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CNS Drugs

, Volume 20, Issue 10, pp 841–866 | Cite as

Children with Schizophrenia

Clinical Picture and Pharmacological Treatment
  • Gabriele Mast
  • Maria Mucci
  • Cinzia Pari
Review Article

Abstract

Awareness of childhood-onset schizophrenia is rapidly increasing, with a more precise definition now available of the clinical picture and early signs, the outcome and the treatment strategies. Premorbid developmental impairments, including language, motor and social deficits, are more frequent and more pronounced in earlier-than in later-onset forms of schizophrenia. This ‘pandysmaturation’ is reported from the first months of life in more than half of the children who will develop childhood-onset schizophrenia, and it suggests a more severe and early disruption of brain development compared with the adolescent- and adult-onset disorder. The insidious onset in at least 75% of children, the high rates of premorbid problems and the hesitancy on the part of clinicians to make a diagnosis of schizophrenia in a child usually delay the recognition of the syndrome. Elementary auditory hallucinations are the most frequent positive symptom, while visual and tactile hallucinations are rarer. Delusions are less complex than in adolescents and are usually related to childhood themes. Negative symptoms are largely predominant, namely flat or inappropriate affect. A marked deterioration from the previous level of functioning is present in all these children, and an impaired outcome is reported in approximately 50–60% of them.

The main diagnostic challenges are with differentiating childhood-onset schizophrenia from affective disorders (both depression and bipolar disorder) with psychotic symptoms, pervasive developmental disorders and severe personality disorders. Post-traumatic stress disorder and obsessive-compulsive disorder without insight may also be misdiagnosed as schizophrenia. Furthermore, approximately 10% of children from the community report nonpsychotic hallucinations or delusions. Finally, children with atypical psychotic features that do not strictly fit diagnostic criteria for schizophrenia have been described, and new labels have been proposed to categorise these clinical patterns, such as multidimensionally impaired disorder and multiple complex developmental disorder.

In the context of a multimodal approach, including behavioral, social, scholastic and familial interventions, a pharmacological treatment is usually the core treatment. Available experience from the few controlled studies, open studies and case reports on pharmacotherapy in children with schizophrenia aged <12 years is critically analysed in this review, with particular reference to the use of atypical antipsychotics in clinical practice. To date, the major evidence supports the efficacy of risperidone and olanzapine, while clozapine seems an effective option in treatment-refractory cases. Published experience with newer atypical antipsychotics (quetiapine, ziprasidone, aripiprazole) is still lacking in this age range. Safety data (namely extrapyramidal symptoms, weight gain, hyperprolactinaemia, haematological adverse effects, seizures, hepatotoxicity, metabolic effects, neuroleptic malignant syndrome and cardiovascular effects) are reviewed and discussed, along with strategies for management.

Keywords

Schizophrenia Clozapine Risperidone Olanzapine Negative Symptom 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Dr Masi is a consultant for Eli Lilly, has received research grants from Eli Lilly and has been a speaker for Eli Lilly, GlaxoSmithKline, Janssen Cilag and Pfizer. Drs Mucci and Pari have no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to assist in the preparation of this review.

References

  1. 1.
    Kraepelin E. Dementia praecox and paraphrenia (Barclay RM, translator). 8th ed. Edinburgh: S Livingstone, 1919Google Scholar
  2. 2.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 2nd ed. Washington, DC: American Psychiatric Association, 1968Google Scholar
  3. 3.
    Kolvin I. Studies in childhood psychoses: I. Diagnostic criteria and classification. Br J Psychiatry 1971 Apr; 118(545): 381–4Google Scholar
  4. 4.
    Werry JS. Child and adolescent (early onset) schizophrenia: a review in light of DSM-III-R. J Autism Dev Disord 1992 Dec; 22(4): 601–24PubMedCrossRefGoogle Scholar
  5. 5.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
  6. 6.
    McKenna K, Gordon CT, Lenane M, et al. Looking for childhood-onset schizophrenia: the first 71 cases screened. J Am Acad Child Adolesc Psychiatry 1994 Jun; 33(5): 636–44PubMedCrossRefGoogle Scholar
  7. 7.
    Green WH, Padron-Gayol M, Hardesty A, et al. Schizophrenia with childhood onset: a phenomenological study of 38 cases. J Am Acad Child Adolesc Psychiatry 1992 Sep; 31(5): 968–76PubMedCrossRefGoogle Scholar
  8. 8.
