Skip to main content
Top
Published in: European Child & Adolescent Psychiatry 10/2018

01-10-2018 | Original Contribution

Assessing the risk of type 2 diabetes mellitus among children and adolescents with psychiatric disorders treated with atypical antipsychotics: a population-based nested case–control study

Authors: Hankil Lee, Dong-Ho Song, Jin-Won Kwon, Euna Han, Min-Jung Chang, Hye-Young Kang

Published in: European Child & Adolescent Psychiatry | Issue 10/2018

Login to get access

Abstract

To examine the associations between atypical antipsychotic (AAP) exposure and the development of type 2 diabetes mellitus (T2DM) in Korean pediatric patients with psychiatric disorders, we conducted a nested case–control study using the claims data of the National Health Insurance system of Korea between 2010 and 2014. A cohort of patients with psychiatric disorders was identified, and enrollment was taken as the date of the first psychiatric diagnosis. Cases involved patients with a diagnosis of T2DM or prescriptions for glucose lowering drugs after enrollment, and the identification of T2DM was defined as the index date. We performed a conditional logistic regression analysis for matched case–control data to assess associations between AAP exposure and T2DM, and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) are presented. From 1,092,019 patients aged 2–19 years, we identified 20,263 cases with T2DM and 80,043 controls, matched by sex, age, enrollment date, and primary psychiatric diagnosis. After adjusting for comorbidities, psychotropic medication history, and the healthcare institution characteristics, the aOR of having T2DM was significantly higher in multi-AAP users compared with non-users (aOR 1.89; 95% CI 1.63–2.20). Particularly high ORs for T2DM were observed in clozapine users compared with non-users (aOR 3.47; 95% CI 1.88–6.41). We observed a linear relationship between the increase in risperidone dose and the increase in the risk of developing T2DM. Our findings suggest a significantly increased risk of developing T2DM in child or adolescent patients with psychiatric disorders exposed to AAPs compared with those not exposed to AAPs.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lopez-Munoz F, Shen WW, Pae CU et al (2013) Trends in scientific literature on atypical antipsychotics in South Korea: a bibliometric study. Psychiatry Investig 10:8–16CrossRef Lopez-Munoz F, Shen WW, Pae CU et al (2013) Trends in scientific literature on atypical antipsychotics in South Korea: a bibliometric study. Psychiatry Investig 10:8–16CrossRef
2.
go back to reference Shen WW (1999) A history of antipsychotic drug development. Compr Psychiatry 40:407–414CrossRef Shen WW (1999) A history of antipsychotic drug development. Compr Psychiatry 40:407–414CrossRef
3.
go back to reference Datta SS, Kumar A, Wright SD, Furtado VA, Russell PS (2014) Evidence base for using atypical antipsychotics for psychosis in adolescents. Schizophr Bull 40:252–254CrossRef Datta SS, Kumar A, Wright SD, Furtado VA, Russell PS (2014) Evidence base for using atypical antipsychotics for psychosis in adolescents. Schizophr Bull 40:252–254CrossRef
4.
go back to reference Leucht S, Heres S, Kissling W, Davis JM (2011) Evidence-based pharmacotherapy of schizophrenia. Int J Neuropsychopharmacol 14:269–284CrossRef Leucht S, Heres S, Kissling W, Davis JM (2011) Evidence-based pharmacotherapy of schizophrenia. Int J Neuropsychopharmacol 14:269–284CrossRef
5.
go back to reference Correll CU, Kratochvil CJ, March JS (2011) Developments in pediatric psychopharmacology: focus on stimulants, antidepressants, and antipsychotics. J Clin Psychiatry 72:655–670CrossRef Correll CU, Kratochvil CJ, March JS (2011) Developments in pediatric psychopharmacology: focus on stimulants, antidepressants, and antipsychotics. J Clin Psychiatry 72:655–670CrossRef
6.
go back to reference Olfson M, Blanco C, Liu SM, Wang S, Correll CU (2012) National trends in the office-based treatment of children, adolescents, and adults with antipsychotics. Arch Gen Psychiatry 69:1247–1256CrossRef Olfson M, Blanco C, Liu SM, Wang S, Correll CU (2012) National trends in the office-based treatment of children, adolescents, and adults with antipsychotics. Arch Gen Psychiatry 69:1247–1256CrossRef
