European Neuropsychopharmacology
Volume 19, Issue 9 , Pages 629-635 , September 2009

Antipsychotics in children and adolescents: Increasing use, evidence for efficacy and safety concerns

  • Benedetto Vitiello

      Affiliations

    • National Institute of Mental Health, USA
    • Corresponding Author InformationCorresponding author. NIMH, Room 7147, 6001 Executive Blvd., Bethesda, MD 20892-9633, USA.
    • ,
  • Christoph Correll

      Affiliations

    • The Zucker Hillside Hospital, Glen Oaks, NY, USA
    • ,
  • Barbara van Zwieten-Boot

      Affiliations

    • Medicines Evaluation Board, Den Haag, The Netherlands
    • ,
  • Alessandro Zuddas

      Affiliations

    • University of Cagliari, Dept. of Neuroscience, Cagliari, Italy
    • ,
  • Mara Parellada

      Affiliations

    • Department of Psychiatry, Hospital General Universitario Gregorio Marañón and Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
    • ,
  • Celso Arango

      Affiliations

    • Department of Psychiatry, Hospital General Universitario Gregorio Marañón and Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain

Received 8 January 2009 ,Revised 22 April 2009 ,Accepted 28 April 2009.

References 

  1. Aman MG, Hollway JA, McDougle CJ, Scahill L, Tierney E, McCracken JT, et al. Cognitive effects of risperidone in children with autism and irritable behavior. J. Child Adolesc. Psychopharmacol. 2008;18:227–236
  2. Aman MG, Arnold LE, McDougle CJ, Vitiello B, Scahill L, Davies M, et al. Acute and long-term safety and tolerability of risperidone in children with autism. J. Child Adolesc. Psychopharmacol. 2005;15:869–884
  3. Aman MG, De Smedt G, Derivan A, Lyons B, Findling RL, Risperidone Disruptive Behavior Study Group . Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence. Am. J. Psychiatry. 2002;159:1337–1346
  4. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity, 2004. Consensus development conference on antipsychotic drugs and obesity and diabetes. Obes. Res. 12, 362–368.
  5. Anderson GM, Scahill L, McCracken JT, McDougle CJ, Aman MG, Tierney E, et al. Effects of short- and long-term risperidone treatment on prolactin levels in children with autism. Biol. Psychiatry. 2007;61:545–550
  6. Aparasu RR, Bhatara V. Patterns and determinants of antipsychotic prescribing in children and adolescents, 2003–2004. Curr. Med. Res. Opin. 2007;23:49–56
  7. Arango C, Parellada M, Moreno DM. Clinical effectiveness of new generation antipsychotics in adolescent patients. Eur. Neuropsychopharmacol. 2004;14(Suppl. 4):S471–S479
  8. Arango, C., Robles, O., Parellada, M., Fraguas, D., Ruiz-Sancho, A., Medina, O., Zabala, A., Bombín, I., Moreno, D., 2009. Olanzapine compared to quetiapine in adolescents with a first psychotic episode. Eur. Child Adolesc. Psychiatry 18, 418–428.
  9. Bobes J, Arango C, Aranda P, Carmena R, Garcia-Garcia M, Rejas J CLAMORS Study Collaborative Group. Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: results of the CLAMORS Study. Schizophr. Res. 2007;90:162–173
  10. Buitelaar JK, van der Gaag RJ, Cohen-Kettenis P, Melman CT. A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities. J. Clin. Psychiatry. 2001;62:239–248
  11. Case BG, Olfson M, Marcus SC, Siegel C. Trends in the inpatient mental health treatment of children and adolescents in US community hospitals between 1990 and 2000. Arch. Gen. Psychiatry. 2007;64:89–96
  12. Castro-Fornieles J, Parellada M, Soutullo CA, Baeza I, Gonzalez-Pinto A, Graell M, et al. Antipsychotic treatment in child and adolescent first-episode psychosis: a longitudinal naturalistic approach. J. Child Adolesc. Psychopharmacol. 2008;18:327–336
  13. Cavazzoni P, Mukhopadhyay N, Carlson C, Breier A, Buse J. Retrospective analysis of risk factors in patients with treatment-emergent diabetes during clinical trials of antipsychotic medications. Br. J. Psychiatry. 2004;47:S94–101
  14. Chang KD. The use of atypical antipsychotics in pediatric bipolar disorder. J. Clin. Psychiatry. 2008;69(Suppl. 4):4–8
  15. Cooper WO, Hickson GB, Fuchs DC, Arbogast PG, Ray WA. New users of antipsychotic medications among children enrolled in TennCare. Arch. Ped. Adolesc. Med. 2004;158:829–830
  16. Correll CU. Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. J. Clin. Psychiatry. 2008;69(Suppl. 4):26–36
  17. Correll CU. Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes. J. Am. Acad. Child Adolesc. Psychiatry. 2008;47:9–20
  18. Correll CU, Malhotra AK. Pharmacogenetics of antipsychotic-induced weight gain. Psychopharmacology (Berl.). 2004;174:477–489