    Russell AT, Bott L, Sammons C. The phenomenology of schizophrenia occurring in childhood. J Am Acad Child Adolesc Psychiatry 1989 May; 28(3): 399–407PubMedCrossRefGoogle Scholar
  9. 9.
    Russell AT. The clinical presentation of childhood onset schizophrenia. Schizophr Bull 1994; 20(4): 631–46PubMedCrossRefGoogle Scholar
  10. 10.
    Spencer EK, Campbell M. Children with schizophrenia: diagnosis, phenomenology and pharmacotherapy. Schizophr Bull 1994; 20(4): 713–25PubMedCrossRefGoogle Scholar
  11. 11.
    Asarnow JR, Tompson MC, Goldstein MJ. Childhood-onset schizophrenia: a follow-up study. Schizophr Bull 1994; 20(4): 599–617PubMedCrossRefGoogle Scholar
  12. 12.
    Maziade M, Bouchard SD, Gingras N, et al. Long-term stability of diagnosis and symptoms dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence: I. Nosology, sex and age at onset. Br J Psychiatry 1996 Sep; 169(3): 361–70Google Scholar
  13. 13.
    Jacobsen LK, Rapoport JL. Childhood-onset schizophrenia: implication of clinical and neurobiological research. J Child Psychol Psychiatry 1998 Jan; 39(1): 101–3PubMedCrossRefGoogle Scholar
  14. 14.
    Nicolson R, Rapoport JL. Childhood onset schizophrenia: rare but worth studying. Biol Psychiatry 1999 Nov; 46(10): 1418–28PubMedCrossRefGoogle Scholar
  15. 15.
    McClellan J, McCurry C, Snell J, et al. Early onset psychotic disorders: course and outcome over a two years period. J Am Acad Child Adolesc Psychiatry 1999 Nov; 38(11): 1380–9PubMedCrossRefGoogle Scholar
  16. 16.
    Hollis C. Adult outcomes of child- and adolescent-onset schizophrenia: diagnostic stability and predictive validity. Am J Psychiatry 2000 Oct; 157(10): 1652–9PubMedCrossRefGoogle Scholar
  17. 17.
    Helgeland MI, Torgersen S. Stability and prediction of schizophrenia from adolescent to adulthood. Eur Child Adolesc Psychiatry 2005 Mar; 14(2): 83–94PubMedCrossRefGoogle Scholar
  18. 18.
    Asarnow JR. Childhood-onset schizotypal disorder: a follow-up study and comparison with childhood-onset schizophrenia. J Child Adolesc Psychopharmacol 2005 Jun; 15(3): 395–402PubMedCrossRefGoogle Scholar
  19. 19.
    Asarnow JR, Ben-Meir S. Children with schizophrenia spectrum and depressive disorders: a comparative study of premorbid adjustment, onset pattern and severity of impairment. J Child Psychol Psychiatry 1988 Jul; 29(4): 477–88PubMedCrossRefGoogle Scholar
  20. 20.
    Alaghband-Rad J, McKenna K, Gordon CT, et al. Childhood onset schizophrenia: the severity of premorbid course. J Am Acad Child Adolesc Psychiatry 1995 Oct; 34(10): 1273–83PubMedCrossRefGoogle Scholar
  21. 21.
    Hollis C. Child and adolescent (juvenile onset) schizophrenia: a case control study of premorbid developmental impairments. Br J Psychiatry 1995 Apr; 166(4): 489–95PubMedCrossRefGoogle Scholar
  22. 22.
    Nicolson R, Lenane M, Singaracharlu S, et al. Premorbid speech and language impairments in childhood-onset schizophrenia: association with risk factors. Am J Psychiatry 2000 May; 157(5): 794–800PubMedCrossRefGoogle Scholar
  23. 23.
    McClellan J, Breiger D, McCurry C, et al. Premorbid functioning in early-onset psychotic disorders. J Am Acad Child Adolesc Psychiatry 2003 Jun; 42(6): 666–72PubMedCrossRefGoogle Scholar
  24. 24.
    Fish B, Kendler KS. Abnormal infant neurodevelopment predicts schizophrenia spectrum disorders. J Child Adolesc Psychopharmacol 2005 Jun; 15(3): 348–61PubMedCrossRefGoogle Scholar
  25. 25.
    Watkins J, Asarnow R, Tanguay P. Symptom development in childhood onset schizophrenia. J Child Psychol Psychiatry 1988 Nov; 29(6): 865–78PubMedCrossRefGoogle Scholar
  26. 26.