7.
go back to reference Zito JM, Safer DJ, Valluri S, Gardner JF, Korelitz JJ, Mattison DR (2007) Psychotherapeutic medication prevalence in Medicaid-insured preschoolers. J Child Adolesc Psychopharmacol 17:195–203CrossRef Zito JM, Safer DJ, Valluri S, Gardner JF, Korelitz JJ, Mattison DR (2007) Psychotherapeutic medication prevalence in Medicaid-insured preschoolers. J Child Adolesc Psychopharmacol 17:195–203CrossRef
8.
go back to reference Patel NC, Crismon ML, Hoagwood K et al (2005) Trends in the use of typical and atypical antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 44:548–556CrossRef Patel NC, Crismon ML, Hoagwood K et al (2005) Trends in the use of typical and atypical antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 44:548–556CrossRef
9.
go back to reference Galling B, Correll CU (2015) Do antipsychotics increase diabetes risk in children and adolescents? Expert Opin Drug Saf 14:219–241CrossRef Galling B, Correll CU (2015) Do antipsychotics increase diabetes risk in children and adolescents? Expert Opin Drug Saf 14:219–241CrossRef
10.
go back to reference Galling B, Roldan A, Nielsen RE et al (2016) Type 2 diabetes mellitus in youth exposed to antipsychotics: a systematic review and meta-analysis. JAMA Psychiatry 73:247–259CrossRef Galling B, Roldan A, Nielsen RE et al (2016) Type 2 diabetes mellitus in youth exposed to antipsychotics: a systematic review and meta-analysis. JAMA Psychiatry 73:247–259CrossRef
11.
go back to reference Correll CU (2008) Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. J Clin Psychiatry 69(Suppl 4):26–36PubMed Correll CU (2008) Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. J Clin Psychiatry 69(Suppl 4):26–36PubMed
12.
go back to reference Lambert BL, Cunningham FE, Miller DR, Dalack GW, Hur K (2006) Diabetes risk associated with use of olanzapine, quetiapine, and risperidone in veterans health administration patients with schizophrenia. Am J Epidemiol 164:672–681CrossRef Lambert BL, Cunningham FE, Miller DR, Dalack GW, Hur K (2006) Diabetes risk associated with use of olanzapine, quetiapine, and risperidone in veterans health administration patients with schizophrenia. Am J Epidemiol 164:672–681CrossRef
13.
go back to reference Rummel-Kluge C, Komossa K, Schwarz S et al (2010) Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res 123:225–233CrossRef Rummel-Kluge C, Komossa K, Schwarz S et al (2010) Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res 123:225–233CrossRef
14.
go back to reference Nielsen J, Skadhede S, Correll CU (2010) Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naive schizophrenia patients. Neuropsychopharmacology 35:1997–2004CrossRef Nielsen J, Skadhede S, Correll CU (2010) Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naive schizophrenia patients. Neuropsychopharmacology 35:1997–2004CrossRef
15.
go back to reference Fraguas D, Correll CU, Merchán-Naranjo J et al (2011) 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 21:621–645CrossRef Fraguas D, Correll CU, Merchán-Naranjo J et al (2011) 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 21:621–645CrossRef
16.
go back to reference Pringsheim T, Lam D, Ching H, Patten S (2011) Metabolic and neurological complications of second-generation antipsychotic use in children: a systematic review and meta-analysis of randomized controlled trials. Drug Saf 34:651–668CrossRef Pringsheim T, Lam D, Ching H, Patten S (2011) Metabolic and neurological complications of second-generation antipsychotic use in children: a systematic review and meta-analysis of randomized controlled trials. Drug Saf 34:651–668CrossRef
17.
go back to reference Sohn M, Talbert J, Blumenschein K, Moga DC (2015) Atypical antipsychotic initiation and the risk of type II diabetes in children and adolescents. Pharmacoepidemiol Drug Saf 24:583–591CrossRef Sohn M, Talbert J, Blumenschein K, Moga DC (2015) Atypical antipsychotic initiation and the risk of type II diabetes in children and adolescents. Pharmacoepidemiol Drug Saf 24:583–591CrossRef
18.
go back to reference Andrade SE, Lo JC, Roblin D et al (2011) Antipsychotic medication use among children and risk of diabetes mellitus. Pediatrics 128:1135–1141CrossRef Andrade SE, Lo JC, Roblin D et al (2011) Antipsychotic medication use among children and risk of diabetes mellitus. Pediatrics 128:1135–1141CrossRef
