use in children younger than 13 years or with a mean/median age less than 13 years were included. Adverse outcomes were synthesized for prospective studies.

Results

A total of 47 studies (17 prospective) involving 387 children aged 0.6–18 years were included; nine described olanzapine poisonings. Weight gain or sedation were reported in 78 % [95 % confidence interval (CI) 63–95] and 48 % (95 % CI 35–67), respectively. Extrapyramidal symptoms or electrocardiogram abnormalities were reported in 9 % (95 % CI 4–21) and 14 % (95 % CI 7–26), respectively. Elevation in liver function tests or blood glucose abnormalities were reported in 7 % (95 % CI 2–20) and 4 % (95 % CI 1–17), respectively. No deaths were attributed to olanzapine.

Limitations

No studies were identified with a primary focus on evaluating safety, and the adverse effects reported in the included studies were heterogeneous.

Conclusions

Most adverse events associated with olanzapine use in children less than 13 years of age are of minor clinical significance. These findings support the exploration of olanzapine for the prevention of CINV in children in future trials.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cheng-Shannon J, McGough JJ, Pataki C, McCracken JT. Second-generation antipsychotic medications in children and adolescents. J Child Adolesc Psychopharmacol. 2004;14(3):372–94.

    Article  PubMed  Google Scholar 

  2. 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 00004583-201001000-00005 [pii].

    PubMed  Google Scholar 

  3. Pfeifer JC, Kowatch RA, DelBello MP. Pharmacotherapy of bipolar disorder in children and adolescents: recent progress. CNS Drugs. 2010;24(7):575–93. doi:10.2165/11533110-000000000-00000.

    Article  PubMed  CAS  Google Scholar 

  4. Masi G. Pharmacotherapy of pervasive developmental disorders in children and adolescents. CNS Drugs. 2004;18(14):1031–52.

    Article  PubMed  CAS  Google Scholar 

  5. Eli Lilly and Company. Zyprexa prescribing information. Indianapolis: Eli Lilly and Co.; 2010.

    Google Scholar 

  6. 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. Paediatr Drugs. 2013;15(2):139–50. doi:10.1007/s40272-013-0016-6.

    Article  PubMed  Google Scholar 

  7. 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. doi:10.1097/JCP.0b013e3182549259.

    Article  PubMed  CAS  Google Scholar 

  8. Norris ML, Spettigue W, Buchholz A, Henderson KA, Gomez R, Maras D, et al. Olanzapine use for the adjunctive treatment of adolescents with anorexia nervosa. J Child Adolesc Psychopharmacol. 2011;21(3):213–20. doi:10.1089/cap.2010.0131.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Navari R, Gray S, Kerr A. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV): a randomized phase III trial. [abstract]. J Clin Oncol. 2010;28:641s.

    Article  Google Scholar 

  10. Navari RM, Nagy CK, Gray SE. The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. Support Care Cancer. 2013;21(6):1655–63. doi:10.1007/s00520-012-1710-6.

    Article  PubMed  Google Scholar 

  11. Navari RM, Einhorn LH, Loehrer PJ Sr, Passik SD, Vinson J, McClean J, et al. A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier oncology group study. Support Care Cancer. 2007;15(11):1285–91.

    Article  PubMed  Google Scholar 

  12. Passik SD, Kirsh KL, Theobald DE, Dickerson P, Trowbridge R, Gray D, et al. A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients. J Pain Sympt Manag. 2003;25(5):485–8.

    Article  Google Scholar 

  13. Hocking CM, Kichenadasse G. Olanzapine for chemotherapy-induced nausea and vomiting: a systematic review. Support Care Cancer. 2014;22(4):1143–51. doi:10.1007/s00520-014-2138-y.

    Article  PubMed  Google Scholar 

  14. Dupuis LL, Boodhan S, Holdsworth M, Robinson PD, Hain R, Portwine C, et al. Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2013;60:1073–82.