    Werry JS, McClellan JM, Chard L. Early onset schizophrenia, bipolar and schizoaffective disorders: a clinical follow up study. J Am Acad Child Adolesc Psychiatry 1991 May; 30(3): 457–65PubMedCrossRefGoogle Scholar
  27. 27.
    McClellan J, Werry JS, Ham M. A follow up study of early onset psychosis: comparison between outcome diagnoses of schizophrenia, mood disorders and personality disorders. J Autism Dev Disord 1993 Jun; 23(2): 243–62PubMedCrossRefGoogle Scholar
  28. 28.
    Volkmar F, Cohen DJ. Comorbid association of autism and schizophrenia. Am J Psychiatry 1991 Dec; 148(12): 1705–7PubMedGoogle Scholar
  29. 29.
    Mouridsen SE, Rich B, Isager T. Psychiatric morbidity in disintegrative psychosis and infantile autism: a long-term follow-up study. Psychopathology 1999 Jul–Aug; 32(4): 177–83PubMedCrossRefGoogle Scholar
  30. 30.
    Sporn AL, Addington AM, Gogtay N, et al. Pervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness? Biol Psychiatry 2004 May; 55(10): 989–94PubMedCrossRefGoogle Scholar
  31. 31.
    Nicolson R, Brookner FB, Lenane M, et al. Parental schizophrenia spectrum disorders in childhood-onset and adult-onset schizophrenia. Am J Psychiatry 2003 Mar; 160(3): 490–5PubMedCrossRefGoogle Scholar
  32. 32.
    Werry JS, McClellan JM. Predicting outcome in child and adolescent (early onset) schizophrenia and bipolar disorder. J Am Acad Child Adolesc Psychiatry 1992 Jan; 31(1): 147–50PubMedCrossRefGoogle Scholar
  33. 33.
    Schaeffer JL, Ross RL. Childhood-onset schizophrenia: premorbid and prodromal: diagnostic and treatment histories. J Am Acad Child Adolesc Psychiatry 2002 May; 41(5): 538–45PubMedCrossRefGoogle Scholar
  34. 34.
    Hollis C. Schizophrenia and allied disorders. In: Rutter M, Taylor E, editors. Child and adolescent psychiatry. 4th ed. Maiden (MA): Blackwell Publishing, 2002: 612–35Google Scholar
  35. 35.
    McClellan J, McCurry C, Speltz ML, et al. Symptom factors in early-onset psychotic disorders. J Am Acad Child Adolesc Psychiatry 2002 Jul; 41(7): 791–8PubMedCrossRefGoogle Scholar
  36. 36.
    Caplan R. Communication deficits in childhood schizophrenia spectrum disorders. Schizophr Bull 1994; 20(4): 671–83PubMedCrossRefGoogle Scholar
  37. 37.
    Asarnow JR, Tompson MC, McGrath E. Annotation: childhood onset schizophrenia: clinical and treatment issues. J Child Psychol Psychiatry 2004 Feb; 45(2): 180–94PubMedCrossRefGoogle Scholar
  38. 38.
    Calderoni D, Wudarsky M, Bhangoo R, et al. Differentiating childhood onset schizophrenia from psychotic mood disorders. J Am Acad Child Adolesc Psychiatry 2001 Oct; 40(10): 1190–6PubMedCrossRefGoogle Scholar
  39. 39.
    Eggers C. Schizoaffective disorders in childhood: a follow-up study. J Autism Dev Disord 1989 Jun; 19(2): 327–42PubMedCrossRefGoogle Scholar
  40. 40.
    Lay B, Blanz B, Hartmann M, et al. The psychosocial outcome of adolescent-onset schizophrenia: a 12-year followup. Schizophr Bull 2001; 27(2): 801–16Google Scholar
  41. 41.
    Eggers C, Bunk D. The long-term course of childhood-onset schizophrenia: a 42-year follow-up. Schizophr Bull 1997 Apr; 23(1): 105–17PubMedCrossRefGoogle Scholar
  42. 42.
    McClellan J, McCurry C. Early onset psychotic disorders: diagnostic stability and clinical characteristics. Eur Child Adolesc Psychiatry 1999; 8Suppl. 1: 113–9Google Scholar
  43. 43.
    Maziade M, Bouchard SD, Gingras N, et al. Long-term stability of diagnosis and symptoms dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence: II. Positive/negative distinction and childhood predictors of adult outcome. Br J Psychiatry 1996 Sep; 169(3): 371–8Google Scholar
  44. 44.