19.
go back to reference Pinhas-Hamiel O, Zeitler P (2007) Acute and chronic complications of type 2 diabetes mellitus in children and adolescents. Lancet 369:1823–1831CrossRef Pinhas-Hamiel O, Zeitler P (2007) Acute and chronic complications of type 2 diabetes mellitus in children and adolescents. Lancet 369:1823–1831CrossRef
20.
go back to reference Naughton MJ, Yi-Frazier JP, Morgan TM et al (2014) Longitudinal associations between sex, diabetes self-care, and health-related quality of life among youth with type 1 or type 2 diabetes mellitus. J Pediatr 164(1376–1383):e1371 Naughton MJ, Yi-Frazier JP, Morgan TM et al (2014) Longitudinal associations between sex, diabetes self-care, and health-related quality of life among youth with type 1 or type 2 diabetes mellitus. J Pediatr 164(1376–1383):e1371
21.
go back to reference Kessing LV, Thomsen AF, Mogensen UB, Andersen PK (2010) Treatment with antipsychotics and the risk of diabetes in clinical practice. Br J Psychiatry 197:266–271CrossRef Kessing LV, Thomsen AF, Mogensen UB, Andersen PK (2010) Treatment with antipsychotics and the risk of diabetes in clinical practice. Br J Psychiatry 197:266–271CrossRef
22.
go back to reference Nielsen RE, Laursen MF, Vernal DL et al (2014) Risk of diabetes in children and adolescents exposed to antipsychotics: a nationwide 12-year case–control study. J Am Acad Child Adolesc Psychiatry 53(971–979):e976 Nielsen RE, Laursen MF, Vernal DL et al (2014) Risk of diabetes in children and adolescents exposed to antipsychotics: a nationwide 12-year case–control study. J Am Acad Child Adolesc Psychiatry 53(971–979):e976
23.
go back to reference Bobo WV, Cooper WO, Stein CM et al (2013) Antipsychotics and the risk of type 2 diabetes mellitus in children and youth. JAMA Psychiatry 70:1067–1075CrossRef Bobo WV, Cooper WO, Stein CM et al (2013) Antipsychotics and the risk of type 2 diabetes mellitus in children and youth. JAMA Psychiatry 70:1067–1075CrossRef
24.
go back to reference Rubin DM, Kreider AR, Matone M et al (2015) Risk for incident diabetes mellitus following initiation of second-generation antipsychotics among Medicaid-enrolled youths. JAMA Pediatr 169:e150285CrossRef Rubin DM, Kreider AR, Matone M et al (2015) Risk for incident diabetes mellitus following initiation of second-generation antipsychotics among Medicaid-enrolled youths. JAMA Pediatr 169:e150285CrossRef
25.
go back to reference Liese AD, Lawson A, Song HR et al (2010) Evaluating geographic variation in type 1 and type 2 diabetes mellitus incidence in youth in four US regions. Health Place 16:547–556CrossRef Liese AD, Lawson A, Song HR et al (2010) Evaluating geographic variation in type 1 and type 2 diabetes mellitus incidence in youth in four US regions. Health Place 16:547–556CrossRef
26.
go back to reference Kim JH, Lee KS, Yoo KB, Park EC (2015) The differences in health care utilization between medical aid and health insurance: a longitudinal study using propensity score matching. PLoS One 10:e0119939CrossRef Kim JH, Lee KS, Yoo KB, Park EC (2015) The differences in health care utilization between medical aid and health insurance: a longitudinal study using propensity score matching. PLoS One 10:e0119939CrossRef
27.
go back to reference Legro RS, Arslanian SA, Ehrmann DA et al (2013) Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 98:4565–4592CrossRef Legro RS, Arslanian SA, Ehrmann DA et al (2013) Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 98:4565–4592CrossRef
28.
29.
go back to reference Etminan M (2004) Pharmacoepidemiology II: the nested case–control study—a novel approach in pharmacoepidemiologic research. Pharmacotherapy 24:1105–1109CrossRef Etminan M (2004) Pharmacoepidemiology II: the nested case–control study—a novel approach in pharmacoepidemiologic research. Pharmacotherapy 24:1105–1109CrossRef
30.
go back to reference Essebag V, Platt RW, Abrahamowicz M, Pilote L (2005) Comparison of nested case–control and survival analysis methodologies for analysis of time-dependent exposure. BMC Med Res Methodol 5:5CrossRef Essebag V, Platt RW, Abrahamowicz M, Pilote L (2005) Comparison of nested case–control and survival analysis methodologies for analysis of time-dependent exposure. BMC Med Res Methodol 5:5CrossRef
