Antipsychotic-related weight gain and metabolic adverse effects have become a major focus, especially in youth.
Methods:
Review of randomized, cohort, and pharmacoepidemiologic studies of antipsychotic-related weight gain and metabolic adverse effects and of interventions for their reduction in youth.
Results:
Across 34 published head-to-head and placebo-controlled studies in youth with psychotic and bipolar disorders, weight gain ranged from 3.8 to 16.2 kg with olanzapine (n=353), 0.9–9.5 kg with clozapine (n=97), 1.9–7.2 kg with risperidone (n=571), 2.3–6.1 kg with quetiapine (n=133), and 0–4.4 kg with aripiprazole (n=451). In 24 placebo-controlled trials, the numbers-needed-to-harm for weight gain ≥7% in youth with bipolar disorder and schizophrenia were 39 (confidence interval [CI]: −1 to +6, not significant) for aripiprazole, 36 (CI: −1 to +7, not significant) for ziprasidone, 9 (CI: 7–14) for quetiapine, 6 (CI: 5–8) for risperidone, and 3 (CI: 3–4) for olanzapine. Data in youth with autism and disruptive behavior disorders, available only for some antipsychotics, suggest greater weight gain, possibly due to less prior antipsychotic exposure. Three-month results from a large cohort study in antipsychotic-naïve youth indicated that metabolic effects differ among second-generation antipsychotics, despite significant weight gain with all studied agents, suggesting additional, weight-independent effects. Further, pharmacoepidemiologic work indicates that antipsychotic polypharmacy increases the risk for obesity (odds ratio [OR]: 2.28 [CI: 1.49–3.65]) or any cardiovascular, cerebrovascular, or hypertensive adverse event (OR: 1.72 [CI: 1.10–2.69]). However, despite marked weight gain and its greater impact on youth, monitoring rates are low and studies of pharmacologic and behavioral interventions are extremely limited.
Conclusions:
More research is needed to develop strategies to minimize antipsychotic-related weight gain and metabolic effects in youth and to discover treatments with lower risk potential.
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References
1.
AllisonDB, MentoreJL, HeoM, ChandlerLP, CappelleriJC, InfanteMC, WeidenPJ. Antipsychotic-induced weight gain: A comprehensive research synthesis. Am J Psychiatry, 156:1686–1696. 1999.
2.
Alvarez-JimenezM, HetrickSE, Gonzalez-BlanchC, GleesonJF, McGorryPD. Non-pharmacological management of antipsychotic-induced weight gain: Systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry, 193:101–107. 2008.
3.
AmanM, ArnoldL, McDougleC, VitielloB, ScahillL, DaviesM. Acute and long-term safety and tolerability of risperidone in children with autism. J Child Adolesc Psychopharmacol, 15:869–884. 2005.
4.
AmanM, De SmedtG, DerivanA, LyonsB, FindlingR, RisperidoneD. Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence. Am J Psychiatry, 159:1337–1346. 2002.
5.
American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists and North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry, 65:267–272. 2004.
6.
ArangoC, RoblesO, ParelladaM, FraguasD, Ruiz-SanchoA, MedinaO, ZabalaA, BombinI, MorenoD. Olanzapine compared to quetiapine in adolescents with a first psychotic episode. Eur Child Adolesc Psychiatry, 18:418–428. 2009.
7.
ArmanS, SadramelyMR, NadiM, KoleiniN. A randomized, double-blind, placebo-controlled trial of metformin treatment for weight gain associated with initiation of risperidone in children and adolescents. Saudi Med J, 29:1130–1134. 2008.
8.
ArmenterosJ, LewisJ, DavalosM. Risperidone augmentation for treatment-resistant aggression in attention-deficit/hyperactivity disorder: A placebo-controlled pilot study. J Am Acad Child Adolesc Psychiatry, 46:558–565. 2007.
9.
BarnessLA, OpitzJM, Gilbert-BarnessE. Obesity: Genetic, molecular, environmental aspects. Am J Med Genet A, 143A:3016–3034. 2007.
10.