    McGee R, Williams S, Poulton R. Hallucinations in nonpsychotic children. J Am Acad Child Adolesc Psychiatry 2000 Jan; 39(1): 12–3PubMedCrossRefGoogle Scholar
  45. 45.
    Del Beccaro M, Burke MB, McCauley E. Hallucinations in children: a follow-up study. J Am Acad Child Adolesc Psychiatry 1988 Jul; 27(4): 462–5PubMedCrossRefGoogle Scholar
  46. 46.
    Chambers WJ, Puig-Antich J, Tabrizi MA, et al. Psychotic symptoms in prepubertal major depressive disorder. Arch Gen Psychiatry 1982 Aug; 39(8): 921–7PubMedCrossRefGoogle Scholar
  47. 47.
    Ulloa RE, Birmaher B, Axelson D, et al. Psychosis in a pediatric mood and anxiety disorders clinic: phenomenology and clinical correlates. J Am Acad Child Adolesc Psychiatry 2000 Mar; 39(3): 337–45PubMedCrossRefGoogle Scholar
  48. 48.
    Geller B, Fox LW, Clark KA. Rate and predictors of prepubertal bipolarity during follow-up of 6- to 12 year-old depressed children. J Am Acad Child Adolesc Psychiatry 1994 May; 33(4): 461–8PubMedCrossRefGoogle Scholar
  49. 49.
    Faraone SV, Biederman J, Wozniak J, et al. Is comorbidity with ADHD a marker for juvenile-onset mania? J Am Acad Child Adolesc Psychiatry 1997 Aug; 36(8): 1046–55PubMedCrossRefGoogle Scholar
  50. 50.
    Masi G, Perugi G, Toni C, et al. Attention deficit hyperactivity disorder: bipolar comorbidity in children and adolescents. Bipolar Disord 2006; 8(4): 373–81PubMedCrossRefGoogle Scholar
  51. 51.
    Masi G, Akiskal HS, Akiskal K. Detecting the risk for affective spectrum disorders in children of bipolar parents. In: Maj M, Lopez-Ibor JJ, Sartorius N, et al., editors. Early detection and management of mental disorders. New York: Wiley, 2004: 163–84Google Scholar
  52. 52.
    Famularo R, Fenton T, Kinscherff R, et al. Psychiatric comorbidity in childhood post-traumatic stress disorder. Child Abuse Negl 1996 Oct; 20(10): 953–61PubMedCrossRefGoogle Scholar
  53. 53.
    Donnelly CL. Pharmacologic treatment approaches for children and adolescents with posttraumatic stress disorder. Child Adolesc Psychiatr Clin N Am 2003 Apr; 12(2): 251–69PubMedCrossRefGoogle Scholar
  54. 54.
    Wolff S. Schizoid personality in childhood and adult life: III. The childhood picture. Br J Psychiatry 1991 Nov; 159: 629–35Google Scholar
  55. 55.
    Ad-Dab’Bagh Y, Greenfield B. Multiple complex developmental disorder: the “multiple and complex” evolution of the “childhood borderline syndrome” construct. J Am Acad Child Adolesc Psychiatry 2001 Aug; 40(8): 954–64PubMedCrossRefGoogle Scholar
  56. 56.
    Lofgren DP, Bemporad J, King J, et al. A prospective follow-up study of so-called borderline children. Am J Psychiatry 1991 Nov; 148(11): 1541–7PubMedGoogle Scholar
  57. 57.
    Masi G, Millepiedi S, Mucci M, et al. A naturalistic study of referred children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 2005 Jul; 44(7): 673–81PubMedCrossRefGoogle Scholar
  58. 58.
    Kumra S, Jacobsen LK, Lenane M, et al. Multidimensionally impaired disorder: is it a variant of very early onset schizophrenia? J Am Acad Child Adolesc Psychiatry 1998 Jan; 37(1): 91–9PubMedCrossRefGoogle Scholar
  59. 59.
    Towbin KE, Dykens EM, Pearson GS, et al. Conceptualizing “borderline syndrome of childhood” and “childhood schizophrenia” as a developmental disorder. J Am Acad Child Adolesc Psychiatry 1993 Jul; 32(4): 775–82PubMedCrossRefGoogle Scholar
  60. 60.
    Nicolson R, Lenane M, Brookner F, et al. Children and adolescents with psychotic disorder not otherwise specified: a 2- to 8- year follow-up study. Compr Psychiatry 2001 Jul–Aug; 42(4): 319–25PubMedCrossRefGoogle Scholar
  61. 61.