    Article  PubMed  Google Scholar 

  15. Dupuis LL, Milne-Wren C, Cassidy M, Barrera M, Portwine C, Johnston DL, et al. Symptom assessment in children receiving cancer therapy: the parents’ perspective. Support Care Cancer. 2010;18(3):281–99. doi:10.1007/s00520-009-0651-1.

    Article  PubMed  Google Scholar 

  16. Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Annal Intern Med. 2013;158(4):280–6.

    Article  Google Scholar 

  17. Hollander E, Wasserman S, Swanson EN, Chaplin W, Schapiro ML, Zagursky K, et al. A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder. J Child Adolesc Psychopharmacol. 2006;16(5):541–8.

    Article  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. Wozniak J, Mick E, Waxmonsky J, Kotarski M, Hantsoo L, Biederman J. Comparison of open-label, 8-week trials of olanzapine monotherapy and topiramate augmentation of olanzapine for the treatment of pediatric bipolar disorder. J Child Adolesc Psychopharmacol. 2009;19(5):539–45. doi:10.1089/cap.2009.0042.

    Article  PubMed  Google Scholar 

  20. McCracken JT, Suddath R, Chang S, Thakur S, Piacentini J. Effectiveness and tolerability of open label olanzapine in children and adolescents with Tourette syndrome. J Child Adolesc Psychopharmacol. 2008;18(5):501–8. doi:10.1089/cap.2007.135.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Fido A, Al-Saad S. Olanzapine in the treatment of behavioral problems associated with autism: an open-label trial in Kuwait. Med Princ Pract. 2008;17(5):415–8. doi:10.1159/000141508.

    Article  PubMed  Google Scholar 

  22. Quintana H, Wilson MS 2nd, Purnell W, Layman AK, Mercante D. An open-label study of olanzapine in children and adolescents with schizophrenia. J Psychiatr Pract. 2007;13(2):86–96.

    Article  PubMed  Google Scholar 

  23. Milin R, Simeon JG, Batth S, Thatte S, Dare GJ, Walker S. An open trial of olanzapine in children and adolescents with Asperger disorder. J Clin Psychopharmacol. 2006;26(1):90–2.

    Article  PubMed  CAS  Google Scholar 

  24. Mozes T, Ebert T, Michal S-E, Spivak B, Weizman A. An open-label randomized comparison of olanzapine versus risperidone in the treatment of childhood-onset schizophrenia. J Child Adolesc Psychopharmacol. 2006;16(4):393–403.

    Article  PubMed  Google Scholar 

  25. Biederman J, Mick E, Hammerness P, Harpold T, Aleardi M, Dougherty M, et al. Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children. Biol Psychiatry. 2005;58(7):589–94.

    Article  PubMed  CAS  Google Scholar 

  26. Stephens RJ, Bassel C, Sandor P. Olanzapine in the treatment of aggression and tics in children with Tourette’s syndrome—a pilot study. J Child Adolesc Psychopharmacol. 2004;14(2):255–66.

    Article  PubMed  Google Scholar 

  27. Mozes T, Greenberg Y, Spivak B, Tyano S, Weizman A, Mester R. Olanzapine treatment in chronic drug-resistant childhood-onset schizophrenia: an open-label study. J Child Adolesc Psychopharmacol. 2003;13(3):311–7.

    Article  PubMed  Google Scholar 

  28. Ross RG, Novins D, Farley GK, Adler LE. A 1-year open-label trial of olanzapine in school-age children with schizophrenia. J Child Adolesc Psychopharmacol. 2003;13(3):301–9.

    Article  PubMed  Google Scholar 

  29. Kemner C, Willemsen-Swinkels SHN, de Jonge M, Tuynman-Qua H, van Engeland H. Open-label study of olanzapine in children with pervasive developmental disorder. J Clin Psychopharmacol. 2002;22(5):455–60.