BuitelaarJ, van der GaagR, Cohen-KettenisP, MelmanC. A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities. J Clin Psychiatry, 62:239–248. 2001.
11.
CaliAM, CaprioS. Obesity in children and adolescents. J Clin Endocrinol Metab, 93:S31–S36. 2008.
12.
Castro-FornielesJ, ParelladaM, SoutulloCA, BaezaI, Gonzalez-PintoA, GraellM, PayaB, MorenoD, de la SernaE, ArangoC. Antipsychotic treatment in child and adolescent first-episode psychosis: A longitudinal naturalistic approach. J Child Adolesc Psychopharmacol, 18:327–336. 2008.
13.
ChangKD. The use of atypical antipsychotics in pediatric bipolar disorder. J Clin Psychiatry, 69,Suppl 4:4–8. 2008.
14.
ColtonCW, ManderscheidRW. Congruencies in increased mortality rates, years of potential life lost, causes of death among public mental health clients in eight states. Prev Chronic Dis, 3:A42. 2006.
15.
CorrellCU. Antipsychotic use in children and adolescents: Minimizing adverse effects to maximize outcomes. J Am Acad Child Adolesc Psychiatry, 47:9–20. 2008.
16.
CorrellCU. Multiple antipsychotic use associated with metabolic, cardiovascular adverse events in children, adolescents. Evid Based Ment Health, 12:93. 2009.
17.
CorrellCU, CarlsonHE. Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psychiatry, 45:771–791. 2006.
18.
CorrellCU, KratochvilCJ, MarchJ. Developments in pediatric psychopharmacology: focus on stimulants, antidepressants and antipsychotics. J Clin Psychiatry, 72:655–670. 2011a.
CorrellCU, LopsJD, FigenV, MalhotraAK, KaneJM, ManuP. QT interval duration and dispersion in children and adolescents treated with ziprasidone. J Clin Psychiatry, 72:854–860. 2011c.
21.
CorrellCU, ManuP, OlshanskiyV, NapolitanoB, KaneJM, MalhotraAK. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA, 302:1765–1773. 2009.
22.
CorrellCU, PenznerJB, ParikhUH, MughalT, JavedT, CarbonM, MalhotraAK. Recognizing and monitoring adverse events of second-generation antipsychotics in children and adolescents. Child Adolesc Psychiatr Clin N Am, 15:177–206. 2006.
23.
CorrellCU, SheridanEM, DelBelloMP. Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: A comparative analysis of acute, randomized, placebo-controlled trials. Bipolar Disord, 12:116–141. 2010.
24.
CorteseS, AngrimanM, MaffeisC, IsnardP, KonofalE, LecendreuxM, Purper-OuakilD, VincenziB, BernardinaBD, MourenMC. Attention-deficit/hyperactivity disorder (ADHD) and obesity: A systematic review of the literature. Crit Rev Food Sci Nutr, 48:524–537. 2008.
25.
DavisPH, DawsonJD, RileyWA, LauerRM. Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: The Muscatine Study. Circulation, 104:2815–2819. 2001.
26.
De HertM, DekkerJM, WoodD, KahlKG, HoltRI, MollerHJ. Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC)Eur Psychiatry, 24:412–424. 2009.
27.
De HertM, DetrauxJ, van WinkelR, CorrellCU. Antipsychotic medications: Metabolic, cardiovascular, cardiac risks. Nat Rev Endocrinol, 2011[Epub ahead of print].
28.
De HertM, DobbelaereM, SheridanEM, CohenD, CorrellCU. 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, 26:144–158. 2011.
29.
DelBelloM, FindlingR, EarleyW, AcevedoL, StankowskiJ. Efficacy of quetiapine in children, adolescents with bipolar mania: A 3-week, double-blind, randomized, placebo-controlled trial. Presented at 46th Annual Meeting of the American College of Neuropsychopharmacology, Boca Raton, FL, 2007a.
30.
DelBelloM, FindlingR, WangP, GrundapaneniB, VersavelM. Efficacy, safety of ziprasidone in pediatric bipolar disorder. Presented at 63rd Annual Meeting of the Society of Biological Psychiatry, Washington, DC, 2008a.