31.
go back to reference Gu XS, Rosenbaum PR (1993) Comparison of multivariate matching methods: structures, distances, and algorithms. J Comput Gr Stat 2:405–420 Gu XS, Rosenbaum PR (1993) Comparison of multivariate matching methods: structures, distances, and algorithms. J Comput Gr Stat 2:405–420
32.
go back to reference Saloner B, Matone M, Kreider AR et al (2014) Second-generation antipsychotic use among stimulant-using children, by organization of medicaid mental health. Psychiatr Serv 65:1458–1464CrossRef Saloner B, Matone M, Kreider AR et al (2014) Second-generation antipsychotic use among stimulant-using children, by organization of medicaid mental health. Psychiatr Serv 65:1458–1464CrossRef
33.
go back to reference Kumar A, Datta SS, Wright SD, Furtado VA, Russell PS (2013) Atypical antipsychotics for psychosis in adolescents. Cochrane Database Syst Rev 10:Cd009582 Kumar A, Datta SS, Wright SD, Furtado VA, Russell PS (2013) Atypical antipsychotics for psychosis in adolescents. Cochrane Database Syst Rev 10:Cd009582
34.
go back to reference Wang HR, Woo YS, Bahk WM (2013) Atypical antipsychotics in the treatment of delirium. Psychiatry Clin Neurosci 67:323–331CrossRef Wang HR, Woo YS, Bahk WM (2013) Atypical antipsychotics in the treatment of delirium. Psychiatry Clin Neurosci 67:323–331CrossRef
35.
go back to reference Crystal S, Olfson M, Huang C, Pincus H, Gerhard T (2009) Broadened use of atypical antipsychotics: safety, effectiveness, and policy challenges. Health Aff (Millwood) 28:w770–w781CrossRef Crystal S, Olfson M, Huang C, Pincus H, Gerhard T (2009) Broadened use of atypical antipsychotics: safety, effectiveness, and policy challenges. Health Aff (Millwood) 28:w770–w781CrossRef
36.
go back to reference Kwon JW, Park EJ, Jung SY, Sohn HS, Ryu H, Suh HS (2015) A large national cohort study of the association between bisphosphonates and osteonecrosis of the jaw in patients with osteoporosis: a nested case–control study. J Dent Res 94:212s–219sCrossRef Kwon JW, Park EJ, Jung SY, Sohn HS, Ryu H, Suh HS (2015) A large national cohort study of the association between bisphosphonates and osteonecrosis of the jaw in patients with osteoporosis: a nested case–control study. J Dent Res 94:212s–219sCrossRef
37.
go back to reference Bobes J, Arango C, Aranda P, Carmena R, Garcia-Garcia M, Rejas J (2007) Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: results of the CLAMORS Study. Schizophr Res 90:162–173CrossRef Bobes J, Arango C, Aranda P, Carmena R, Garcia-Garcia M, Rejas J (2007) Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: results of the CLAMORS Study. Schizophr Res 90:162–173CrossRef
38.
go back to reference Enger C, Jones ME, Kryzhanovskaya L, Doherty M, McAfee AT (2013) Risk of developing diabetes and dyslipidemia among adolescents with bipolar disorder or schizophrenia. Int J Adolesc Med Health 25:3–11CrossRef Enger C, Jones ME, Kryzhanovskaya L, Doherty M, McAfee AT (2013) Risk of developing diabetes and dyslipidemia among adolescents with bipolar disorder or schizophrenia. Int J Adolesc Med Health 25:3–11CrossRef
39.
go back to reference Montgomery M, Johnson P, Ewell P (2015) The Presence of risk factors for type 2 diabetes mellitus in underserved preschool children. Nurs Clin N Am 50:585–594CrossRef Montgomery M, Johnson P, Ewell P (2015) The Presence of risk factors for type 2 diabetes mellitus in underserved preschool children. Nurs Clin N Am 50:585–594CrossRef
40.
go back to reference World Health Organization (2016) WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index 2016 World Health Organization (2016) WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index 2016
41.
go back to reference Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, Sorensen HT, von Elm E, Langan SM (2015) The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. PLoS Med 12:e1001885CrossRef Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, Sorensen HT, von Elm E, Langan SM (2015) The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. PLoS Med 12:e1001885CrossRef
42.
go back to reference Newcomer JW (2005) Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 19(Suppl 1):1–93PubMed Newcomer JW (2005) Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 19(Suppl 1):1–93PubMed