    Article  PubMed  CAS  Google Scholar 

  30. Frazier JA, Biederman J, Tohen M, Feldman PD, Jacobs TG, Toma V, et al. A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder. J Child Adolesc Psychopharmacol. 2001;11(3):239–50.

    Article  PubMed  CAS  Google Scholar 

  31. Malone RP, Cater J, Sheikh RM, Choudhury MS, Delaney MA. Olanzapine versus haloperidol in children with autistic disorder: an open pilot study. J Am Acad Child Adolesc Psychiatry. 2001;40(8):887–94.

    Article  PubMed  CAS  Google Scholar 

  32. Sholevar EH, Baron DA, Hardie TL. Treatment of childhood-onset schizophrenia with olanzapine. J Child Adolesc Psychopharmacol. 2000;10(2):69–78.

    Article  PubMed  CAS  Google Scholar 

  33. Sethi S, Setiya R, Lallar K. Successful treatment of Sydenham chorea with olanzapine. J Pediatric Neurol. 2006;4(3):171–4.

    CAS  Google Scholar 

  34. Turkel SB, Jacobson J, Munzig E, Tavare CJ. Atypical antipsychotic medications to control symptoms of delirium in children and adolescents. J Child Adolesc Psychopharmacol. 2012;22(2):126–30. doi:10.1089/cap.2011.0084.

    Article  PubMed  CAS  Google Scholar 

  35. Turkel SB, Jacobson JR, Tavare CJ. The diagnosis and management of delirium in infancy. J Child Adolesc Psychopharmacol. 2013;23(5):352–6. doi:10.1089/cap.2013.0001.

    Article  PubMed  CAS  Google Scholar 

  36. Bengi Semerci Z. Olanzapine in Tourette’s disorder. J Am Acad Child Adolesc Psychiatry. 2000;39(2):140.

    Article  PubMed  CAS  Google Scholar 

  37. Bozkurt H, Mukaddes NM. Catatonia in a child with autistic disorder. Turk J Pediatr. 2010;52(4):435–8.

    PubMed  Google Scholar 

  38. Ferreira Maia AP, Boarati MA, Kleinman A, Fu IL. Preschool bipolar disorder: Brazilian children case reports. J Affect Disord. 2007;104(1–3):237–43. doi:10.1016/j.jad.2007.04.003.

    Article  PubMed  Google Scholar 

  39. Emiroglu FNI, Gencer O, Ozbek A. Adjunctive olanzapine treatment in bipolar adolescents responding insufficiently to mood stabilizers. Four case reports. Eur Child Adolesc Psychiatry. 2006;15(8):500–3.

    Article  PubMed  Google Scholar 

  40. Chungh D-S, Kim B-N, Cho S-C. Neuroleptic malignant syndrome due to three atypical antipsychotics in a child. J Psychopharmacol. 2005;19(4):422–5.

    Article  PubMed  Google Scholar 

  41. Beresford C, Hepburn S, Ross RG. Schizophrenia in pre-school children: two case reports with longitudinal follow-up for 6 and 8 years. Clin Child Psychol Psychiatry. 2005;10(3):429–39. doi:10.1177/1359104505053759.

    Article  Google Scholar 

  42. Ercan ES, Kutlu A, Varan A, Cikoglu S, Coskunol H, Bayraktar E. Olanzapine treatment of eight adolescent patients with psychosis. Hum Psychopharmacol. 2004;19(1):53–6.

    Article  PubMed  CAS  Google Scholar 

  43. Courvoisie HE, Cooke DW, Riddle MA. Olanzapine-induced diabetes in a seven-year-old boy. J Child Adolesc Psychopharmacol. 2004;14(4):612–6.

    Article  PubMed  Google Scholar 

  44. Boachie A, Goldfield GS, Spettigue W. Olanzapine use as an adjunctive treatment for hospitalized children with anorexia nervosa: case reports. Int J Eat Disord. 2003;33(1):98–103.

