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.
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.
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.
No studies were identified with a primary focus on evaluating safety, and the adverse effects reported in the included studies were heterogeneous.
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, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
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.
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].
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.
Masi G. Pharmacotherapy of pervasive developmental disorders in children and adolescents. CNS Drugs. 2004;18(14):1031–52.
Eli Lilly and Company. Zyprexa prescribing information. Indianapolis: Eli Lilly and Co.; 2010.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Sholevar EH, Baron DA, Hardie TL. Treatment of childhood-onset schizophrenia with olanzapine. J Child Adolesc Psychopharmacol. 2000;10(2):69–78.
Sethi S, Setiya R, Lallar K. Successful treatment of Sydenham chorea with olanzapine. J Pediatric Neurol. 2006;4(3):171–4.
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.
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.
Bengi Semerci Z. Olanzapine in Tourette’s disorder. J Am Acad Child Adolesc Psychiatry. 2000;39(2):140.
Bozkurt H, Mukaddes NM. Catatonia in a child with autistic disorder. Turk J Pediatr. 2010;52(4):435–8.
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.
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.
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.
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.
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.
Courvoisie HE, Cooke DW, Riddle MA. Olanzapine-induced diabetes in a seven-year-old boy. J Child Adolesc Psychopharmacol. 2004;14(4):612–6.
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.
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.
Nguyen M, Murphy T. Olanzapine and hypertriglyceridemia. J Am Acad Child Adolesc Psychiatry. 2001;40(2):133.
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.
Chang KD, Ketter TA. Mood stabilizer augmentation with olanzapine in acutely manic children. J Child Adolesc Psychopharmacol. 2000;10(1):45–9.
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.
Malek-Ahmadi P, Simonds JF. Olanzapine for autistic disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry. 1998;37(9):902.
Krishnamoorthy J, King BH. Open-label olanzapine treatment in five preadolescent children. J Child Adolesc Psychopharmacol. 1998;8(2):107–13.
Horrigan JP, Barnhill LJ, Courvoisie HE. Olanzapine in PDD. J Am Acad Child Adolesc Psychiatry. 1997;36(9):1166–7.
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.
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.
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.
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.
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.
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.
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.
Bonin MM, Burkhart KK. Olanzapine overdose in a 1-year-old male. Pediatr Emerg Care. 1999;15(4):266–7.
Bond GR, Thompson JD. Olanzapine pediatric overdose. Ann Emerg Med. 1999;34(2):292–3.
Yip L, Dart RC, Graham K. Olanzapine toxicity in a toddler. Pediatrics. 1998;102(6):1494.
Chambers RA, Caracansi A, Weiss G. Olanzapine overdose cause of acute extrapyramidal symptoms. Am J Psychiatry. 1998;155(11):1630–1.
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.
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.
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.
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.
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.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
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
- Tardive Dyskinesia
- Neuroleptic Malignant Syndrome
- Paediatric Cancer Patient
- Atypical Antipsychotic Agent