31.
DelBelloMP, AdlerCM, WhitselRM, StanfordKE, StrakowskiSM. A 12-week single-blind trial of quetiapine for the treatment of mood symptoms in adolescents at high risk for developing bipolar I disorder. J Clin Psychiatry, 68:789–795. 2007b.
32.
DelBelloMP, ChangK, WelgeJA, AdlerCM, RanaM, HoweM, BryanH, VogelD, SampangS, DelgadoSV, SorterM, StrakowskiSM. A double-blind, placebo-controlled pilot study of quetiapine for depressed adolescents with bipolar disorder. Bipolar Disord, 11:483–493. 2009.
33.
DelBelloMP, VersavelM, IceK, KellerD, MiceliJ. Tolerability of oral ziprasidone in children and adolescents with bipolar mania, schizophrenia, or schizoaffective disorder. J Child Adolesc Psychopharmacol, 18:491–499. 2008b.
34.
EltermanRD, GlauserTA, WyllieE, ReifeR, WuSC, PledgerG. A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. Topiramate YP Study Group. Neurology, 52:1338–1344. 1999.
35.
FindlingR, CavusI, PappadolulosE, BackinskyM, SchwartzJ, VanderburgD. A placebo-controlled trial to evaluate the efficacy, safety of flexibly dosed oral ziprasidone in adolescent subjects with schizophrenia. Schizophr Res, 117:437. 2010a.
36.
FindlingR, KlineK, MckennaK, EarleyW, StankowskiJ, PathakS. Efficacy, safety of quetiapine in adolescents with schizophrenia: A 6-week, double-blind, randomized, placebo-controlled trial. Presented at 55th Annual Meeting of the American Academy of Child and Adolescent Psychiatry, Chicago, IL, 2008a.
37.
FindlingR, NyilasM, ForbesR, McQuadeR, JinN, IwamotoT. Acute treatment of pediatric bipolar I disorder, manic or mixed episode, with aripiprazole: A randomized, double-blind, placebo-controlled study. J Clin Psychiatry, 70:1441–1451. 2009.
38.
FindlingR, RobbA, NyilasM, ForbesR, JinN, IvanovaS. A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. Am J Psychiatry, 165:1432–1441. 2008b.
39.
FindlingRL, JohnsonJL, McClellanJ, FrazierJA, VitielloB, HamerRM, LiebermanJA, RitzL, McNamaraNK, LinglerJ, HlastalaS, PiersonL, PugliaM, MaloneyAE, KaufmanEM, NoyesN, SikichL. Double-blind maintenance safety and effectiveness findings from the treatment of early-onset schizophrenia spectrum (TEOSS) study. J Am Acad Child Adolesc Psychiatry, 49:583–594. 2010b.
40.
FindlingRL, KlineK, MckennaK, EarleyWR, StankowskiJ, PathakS. Efficacy, safety of quetiapine in adolescents with schizophrenia: A 6-week, double-blind, randomized, placebo-controlled trial. Presented at 55th Annual Meeting of the American Academy of Child and Adolescent Psychiatry, Chicago, IL, 2008c.
41.
FindlingRL, McNamaraNK, BranickyLA, SchluchterMD, LemonE, BlumerJL. A double-blind pilot study of risperidone in the treatment of conduct disorder. J Am Acad Child Adolesc Psychiatry, 39:509–516. 2000.
42.
FleischhakerC, HeiserP, HennighausenK, Herpertz-DahlmannB, HoltkampK, Mehler-WexC, RauhR, RemschmidtH, SchulzE, WarnkeA. Weight gain associated with clozapine, olanzapine and risperidone in children and adolescents. J Neural Transm, 114:273–280. 2007.
43.
FleischhakerC, HeiserP, HennighausenK, Herpertz-DahlmannB, HoltkampK, Mehler-WexC, RauhR, RemschmidtH, SchulzE, WarnkeA. Weight gain in children and adolescents during 45 weeks treatment with clozapine, olanzapine and risperidone. J Neural Transm, 115:1599–1608. 2008.