  19. Correll CU, Carlson HE. Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J. Am. Acad. Child. Adolesc. Psychiatry. 2006;45:771–791
  20. Correll CU, Penzner JB, Parikh UH, Mughal T, Javed T, Carbon M, et al. Recognizing and monitoring adverse events of second-generation antipsychotics in children and adolescents. Child Adolesc. Psychiatr. Clin. N. Am. 2006;15:177–206
  21. de Castro MJ, Fraguas D, Laita P, Moreno D, Parellada M, Pascual D, et al. QTc changes after 6 months of second-generation antipsychotic treatment in children and adolescents. J. Child Adolesc. Psychopharmacol. 2008;18:381–383
  22. Dittmann RW, Meyer E, Freisleder FJ, Remschmidt H, Mehler-Wex C, Junghanss J, et al. Effectiveness and tolerability of olanzapine in the treatment of adolescents with schizophrenia and related psychotic disorders: results from a large, prospective, open-label study. J. Child Adolesc. Psychopharmacol. 2008;18:54–69
  23. Domino ME, Swartz MS. Who are the new users of antipsychotic medications?. Psychiatr. Serv. 2008;59:507–514
  24. Elias M. New antipsychotic drugs carry risks for children. In: USAToday May 2. 2006;
  25. Findling RL, Kusumakar V, Daneman D, Moshang T, Desmedt G, Binder C. Prolactin levels during long-term risperidone treatment in children and adolescents. J. Clin. Psychiatry. 2003;64:1362–1369
  26. Findling RL, Steiner H, Weller EB. Use of antipsychotics in children and adolescents. J. Clin. Psychiatry. 2005;66(Suppl 7):29–40
  27. Findling RL, Robb A, Nyilas M, Forbes RA, Jin N, Ivanova S, et al. A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. Am. J. Psychiatry. 2008;165:1432–1441
  28. Fraguas D, Merchán-Naranjo J, Laita P, Parellada M, Moreno D, Ruiz-Sancho A, et al. Metabolic and hormonal side effects in children and adolescents treated with second-generation antipsychotics. J. Clin. Psychiatry. 2008;69:1166–1175
  29. Gencer O, Emiroglu FN, Miral S, Baykara B, Baykara A, Dirik E. Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder. An open label maintenance study. Eur. Child Adolesc. Psychiatry. 2008;17:217–225
  30. Guo JJ, Keck PE, Corey-Lisle PK, Li H, Jiang D, Jang R, et al. Risk of diabetes mellitus associated with atypical antipsychotic use among patients with bipolar disorder: a retrospective, population-based, case–control study. J. Clin. Psychiatry. 2006;67:1055–1061
  31. Haas M, Karcher K, Pandina GJ. Treating disruptive behavior disorders with risperidone: a 1-year, open-label safety study in children and adolescents. J. Child Adolesc. Psychopharmacol. 2008;18:337–345
  32. Harris G. Use of Antipsychotics in Children is Criticized. New York Times; 2008;November 18
  33. Haupt DW. Differential metabolic effects of antipsychotic treatments. Eur. Neuropsychopharmacol. 2006;16:S149–155
  34. Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS). Arch. Gen. Psychiatry. 2006;63:1079–1087
  35. Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomized clinical trial. Lancet. 2008;371:1085–1097
  36. Kalverdijk JJ, Tobi H, van den Berg PB, Buiskool J, Wagenaar L, Minderaa RB, et al. Use of antipsychotic drugs among Dutch youths between 1997 and 2005. Psychiatr. Serv. 2008;59:554–560
  37. Kim SF, Huang AS, Snowman AM, Teuscher C, Snyder SH. Antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase. PNAS. 2007;104:3456–3459
  38. Klein DJ, Cottingham EM, Sorter M, Barton BA, Morrison JA. 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. 2006;163:2071–2079
  39. Kryzhanovskaya L, Schultz SC, McDougle C, Frazier J, Dittman R, Robertson-Plouch C, et al. Olanzapine versus placebo in adolescents with schizophrenia: a 6-week, randomized, double-blind, placebo-controlled trial. J. Am. Acad. Child Adolesc. Psychiatry. 2009;48:60–70
  40. Kumra S, Oberstar JV, Sikich L, Findling RL, McClellan JM, Vinogradov S, et al. Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia. Schizophr. Bull. 2008;34:60–71
  41. Kumra S, Kranzler H, Gerbino-Rosen G, Kester HM, DeThomas C, Kafantaris V, et al. Clozapine and “high-dose” olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison. Biol. Psychiatry. 2008;63:524–529
  42. Laita P, Cifuentes A, Doll A, Llorente C, Cortés I, Parellada M, et al. Antipsychotic-related abnormal involuntary movements and metabolic and endocrine side effects in children and adolescents. J. Child Adolesc. Psychopharmacol. 2007;17:487–502
  43. Leucht S, Corves C, Arbter D, Engel RR, Chunbo L, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2008;[published online]