    Stayer C, Sporn A, Gogtay N, et al. Multidiniensionally impaired: the good news. J Child Adolesc Psychopharmacol 2005 Jun; 15(3): 510–9PubMedCrossRefGoogle Scholar
  62. 62.
    Cohen DJ, Paul R, Volkmar F. Issues in the classification of pervasive developmental disorders and associate conditions. In: Cohen DJ, Donnellan AM, editors. Handbook of autism and developmental disorders. New York: Wiley, 1997: 20–39Google Scholar
  63. 63.
    Buitelaar JK, Van der Gaag RJ. Diagnostic rules for children with PDD-NOS and multiple complex developmental disorder. J Child Psychol Psychiatry 1998 Sep; 39(6): 911–9PubMedCrossRefGoogle Scholar
  64. 64.
    Van der Gaag RJ, Caplan R, Engeland H, et al. A controlled study of formal thought disorder in children with autism and multiple complex developmental disorder. J Child Adolesc Psychopharmacol 2005 Jun; 15(3): 465–76PubMedCrossRefGoogle Scholar
  65. 65.
    Van der Gaag RJ, Buitelaar J, Van den Ban E, et al. A controlled multivariate chart review of multiple complex developmental disorder. J Am Acad Child Adolesc Psychiatry 1995 Aug; 34(8): 1096–106PubMedCrossRefGoogle Scholar
  66. 66.
    Spencer EK, Kafantaris V, Padron-Gayol MV, et al. Haloperidol in schizophrenic children: early findings from a study in progress. Psychopharmacol Bull 1992; 28(2): 183–6PubMedGoogle Scholar
  67. 67.
    Kumra S, Jacobsen LK, Lenane M, et al. Childhood-onset schizophrenia: an open label study of olanzapine in adolescents. J Am Acad Child Adolesc Psychiatry 1998 Apr; 37(4): 377–85PubMedCrossRefGoogle Scholar
  68. 68.
    Sikich L, Hamer RM, Bashford RA, et al. A pilot study of risperidone, olanzapine and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial. Neuropsychopharmacology 2004 Jan; 29(1): 133–45PubMedCrossRefGoogle Scholar
  69. 69.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. revised. Washington, DC: American Psychiatric Association, 1987Google Scholar
  70. 70.
    Spencer EK, Campbell M. Children with schizophrenia: diagnosis, phenomenology and pharmacotherapy. Schizophr Bull 1994; 20(4): 713–25PubMedCrossRefGoogle Scholar
  71. 71.
    Campbell M, Rapoport JL, Simpson GM. Antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 1999 May; 38(5): 537–45PubMedCrossRefGoogle Scholar
  72. 72.
    Brenner HD, Dencker SJ, Goldstein MJ, et al. Defining treatment refractoriness in schizophrenia. Schizophr Bull 1990; 16(4): 551–61PubMedCrossRefGoogle Scholar
  73. 73.
    Kumra S, Jacobsen LK, Lenane M, et al. Case series: spectrum of neuroleptic-induced movement disorders and extrapyramidal side effects in childhood-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 1998 Feb; 37(2): 221–7PubMedCrossRefGoogle Scholar
  74. 74.
    Kumra S, Frazier JA, Jacobsen LK, et al. Childhood onset schizophrenia: a double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry 1996 Dec; 53(12): 1090–7PubMedCrossRefGoogle Scholar
  75. 75.
    Towbin KE, Dykens EM, Pugliese RG. Clozapine for early developmental delays with childhood-onset schizophrenia: protocol and 15-month outcome. J Am Acad Child Adolesc Psychiatry 1994 Jun; 33(5): 651–7PubMedCrossRefGoogle Scholar
  76. 76.
    Mozes T, Toren P, Chernauzan N, et al. Clozapine treatment in very early onset schizophrenia. J Am Acad Child Adolesc Psychiatry 1994 Jan; 33(1): 65–70PubMedCrossRefGoogle Scholar
  77. 77.
    Kowatch RA, Suppes T, Gilfillan SK, et al. Clozapine treatment of children and adolescents with bipolar disorder and schizophrenia: a clinical case series. J Child Adolesc Psychopharmacol 1995; 5: 241–53CrossRefGoogle Scholar
  78. 78.
    MacEwan TH, Morton MJ. Use of clozapine in a child with treatment-resistant schizophrenia. Br J Psychiatry 1996 Mar; 168(3): 376–8PubMedCrossRefGoogle Scholar
  79. 79.