    Article  PubMed  Google Scholar 

  45. Sheikh RM, Ahmed K. The efficacy of olanzapine, as needed, to treat acute agitation in juveniles. J Child Adolesc Psychopharmacol. 2002;12(1):71–3.

    Article  PubMed  Google Scholar 

  46. Nguyen M, Murphy T. Olanzapine and hypertriglyceridemia. J Am Acad Child Adolesc Psychiatry. 2001;40(2):133.

    Article  PubMed  CAS  Google Scholar 

  47. Mehler C, Wewetzer C, Schulze U, Warnke A, Theisen F, Dittmann RW. Olanzapine in children and adolescents with chronic anorexia nervosa. A study of five cases. Eur Child Adolesc Psychiatry. 2001;10(2):151–7.

    Article  PubMed  CAS  Google Scholar 

  48. Chang KD, Ketter TA. Mood stabilizer augmentation with olanzapine in acutely manic children. J Child Adolesc Psychopharmacol. 2000;10(1):45–9.

    Article  PubMed  CAS  Google Scholar 

  49. Lavid N, Franklin DL, Maguire GA. Management of child and adolescent stuttering with olanzapine: three case reports. Ann Clin Psychiatry. 1999;11(4):233–6.

    Article  PubMed  CAS  Google Scholar 

  50. Malek-Ahmadi P, Simonds JF. Olanzapine for autistic disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry. 1998;37(9):902.

    Article  PubMed  CAS  Google Scholar 

  51. Krishnamoorthy J, King BH. Open-label olanzapine treatment in five preadolescent children. J Child Adolesc Psychopharmacol. 1998;8(2):107–13.

    Article  PubMed  CAS  Google Scholar 

  52. Horrigan JP, Barnhill LJ, Courvoisie HE. Olanzapine in PDD. J Am Acad Child Adolesc Psychiatry. 1997;36(9):1166–7.

    Article  PubMed  CAS  Google Scholar 

  53. Taskiran S, Coffey DBJ. Unremitting impulsive aggression in a child with childhood onset schizophrenia and pervasive development disorder-not otherwise specified: the role of stimulants, atypical antipsychotics and mood stabilizers. J Child Adolesc Psychopharmacol. 2013;23(5):363–6. doi:10.1089/cap.2013.2353.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Herguner S. Excessive masturbation associated with olanzapine in a pediatric case. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(7):1349–50. doi:10.1016/j.pnpbp.2010.06.017.

    Article  PubMed  Google Scholar 

  55. Tanoshima R, Chandranipapongse W, Colantonio D, Stefan C, Nulman I. Acute olanzapine overdose in a toddler: A case report. Ther Drug Monit. 2013;. doi:10.1097/FTD.0b013e3182953ed8.

    Google Scholar 

  56. Hail SL, Obafemi A, Kleinschmidt KC. Successful management of olanzapine-induced anticholinergic agitation and delirium with a continuous intravenous infusion of physostigmine in a pediatric patient. Clin Toxicol (Phila). 2013;51(3):162–6. doi:10.3109/15563650.2013.773006.

    Article  Google Scholar 

  57. Lankheet NAG, Padberg RD, de Kluiver EM, Wilhelm AJ, van Woensel JBM, Beijnen JH, et al. Relatively mild symptoms after an olanzapine intoxication in a 2-year-old girl with excessively high serum levels. J Child Adolesc Psychopharmacol. 2011;21(1):93–5. doi:10.1089/cap.2010.0110.

    Article  PubMed  Google Scholar 

  58. Kochhar S, Nwokike JN, Jankowitz B, Sholevar EH, Abed T, Baron DA. Olanzapine overdose: a pediatric case report. J Child Adolesc Psychopharmacol. 2002;12(4):351–3.