  44. Leucht S, Barnes TR, Kissling W, Engel RR, Correll C, Kane JM. Relapse prevention in schizophrenia with new-generation antipsychotics: a systematic review and exploratory meta-analysis of randomized, controlled trials. Am. J. Psychiatry. 2003;160:1209–1222
  45. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 2005;353:1209–1223
  46. Miral S, Gencer O, Inal-Emiroglu FN, Baykara B, Baykara A, Dirik E. Risperidone versus haloperidol in children and adolescents with AD: a randomized, controlled, double-blind trial. Eur. Child Adolesc. Psychiatry. 2008;17:1–8
  47. Moran-Gates T, Gan L, Park YS, Zhang K, Baldessarini RJ, Tarazi FI. Repeated antipsychotic drug exposure in developing rats: dopamine receptor effects. Synapse. 2006;59:92–100
  48. Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch. Gen. Psychiatry. 2007;64:1032–1039
  49. Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, et al. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch. Gen. Psychiatry. 2002;59:337–345
  50. Olfson M, Blanco C, Liu L, Moreno C, Laje G. National trends in the outpatient treatment of children and adolescents with antipsychotics. Arch. Gen. Psychiatry. 2006;63:679–685
  51. Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence?. Nat. Rev. Neurosci. 2008;9:947–957
  52. Rani F, Murray ML, Byrne PJ, Wong ICK. Epidemiologic features of antipsychotic prescribing to children and adolescents in primary care in the United Kingdom. Pediatrics. 2008;121:1002–1009
  53. Research Units on Pediatric Psychopharmacology Autism Network . Risperidone in children with autism and serious behavioral problems. N. Engl. J. Med. 2002;347:314–321
  54. Research Units on Pediatric Psychopharmacology Autism Network . Risperidone treatment of autistic disorder: longer-term benefits and blinded discontinuation after 6 months. Am. J. Psychiatry. 2005;162:1361–1369
  55. Reyes M, Olah R, Csaba K, Augustyns I, Eerdekens M. Long-term safety and efficacy of risperidone in children with disruptive behaviour disorders. Results of a 2-year extension study. Eur. Child Adolesc. Psychiatry. 2006;15:97–104
  56. Reyes M, Buitelaar J, Toren P, Augustyns I, Eerdekens M. A randomized, double-blind, placebo-controlled study of risperidone maintenance treatment in children and adolescents with disruptive behavior disorders. Am. J. Psychiatry. 2006;163:402–410
  57. Schooler N, Rabinowitz J, Davidson M, Emsley R, Harvey PD, Kopala L, et al. Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. Am. J. Psychiatry. 2005;162:947–953
  58. 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;63:721–730
  59. Sikich L. Efficacy of atypical antipsychotics in early-onset schizophrenia and other psychotic disorders. J. Clin. Psychiatry. 2008;69(Suppl.4):21–25
  60. Sikich L, Hamer RM, Bashford RA, Sheitman BB, Lieberman JA. A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial. Neuropsychopharmacol. 2004;29:133–145
  61. Sikich L, Frazier JA, McClellan J, Findling RL, Vitiello B, Ritz L, et al. Double-blind comparison of antipsychotics in early onset schizophrenia and schizoaffective disorder. Am. J. Psychiatry. 2008;165:1420–1431
  62. Snyder R, Turgay A, Aman M, Binder C, Fisman S, Carroll A Risperidone Conduct Study Group. Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs. J. Am. Acad. Child. Adolesc. Psychiatry. 2002;41:1026–1036
  63. Staller J. The effect of long-term antipsychotic treatment on prolactin. J. Child Adolesc. Psychopharmacol. 2006;16:317–326
  64. Tohen M, Kryzhanovskaya L, Carlson G, DelBello M, Wozniak J, Kowatch R, et al. Olanzapine versus placebo in the treatment of adolescents with bipolar mania. Am. J. Psychiatry. 2007;164:1547–1556
  65. Troost PW, Lahuis BE, Steenhuis MP, Ketelaars CE, Buitelaar JK, van Engeland H, et al. Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study. J. Am. Acad. Child Adolesc. Psychiatry. 2005;44:1137–1144
  66. Tyrer P, Kendall T. The spurious advance of antipsychotic drug therapy. Lancet. 2008;373:4–5
  67. Vitiello B, Riddle MA, Greenhill LL, March JS, Levine J, Schachar R, et al. How can we improve the assessment of safety in child and adolescent psychopharmacology?. J. Am. Acad. Child Adolesc. Psychiatry. 2003;42:634–641
  68. Zito JM, Safer DJ, de Jong-van den Berg LTW, Janhsen K, Fgert JM, Gardner JF, et al. A three-country comparison of psychotropic medication prevalence in youth. Child Adolesc. Psychiatry Ment. Health. 2008;2:26

PII: S0924-977X(09)00121-7

doi: 10.1016/j.euroneuro.2009.04.008

European Neuropsychopharmacology
Volume 19, Issue 9 , Pages 629-635 , September 2009

Article Tools