44.
Food and Drug Administration. Pediatric indications. www.fda.gov/…/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM164423.pdf20092010January.
45.
FraguasD, CorrellCU, Merchan-NaranjoJ, Rapado-CastroM, ParelladaM, MorenoC, ArangoC. 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, 21:621–645. 2011.
46.
FraguasD, Merchan-NaranjoJ, LaitaP, ParelladaM, MorenoD, Ruiz-SanchoA, CifuentesA, GiraldezM, ArangoC. Metabolic and hormonal side effects in children and adolescents treated with second-generation antipsychotics. J Clin Psychiatry, 69:1166–1175. 2008.
47.
Freeman-FobbsP. Feeding our children to death: The tragedy of childhood obesity in America. J Natl Med Assoc, 95:119. 2003.
HaasM, DelbelloMP, PandinaG, KushnerS, Van HoveI, AugustynsI, QuirozJ, KusumakarV. Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: A randomized, double-blind, placebo-controlled study. Bipolar Disord, 11:687–700. 2009a.
50.
HaasM, EerdekensM, KushnerS, SingerJ, AugustynsI, QuirozJ, PandinaG, KusumakarV. Efficacy, safety and tolerability of two dosing regimens in adolescent schizophrenia: Double-blind study. Br J Psychiatry, 194:158–164. 2009b.
51.
HaasM, UnisAS, ArmenterosJ, CopenhaverMD, QuirozJA, KushnerSF. A 6-week, randomized, double-blind, placebo-controlled study of the efficacy and safety of risperidone in adolescents with schizophrenia. J Child Adolesc Psychopharmacol, 19:611–621. 2009c.
52.
HellingsJA, ZarconeJR, CrandallK, WallaceD, SchroederSR. Weight gain in a controlled study of risperidone in children, adolescents and adults with mental retardation and autism. J Child Adolesc Psychopharmacol, 11:229–238. 2001.
53.
HollanderE, WassermanS, SwansonE, ChaplinW, SchapiroM, ZagurskyK. A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder. J Child Adolescent Psychopharmacology, 16:541–548. 2006.
54.
HuangES, BasuA, O'GradyM, CaprettaJC. Projecting the future diabetes population size and related costs for the U.S.Diabetes Care, 32:2225–2229. 2009.
55.
JensenJB, KumraS, LeittenW, OberstarJ, AnjumA, WhiteT, WozniakJ, LeeSS, SchulzSC. A comparative pilot study of second-generation antipsychotics in children and adolescents with schizophrenia-spectrum disorders. J Child Adolesc Psychopharmacol, 18:317–326. 2008.
56.
JensenPS, YoungstromEA, SteinerH, FindlingRL, MeyerRE, MaloneRP, CarlsonGA, CoccaroEF, AmanMG, BlairJ, DoughertyD, FerrisC, FlynnL, GreenE, HoagwoodK, HutchinsonJ, LaughrenT, LeveLD, NovinsDK, VitielloB. Consensus report on impulsive aggression as a symptom across diagnostic categories in child psychiatry: Implications for medication studies. J Am Acad Child Adolesc Psychiatry, 46:309–322. 2007.
57.
JerrellJM. Adverse events associated with psychotropic treatment in African American children and adolescents. J Natl Med Assoc, 102:375–383. 2010.
58.
JerrellJM, McIntyreRS. Adverse events in children and adolescents treated with antipsychotic medications. Hum Psychopharmacol, 23:283–290. 2008.
59.
KahnRS, FleischhackerWW, BoterH, DavidsonM, VergouweY, KeetIP, GheorgheMD, RybakowskiJK, GalderisiS, LibigerJ, HummerM, DollfusS, Lopez-IborJJ, HranovLG, GaebelW, PeuskensJ, LindeforsN, Riecher-RosslerA, GrobbeeDE. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: An open randomised clinical trial. Lancet, 371:1085–1097. 2008.
60.