    Turetz M, Mozes T, Toren P, et al. An open trial of clozapine in neuroleptic-resistant childhood-onset schizophrenia. Br J Psychiatry 1997 Jun; 170: 507–10PubMedCrossRefGoogle Scholar
  80. 80.
    Gogtay N, Sporn A, Alfaro CL, et al. Clozapine-induced akathisia in children with schizophrenia. J Child Adolesc Psychopharmacol 2002 Winter; 12(4): 347–9PubMedCrossRefGoogle Scholar
  81. 81.
    Sporn A, Gogtay N, Ortiz-Aguayo R, et al. Clozapine-induced neutropenia in children: management with lithium carbonate. J Child Adolesc Psychopharmacol 2003 Fall; 13(3): 401–4PubMedCrossRefGoogle Scholar
  82. 82.
    Mandoki MW. Risperidone treatment of children and adolescents: increased risk of extrapyramidal side effects? J Child Adolesc Psychopharmacol 1995; 5: 49–67CrossRefGoogle Scholar
  83. 83.
    Simeon JG, Carrey NJ, Wiggins DM. Risperidone effects in treatment resistant adolescents: preliminary case reports. J Child Adolesc Psychopharmacol 1995; 5: 69–79CrossRefGoogle Scholar
  84. 84.
    Sternlicht HC, Wells SR. Risperidone in childhood schizophrenia. J Am Acad Child Adolesc Psychiatry 1995 May; 34(5): 540PubMedCrossRefGoogle Scholar
  85. 85.
    Quintana H, Keshavan M. Case study: risperidone in children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 1995 Oct; 34(10): 1292–6PubMedCrossRefGoogle Scholar
  86. 86.
    Lykes WC, Cueva JE. Risperidone in children with schizophrenia. J Am Acad Child Adolesc Psychiatry 1996 Apr; 35(4): 405–6PubMedCrossRefGoogle Scholar
  87. 87.
    Sourander A. Risperidone for treatment of childhood schizophrenia. Am J Psychiatry 1997; 154(10): 1476PubMedGoogle Scholar
  88. 88.
    Grcevich SJ, Findling RL, Rowane WA, et al. Risperidone in the treatment of children and adolescents with schizophrenia: a retrospective study. J Child Adolesc Psychopharmacol 1996 Winter; 6(4): 251–7PubMedCrossRefGoogle Scholar
  89. 89.
    Mandoki M. Olanzapine in the treatment of early-onset schizophrenia: an open label study of olanzapine in adolescents [abstract]. Biol Psychiatry 1997; 41Suppl. 7S: 22SGoogle Scholar
  90. 90.
    Krishnamoorthy J, King BH. Open-label olanzapine treatment in five preadolescent children. J Child Adolesc Psychopharmacol 1998; 8(2): 107–13PubMedCrossRefGoogle Scholar
  91. 91.
    Sholevar EH, Baron DA, Hardie TL. Treatment of childhood-onset schizophrenia with olanzapine. J Child Adolesc Psychopharmacol 2000 Summer; 10(2): 69–78PubMedCrossRefGoogle Scholar
  92. 92.
    Ross RG, Novins D, Farley GK, et al. A 1-year open-label trial of olanzapine in school-age children with schizophrenia. J Child Adolesc Psychopharmacol 2003 Fall; 13(3): 301–9PubMedCrossRefGoogle Scholar
  93. 93.
    Mozes T, Greenberg Y, Spivak B, et al. Olanzapine treatment in chronic drug-resistant childhood onset schizophrenia: an open label study. J Child Adolesc Psychopharmacol 2003 Fall; 13(3): 311–7PubMedCrossRefGoogle Scholar
  94. 94.
    Patel NC, Sierk P, Dorson PG, et al. Experience with ziprasidone [letter]. J Am Acad Child Adolesc Psychiatry 2002 May; 41(5): 495PubMedCrossRefGoogle Scholar
  95. 95.
    McConville B, Carrero L, Sweitzed D, et al. Long-term safety, tolerability, and clinical efficacy of quetiapine in adolescents: an open-label extension trial. J Child Adolesc Psychopharmacol 2003; 13(1): 75–82PubMedCrossRefGoogle Scholar
  96. 96.
    Shaw JA, Lewis JE, Pascal S, et al. A study of quetiapine: efficacy and tolerability in psychotic adolescents. J Child Adolesc Psychopharmacol 2001; 11(4): 415–24PubMedCrossRefGoogle Scholar
  97. 97.
    Lindsey RL, Kaplan D, Koliatsos V. Aripiprazole and extrapyramidal symptoms. J Am Acad Child Adolesc Psychiatry 2003; 42(11): 1268–9PubMedCrossRefGoogle Scholar
  98. 98.
