Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Drug Safety
Published in: Drug Safety 10/2014

01-10-2014 | Systematic Review

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

Authors: Jacqueline Flank, Lillian Sung, Christopher C. Dvorak, Wendy Spettigue, L. Lee Dupuis

Published in: Drug Safety | Issue 10/2014

Login to get access

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.
Appendix
Available only for authorised users
Literature
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.PubMedCrossRef
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
3.
4.
Masi G. Pharmacotherapy of pervasive developmental disorders in children and adolescents. CNS Drugs. 2004;18(14):1031–52.PubMedCrossRef
5.
Eli Lilly and Company. Zyprexa prescribing information. Indianapolis: Eli Lilly and Co.; 2010.
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.PubMedCrossRef
7.
8.
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.CrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.CrossRef
13.
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.PubMedCrossRef
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.PubMedCrossRef
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.CrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
20.
21.
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
32.
Sholevar EH, Baron DA, Hardie TL. Treatment of childhood-onset schizophrenia with olanzapine. J Child Adolesc Psychopharmacol. 2000;10(2):69–78.PubMedCrossRef
33.
Sethi S, Setiya R, Lallar K. Successful treatment of Sydenham chorea with olanzapine. J Pediatric Neurol. 2006;4(3):171–4.
34.
35.
36.
Bengi Semerci Z. Olanzapine in Tourette’s disorder. J Am Acad Child Adolesc Psychiatry. 2000;39(2):140.PubMedCrossRef
37.
Bozkurt H, Mukaddes NM. Catatonia in a child with autistic disorder. Turk J Pediatr. 2010;52(4):435–8.PubMed
38.
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.PubMedCrossRef
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.PubMedCrossRef
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​.CrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
46.
Nguyen M, Murphy T. Olanzapine and hypertriglyceridemia. J Am Acad Child Adolesc Psychiatry. 2001;40(2):133.PubMedCrossRef
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.PubMedCrossRef
48.
Chang KD, Ketter TA. Mood stabilizer augmentation with olanzapine in acutely manic children. J Child Adolesc Psychopharmacol. 2000;10(1):45–9.PubMedCrossRef
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.PubMedCrossRef
50.
Malek-Ahmadi P, Simonds JF. Olanzapine for autistic disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry. 1998;37(9):902.PubMedCrossRef
51.
Krishnamoorthy J, King BH. Open-label olanzapine treatment in five preadolescent children. J Child Adolesc Psychopharmacol. 1998;8(2):107–13.PubMedCrossRef
52.
Horrigan JP, Barnhill LJ, Courvoisie HE. Olanzapine in PDD. J Am Acad Child Adolesc Psychiatry. 1997;36(9):1166–7.PubMedCrossRef
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.PubMedCrossRefPubMedCentral
54.
55.
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.CrossRef
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.PubMedCrossRef
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.PubMedCrossRef
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.PubMedCrossRef
60.
Bonin MM, Burkhart KK. Olanzapine overdose in a 1-year-old male. Pediatr Emerg Care. 1999;15(4):266–7.PubMedCrossRef
61.
62.
63.
Chambers RA, Caracansi A, Weiss G. Olanzapine overdose cause of acute extrapyramidal symptoms. Am J Psychiatry. 1998;155(11):1630–1.PubMed
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
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.PubMedCrossRef
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.PubMedCrossRef
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.
Metadata
Title
The Safety of Olanzapine in Young Children: A Systematic Review and Meta-Analysis
Authors
Jacqueline Flank
Lillian Sung
Christopher C. Dvorak
Wendy Spettigue
L. Lee Dupuis
Publication date
01-10-2014
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 10/2014
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.1007/s40264-014-0219-y

Other articles of this Issue 10/2014

Drug Safety 10/2014 Go to the issue

Special Article

Teaching Pharmacovigilance: the WHO-ISoP Core Elements of a Comprehensive Modular Curriculum

Leading Article

Text Mining for Adverse Drug Events: the Promise, Challenges, and State of the Art

Leading Article

Restrictive Reimbursement Policies: Bias Implications for Claims-Based Drug Safety Studies

Abstracts

INTERNATIONAL SOCIETY OF PHARMACOVIGILANCE

Original Research Article

Comparison of Pregnancy and Lactation Labeling for Attention-Deficit Hyperactivity Disorder Drugs Marketed in Australia, the USA, Denmark, and the UK

Leading Article

Pharmacovigilance in China: Current Situation, Successes and Challenges