KaneJM, CorrellCU. Past and present progress in the pharmacologic treatment of schizophrenia. J Clin Psychiatry, 71:1115–1124. 2010.
61.
KimSF, HuangAS, SnowmanAM, TeuscherC, SnyderSH. From the cover: Antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase. Proc Natl Acad Sci U S A, 104:3456–3459. 2007.
62.
KleinDJ, CottinghamEM, SorterM, BartonBA, MorrisonJA. A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. Am J Psychiatry, 163:2072–2079. 2006.
63.
KroezeWK, HufeisenSJ, PopadakBA, RenockSM, SteinbergS, ErnsbergerP, JayathilakeK, MeltzerHY, RothBL. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology, 28:519–526. 2003.
64.
KryzhanovskayaLA, Robertson-PlouchCK, XuW, CarlsonJL, MeridaKM, DittmannRW. The safety of olanzapine in adolescents with schizophrenia or bipolar I disorder: A pooled analysis of 4 clinical trials. J Clin Psychiatry, 70:247–258. 2009a.
65.
KryzhanovskayaL, SchulzSC, McDougleC, FrazierJ, DittmannR, Robertson-PlouchC, BauerT, XuW, WangW, CarlsonJ, TohenM. Olanzapine versus placebo in adolescents with schizophrenia: A 6-week, randomized, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry, 48:60–70. 2009b.
KumraS, KranzlerH, Gerbino-RosenG, KesterH, De ThomasC, KafantarisV, CorrellC, KaneJ. Clozapine and “high-dose” olanzapine in refractory early-onset schizophrenia: A 12-week randomized and double-blind comparison. Biol Psychiatry, 63:524–529. 2008a.
68.
KumraS, OberstarJV, SikichL, FindlingRL, McClellanJM, VinogradovS, Charles SchulzS. Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia. Schizophr Bull, 34:60–71. 2008b.
69.
LewisD, WinnerP, SaperJ, NessS, PolverejanE, WangS, KurlandCL, NyeJ, YuenE, EerdekensM, FordL. Randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of topiramate for migraine prevention in pediatric subjects 12 to 17 years of age. Pediatrics, 123:924–934. 2009.
70.
LiS, ChenW, SrinivasanSR, BondMG, TangR, UrbinaEM, BerensonGS. Childhood cardiovascular risk factors and carotid vascular changes in adulthood: The Bogalusa Heart Study. JAMA, 290:2271–2276. 2003.
71.
LiebermanJA, StroupTS, McEvoyJP, SwartzMS, RosenheckRA, PerkinsDO, KeefeRS, DavisSM, DavisCE, LebowitzBD, SevereJ, HsiaoJK. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med, 353:1209–1223. 2005.
72.
LubyJ, MrakotskyC, StaletsM, BeldenA, HeffelfingerA, WilliamsM. Risperidone in preschool children with autistic spectrum disorders: An investigation of safety and efficacy. J Child Adolesc Psychopharmacol, 16:575–587. 2006.
MaayanL, HoogendoornC, SweatV, ConvitA. Disinhibited eating in obese adolescents is associated with orbitofrontal volume reductions and executive dysfunction. Obesity (Silver Spring), 19:1382–1387. 2011.
75.
MaayanL, VakhrushevaJ, CorrellCU. Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: A systematic review and meta-analysis. Neuropsychopharmacology, 35:1520–1530. 2010a.
76.
MaayanL, VakhrushevaJ, SheridanEM, CorrellCU. Efficacy, tolerability of risperidone across the age span: A meta-analytic comparison of placebo controlled trials. Presented at New Clinical Drug Evaluation Unit 50th Anniversary Meeting, Boca Raton, FL, 2010b.
77.
MarcusRN, OwenR, KamenL, ManosG, McQuadeRD, CarsonWH, AmanMG. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry, 48:1110–1119. 2009.
78.
McDougleCJ, StiglerKA, EricksonCA, PoseyDJ. Atypical antipsychotics in children and adolescents with autistic and other pervasive developmental disorders. J Clin Psychiatry, 69,Suppl 4:15–20. 2008.