    Toren P, Ratner S, Laor N, et al. Benefit-risk assessment of atypical antipsychotics in the treatment of schizophrenia and comorbid disorders in children and adolescents. Drug Saf 2004; 27(14): 1136–56CrossRefGoogle Scholar
  99. 99.
    Connor DF, Fletcher KE, Wood JS. Neuroleptic-related dyskinesias in children and adolescents. J Clin Psychiatry 2001 ec; 62(12): 967–74PubMedCrossRefGoogle Scholar
  100. 100.
    Campbell M, Armenteros JL, Malone RP, et al. Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study. J Am Acad Child Adolesc Psychiatry 1997 Jun; 36(6): 835–43PubMedCrossRefGoogle Scholar
  101. 101.
    Grcevich SJ, Melamed L, Richards R, et al. Comparative side effects of atypical antipsychotics in children and adolescent [poster]. International Congress of Schizophrenia Research; 2001 Apr 28–May 2; Whistler (BC)Google Scholar
  102. 102.
    Armenteros JL, Withaker AH, Welikson M, et al. Risperidone in adolescents with schizophrenia: an open pilot study. J Am Acad Child Adolesc Psychiatry 1997 May; 36(5): 694–700PubMedCrossRefGoogle Scholar
  103. 103.
    Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002 Aug; 347(5): 314–21CrossRefGoogle Scholar
  104. 104.
    Shea S, Turgay A, Carroll A, et al. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics 2004 Nov; 114(5): E634–41PubMedCrossRefGoogle Scholar
  105. 105.
    Masi G, Cosenza A, Brovedani P, et al. A three-year naturalistic study of 53 preschool children with pervasive developmental disorder treated with risperidone. J Clin Psychiatry 2003 Sep; 64(9): 1039–47PubMedCrossRefGoogle Scholar
  106. 106.
    Findling RL, Aman MG, Eerdekens M, et al. Long-term, open-label study of risperidone in children with severe disruptive behaviors an below-average IQ. Am J Psychiatry 2004 Apr; 161(4): 677–84PubMedCrossRefGoogle Scholar
  107. 107.
    Kemner C, Willemsen-Swinkels S, DeJonge M, et al. Open-label study of olanzapine in children with pervasive developmental disorders. J Clin Psychopharmacol 2002 Oct; 22(5): 455–60PubMedCrossRefGoogle Scholar
  108. 108.
    Findling RL, McNamara NK, Gracious BL. Pediatric uses of atypical antipsychotic. Expert Opin Pharmacother 2000 Jul; 1(5): 935–45PubMedCrossRefGoogle Scholar
  109. 109.
    Martin A, Scahill L, Anderson GM, et al. Weight and leptin changes among risperidone-treated youths with autism: 6-month prospective data. Am J Psychiatry 2004 Jun; 161(6): 1125–7PubMedCrossRefGoogle Scholar
  110. 110.
    Sporn AL, Bobb AJ, Gogtay N, et al. Hormonal correlates of clozapine-induced weight gain in psychotic children: an exploratory study. J Am Acad Child Adolesc Psychiatry 2005 Sep; 44(9): 925–33PubMedCrossRefGoogle Scholar
  111. 111.
    Wudarsky M, Nicolson R, Hamburger SD, et al. Elevated prolactin in pediatric patients on typical and atypical antipsychotics. J Child Adolesc Psychopharmacol 1999; 9(4): 239–45PubMedCrossRefGoogle Scholar
  112. 112.
    Masi G, Cosenza A, Mucci M. Prolactin levels in young children with pervasive developmental disorders during risperidone treatment. J Child Adolesc Psychopharmacol 2001 Winter; 11(4): 389–94PubMedCrossRefGoogle Scholar
  113. 113.
    Findling RL, Kusumakar V, Daneman D, et al. Prolactin levels during long-term risperidone treatment in children and adolescents. J Clin Psychiatry 2003 Nov; 64(11): 1362–9PubMedCrossRefGoogle Scholar
  114. 114.
    Saito E, Correll CU, Gallelli K, et al. A prospective study of hyperprolactinemia in children and adolescents with atypical antipsychotic agents. J Child Adolesc Psychopharmacol 2004 Fall; 14(3): 350–8PubMedCrossRefGoogle Scholar
  115. 115.