43.
go back to reference Allison DB, Casey DE (2001) Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry 62(Suppl 7):22–31PubMed Allison DB, Casey DE (2001) Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry 62(Suppl 7):22–31PubMed
44.
go back to reference Graham KA, Perkins DO, Edwards LJ, Barrier RC Jr, Lieberman JA, Harp JB (2005) Effect of olanzapine on body composition and energy expenditure in adults with first-episode psychosis. Am J Psychiatry 162:118–123CrossRef Graham KA, Perkins DO, Edwards LJ, Barrier RC Jr, Lieberman JA, Harp JB (2005) Effect of olanzapine on body composition and energy expenditure in adults with first-episode psychosis. Am J Psychiatry 162:118–123CrossRef
45.
go back to reference Lean ME, Pajonk FG (2003) Patients on atypical antipsychotic drugs: another high-risk group for type 2 diabetes. Diabetes Care 26:1597–1605CrossRef Lean ME, Pajonk FG (2003) Patients on atypical antipsychotic drugs: another high-risk group for type 2 diabetes. Diabetes Care 26:1597–1605CrossRef
46.
go back to reference Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, Hu FB (2009) Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 301:2129–2140CrossRef Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, Hu FB (2009) Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 301:2129–2140CrossRef
47.
go back to reference Kim HY, Lee HW, Jung SH, Kang MH, Bae JN, Lee JS, Kim CE (2014) Prescription patterns for patients with schizophrenia in Korea: a focus on antipsychotic polypharmacy. Clin Psychopharmacol Neurosci 12:128–136CrossRef Kim HY, Lee HW, Jung SH, Kang MH, Bae JN, Lee JS, Kim CE (2014) Prescription patterns for patients with schizophrenia in Korea: a focus on antipsychotic polypharmacy. Clin Psychopharmacol Neurosci 12:128–136CrossRef
48.
go back to reference Newcomer JW, Nasrallah HA, Loebel AD (2004) The atypical antipsychotic therapy and metabolic issues national survey: practice patterns and knowledge of psychiatrists. J Clin Psychopharmacol 24:S1–S6CrossRef Newcomer JW, Nasrallah HA, Loebel AD (2004) The atypical antipsychotic therapy and metabolic issues national survey: practice patterns and knowledge of psychiatrists. J Clin Psychopharmacol 24:S1–S6CrossRef
49.
go back to reference Kang SH, Lee JI (2015) Metabolic disturbances independent of body mass in patients with schizophrenia taking atypical antipsychotics. Psychiatry Investig 12:242–248CrossRef Kang SH, Lee JI (2015) Metabolic disturbances independent of body mass in patients with schizophrenia taking atypical antipsychotics. Psychiatry Investig 12:242–248CrossRef
50.
go back to reference Baptista T, Kin NM, Beaulieu S, de Baptista EA (2002) Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry 35:205–219CrossRef Baptista T, Kin NM, Beaulieu S, de Baptista EA (2002) Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry 35:205–219CrossRef
51.
go back to reference Lee SYI (2011) Off-label or unlicensed drug prescriptions in child and adolescent psychiatry. J Korean Acad Child Adolesc Psychiatry 22:67–73CrossRef Lee SYI (2011) Off-label or unlicensed drug prescriptions in child and adolescent psychiatry. J Korean Acad Child Adolesc Psychiatry 22:67–73CrossRef
52.
go back to reference Mizuno Y, Suzuki T, Nakagawa A, Yoshida K, Mimura M, Fleischhacker WW, Uchida H (2014) Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr Bull 40:1385–1403CrossRef Mizuno Y, Suzuki T, Nakagawa A, Yoshida K, Mimura M, Fleischhacker WW, Uchida H (2014) Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr Bull 40:1385–1403CrossRef
Metadata
Title
Assessing the risk of type 2 diabetes mellitus among children and adolescents with psychiatric disorders treated with atypical antipsychotics: a population-based nested case–control study
Authors
Hankil Lee
Dong-Ho Song
Jin-Won Kwon
Euna Han
Min-Jung Chang
Hye-Young Kang
Publication date
01-10-2018
Publisher
Springer Berlin Heidelberg
Published in
European Child & Adolescent Psychiatry / Issue 10/2018
Print ISSN: 1018-8827
Electronic ISSN: 1435-165X
DOI
https://doi.org/10.1007/s00787-018-1123-2

Other articles of this Issue 10/2018

European Child & Adolescent Psychiatry 10/2018 Go to the issue