79.
McIntyreRS, JerrellJM. Metabolic and cardiovascular adverse events associated with antipsychotic treatment in children and adolescents. Arch Pediatr Adolesc Med, 162:929–935. 2008.
80.
MolnarD. The prevalence of the metabolic syndrome and type 2 diabetes mellitus in children and adolescents. Int J Obes Relat Metab Disord, 28,Suppl 3:S70–S74. 2004.
81.
MorratoEH, CuffelB, NewcomerJW, LombardoI, KamatS, BarronJ. Metabolic risk status and second-generation antipsychotic drug selection: A retrospective study of commercially insured patients. J Clin Psychopharmacol, 29:26–32. 2009.
82.
MorratoEH, DrussB, HartungDM, ValuckRJ, AllenR, CampagnaE, NewcomerJW. Metabolic testing rates in 3 state Medicaid programs after FDA warnings and ADA/APA recommendations for second-generation antipsychotic drugs. Arch Gen Psychiatry, 67:17–24. 2010a.
83.
MorratoEH, NicolGE, MaahsD, DrussBG, HartungDM, ValuckRJ, CampagnaE, NewcomerJW. Metabolic screening in children receiving antipsychotic drug treatment. Arch Pediatr Adolesc Med, 164:344–351. 2010b.
84.
NagarajR, SinghiP, MalhiP. Risperidone in children with autism: Randomized, placebo-controlled, double-blind study. J Child Neurol, 21:450–455. 2006.
85.
NarulaPK, RehanHS, UnniKE, GuptaN. Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: A double-blind, placebo-controlled trial. Schizophr Res, 118:218–223. 2010.
86.
NathanBM, MoranA. Metabolic complications of obesity in childhood and adolescence: More than just diabetes. Curr Opin Endocrinol Diabetes Obes, 15:21–29. 2008.
87.
National Institute of Mental Health. Reducing weight gain and improving metabolic function in children being treated with antipsychotics. ClinicalTrials.gov[Internet]Bethesda, MD: National Library of Medicine (US), 2000[cited December 1, 2009] Available from: http://clinicaltrials.gov/show/NCT00806234NLM Identifier: NCT00806234.
88.
National Institutes of Health and Washington University School of Medicine. Metabolic Effects of Antipsychotics in Children (MEAC)ClinicalTrials.gov[Internet]Bethesda, MD: National Library of Medicine (US), 2000[cited December 1, 2009]http://clinicaltrials.gov/show/NCT00205699NLM Identifier: NCT00205699.
89.
NewcomerJW. Second-generation (atypical) antipsychotics and metabolic effects: A comprehensive literature review. CNS Drugs, 19,Suppl 1:1–93. 2005.
90.
NielsenJ, SkadhedeS, CorrellCU. Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naive schizophrenia patients. Neuropsychopharmacology, 35:1997–2004. 2010.
91.
OgdenCL, CarrollMD, CurtinLR, LambMM, FlegalKM. Prevalence of high body mass index in US children and adolescents, 2007–2008. JAMA, 303:242–249. 2010.
92.
OlfsonM, BlancoC, LiuL, MorenoC, LajeG. National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. Arch Gen Psychiatry, 63:679–685. 2006.
93.
OlfsonM, CrystalS, HuangC, GerhardT. Trends in antipsychotic drug use by very young, privately insured children. J Am Acad Child Adolesc Psychiatry, 49:13–23. 2010.
94.
OsbyU, CorreiaN, BrandtL, EkbomA, SparenP. Time trends in schizophrenia mortality in Stockholm county, Sweden: Cohort study. BMJ, 321:483–484. 2000.
95.
OwenR, SikichL, MarcusRN, Corey-LisleP, ManosG, McQuadeRD, CarsonWH, FindlingRL. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics, 124:1533–1540. 2009.
96.
Pinhas-HamielO, DolanLM, DanielsSR, StandifordD, KhouryPR, ZeitlerP. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr, 128:608–615. 1996.
97.
RosenbloomAL. Fetal and childhood nutrition in type 2 diabetes in children and adults. Pediatr Diabetes, 1:34–39discussion 39–402000.