    Article  PubMed  Google Scholar 

  59. Catalano G, Cooper DS, Catalano MC, Butera AS. Olanzapine overdose in an 18-month-old child. J Child Adolesc Psychopharmacol. 1999;9(4):267–71.

    Article  PubMed  CAS  Google Scholar 

  60. Bonin MM, Burkhart KK. Olanzapine overdose in a 1-year-old male. Pediatr Emerg Care. 1999;15(4):266–7.

    Article  PubMed  CAS  Google Scholar 

  61. Bond GR, Thompson JD. Olanzapine pediatric overdose. Ann Emerg Med. 1999;34(2):292–3.

    Article  PubMed  CAS  Google Scholar 

  62. Yip L, Dart RC, Graham K. Olanzapine toxicity in a toddler. Pediatrics. 1998;102(6):1494.

    Article  PubMed  CAS  Google Scholar 

  63. Chambers RA, Caracansi A, Weiss G. Olanzapine overdose cause of acute extrapyramidal symptoms. Am J Psychiatry. 1998;155(11):1630–1.

    PubMed  CAS  Google Scholar 

  64. Robertson MD, McMullin MM. Olanzapine concentrations in clinical serum and postmortem blood specimens—when does therapeutic become toxic? J Forensic Sci. 2000;45(2):418–21.

    PubMed  CAS  Google Scholar 

  65. Ross R, Novins D, Farley G, Adler L. A 1-year open-label trial of olanzapine in school-age children with schizophrenia. J Child Adolesc Psychopharmacol. 2003;13:301–9.

    Article  PubMed  Google Scholar 

  66. Martinez-Ortega JM, Funes-Godoy S, Diaz-Atienza F, Gutierrez-Rojas L, Perez-Costillas L, Gurpegui M. Weight gain and increase of body mass index among children and adolescents treated with antipsychotics: a critical review. Eur Child Adolesc Psychiatry. 2013;22(8):457–79. doi:10.1007/s00787-013-0399-5.

    Article  PubMed  Google Scholar 

  67. Meli M, Rauber-Lüthy C, Hoffmann-Walbeck P, Reinecke HJ, Prasa D, Stedtler U et al. Atypical antipsychotic poisoning in young children: a multicentre analysis of poisons centres data. Eur J Pediatrics. 2013:1–8. doi:10.1007/s00431-013-2241-y.

Download references

Acknowledgments

We would like to thank Thomasin Adams-Webber (Systems and Clinical Services Librarian, The Hospital for Sick Children) for her assistance with completion of the literature search.

Funding and Conflicts of Interest

No sources of funding were used to assist in the preparation of this study. Jacqueline Flank, Lillian Sung, Christopher Dvorak, Wendy Spettigue and L. Lee Dupuis have no conflicts of interest that are directly relevant to the content of this study.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Department of Pharmacy, Leslie Dan Faculty of Pharmacy, University of Toronto and The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Jacqueline Flank

  2. Division of Haematology/Oncology, Research Institute and Department of Pediatrics, The Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada

    Lillian Sung

  3. Division of Pediatric Allergy, Immunology and Bone Marrow Transplantation, University of California at San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA

    Christopher C. Dvorak

  4. Division of Psychiatry, Department of Pediatrics, Children’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada

    Wendy Spettigue

  5. Research Institute and Department of Pharmacy, The Hospital for Sick Children, Leslie Dan Faculty of Pharmacy, University of Toronto, 686 Bay Street, Toronto, ON, M5G 0A4, Canada

    L. Lee Dupuis

Authors
  1. Jacqueline Flank
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lillian Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher C. Dvorak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wendy Spettigue
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. Lee Dupuis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jacqueline Flank.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Flank, J., Sung, L., Dvorak, C.C. et al. The Safety of Olanzapine in Young Children: A Systematic Review and Meta-Analysis. Drug Saf 37, 791–804 (2014). https://doi.org/10.1007/s40264-014-0219-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40264-014-0219-y

Keywords

Search

Navigation