98.
SaferDJ. A comparison of risperidone-induced weight gain across the age span. J Clin Psychopharmacol, 24:429–436. 2004.
99.
SalleeFR, KurlanR, GoetzCG, SingerH, ScahillL, LawG, DittmanVM, ChappellPB. Ziprasidone treatment of children and adolescents with Tourette's syndrome: A pilot study. J Am Acad Child Adolesc Psychiatry, 39:292–299. 2000.
100.
ScahillL, LeckmanJF, SchultzRT, KatsovichL, PetersonBS. A placebo-controlled trial of risperidone in Tourette syndrome. Neurology, 60:1130–1135. 2003.
SheaS, TurgayA, CarrollA, SchulzM, OrlikH, SmithI, DunbarF. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics, 114:e634–e641. 2004.
103.
SikichL, FrazierJA, McClellanJ, FindlingRL, VitielloB, RitzL, AmblerD, PugliaM, MaloneyAE, MichaelE, De JongS, SlifkaK, NoyesN, HlastalaS, PiersonL, McNamaraNK, Delporto-BedoyaD, AndersonR, HamerRM, LiebermanJA. 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, 165:1420–1431. 2008.
104.
SikichL, HamerRM, BashfordRA, SheitmanBB, LiebermanJA. A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: A double-blind, randomized, 8-week trial. Neuropsychopharmacology, 29:133–145. 2004.
105.
SnyderR, TurgayA, AmanM, BinderC, FismanS, CarrollA. Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs. J Am Acad Child Adolesc Psychiatry, 41:1026–1036. 2002.
106.
SwadiHS, CraigBJ, PirwaniNZ, BlackVC, BuchanJC, BobierCM. A trial of quetiapine compared with risperidone in the treatment of first onset psychosis among 15- to 18-year-old adolescents. Int Clin Psychopharmacol, 25:1–6. 2010.
107.
TarriconeI, Ferrari GozziB, SerrettiA, GriecoD, BerardiD. Weight gain in antipsychotic-naive patients: A review and meta-analysis. Psychol Med, 40:187–200. 2010.
108.
TohenM, KryzhanovskayaL, CarlsonG, DelbelloM, WozniakJ, KowatchR, WagnerK, FindlingR, LinD, Robertson-PlouchC, XuW, DittmannR, BiedermanJ. Olanzapine versus placebo in the treatment of adolescents with bipolar mania. Am J Psychiatry, 164:1547–1556. 2007.
109.
TramontinaS, ZeniC, KetzerC, PheulaG, NarvaezJ, RohdeL. Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: A pilot randomized clinical trial. J Clin Psychiatry, 70:756–764. 2009.
110.
UrbinaEM, KimballTR, McCoyCE, KhouryPR, DanielsSR, DolanLM. Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function. Circulation, 119:2913–2919. 2009.
111.
Van BellinghenM, De TrochC. Risperidone in the treatment of behavioral disturbances in children and adolescents with borderline intellectual functioning: A double-blind, placebo-controlled pilot trial. J Child Adolesc Psychopharmacol, 11:5–13. 2001.
112.
ViewegWV, KuhnleyLJ, KuhnleyEJ, AnumEA, SoodB, PandurangiA, SilvermanJJ. Body mass index (BMI) in newly admitted child and adolescent psychiatric inpatients. Prog Neuropsychopharmacol Biol Psychiatry, 29:511–515. 2005.
113.
WeissR, DziuraJ, BurgertTS, TamborlaneWV, TaksaliSE, YeckelCW, AllenK, LopesM, SavoyeM, MorrisonJ, SherwinRS, CaprioS. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med, 350:2362–2374. 2004.
114.
WozniakJ, MickE, WaxmonskyJ, KotarskiM, HantsooL, BiedermanJ. 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, 19:539–545. 2009.
115.
YauPL, JavierDC, RyanCM, TsuiWH, ArdekaniBA, TenS, ConvitA. Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus. Diabetologia, 53:2298–2306. 2010.