    Frazier JA, Biederman J, Tohen M, et al. A prospective open-label trial of olanzapine monotherapy in children and adolescents with bipolar disorder. J Child Adolesc Psychopharmacol 2001 Fall; 11(3): 239–50PubMedCrossRefGoogle Scholar
  116. 116.
    Alfaro CL, Wudarsky M, Nicolson R, et al. Correlation of antipsychotic and prolactin concentration in children and adolescent acutely treated with haloperidol, clozapine and olanzapine. J Child Adolesc Psychopharmacol 2002 Summer; 12(2): 83–91PubMedCrossRefGoogle Scholar
  117. 117.
    Colao A, Loche S, Cappa M, et al. Prolactinomas in children and adolescents: clinical presentation and long term follow-up. J Clin Endocrinol Metab 1998 Aug; 83(8): 2777–80PubMedCrossRefGoogle Scholar
  118. 118.
    Cohen LG, Biederman J. Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children. J Child Adolesc Psychopharmacol 2001; 11(4): 435–40PubMedCrossRefGoogle Scholar
  119. 119.
    Alvir JM, Lieberman JA, Safferman AZ, et al. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med 1993 Jul; 329(3): 162–7Google Scholar
  120. 120.
    Gerbino-Rosen G, Roofeh D, Tompkins DA, et al. Hematologic adverse events in clozapine-treated children and adolescents. J Am Acad Child Adolesc Psychiatry 2005 Oct; 44(10): 1024–31PubMedCrossRefGoogle Scholar
  121. 121.
    Kodesh A, Finkel B, Lerner AG, et al. Dose-dependent olanzapine-associated leukopenia: three case report. Int Clin Psychopharmacol 2001 Mar; 16(2): 117–9PubMedCrossRefGoogle Scholar
  122. 122.
    Edleman RJ. Risperidone side effects. J Am Acad Child Adolesc Psychiatry 1996 Jan; 35(1): 4–5PubMedCrossRefGoogle Scholar
  123. 123.
    Ruhe HG, Becker HE, Jessum P, et al. Agranulocytosis and granulocitopenia associated with quetiapine. Acta Psychiatr Scand 2001 Oct; 104(4): 311–3PubMedCrossRefGoogle Scholar
  124. 124.
    Small JG, Weber MC, Klapper MH, et al. Rechallenge of late-onset neutropenia with clozapine. J Clin Psychopharmacol 2005; 25(2): 185–6PubMedCrossRefGoogle Scholar
  125. 125.
    Kumra S, Herion D, Jacobsen LK, et al. Case study: Risperidone-induced hepatotoxicity in pediatric patients. J Am Acad Child Adolesc Psychiatry 1997 May; 36(5): 701–5PubMedCrossRefGoogle Scholar
  126. 126.
    Woods SW, Martin A, Spector SG, et al. Effects of development on olanzapine-associated adverse events. J Am Acad Child Adolesc Psychiatry 2002 Dec; 41(12): 1439–46PubMedCrossRefGoogle Scholar
  127. 127.
    Szighety E, Wiznitzer M, Branky LA, et al. Risperidone-induced hepatotoxicity in children and adolescents: a chart review. J Child Adolesc Psychopharmacol 1999; 9(2): 93–8CrossRefGoogle Scholar
  128. 128.
    Landau J, Martin A. Is liver function monitoring warranted during risperidone treatment? J Am Acad Child Adolesc Psychiatry 1998 Oct; 37(10): 1007–8PubMedCrossRefGoogle Scholar
  129. 129.
    Ananth J, Parameswaran S, Gunatilake S, et al. Neuroleptic malignant syndrome and atypical antipsychotic drugs. J Clin Psychiatry 2004; 65(4): 464–70PubMedCrossRefGoogle Scholar
  130. 130.
    Ty EB, Rothner AD. Neuroleptic malignant syndrome in children and adolescents. J Child Neurol 2001 Mar; 16(3): 157–63PubMedGoogle Scholar
  131. 131.
    Robb AS, Chang W, Lee HK, et al. Risperidone-induced neuroleptic malignant syndrome in an adolescent. J Child Adolesc Psycopharmacol 2000 Winter; 10(4): 327–30CrossRefGoogle Scholar
  132. 132.
    Sharma R, Trappier B, Ng YK, et al. Risperidone-induced neuroleptic malignant syndrome. Ann Pharmacother 1996 Jul–Aug; 30(7–8): 775–8PubMedGoogle Scholar
  133. 133.
    Philibert RA, Adam LA, Frank FM, et al. Olanzapine usage associated with neuroleptic malignant syndrome. Psychosomatics 2001 Nov–Dec; 42(6): 528–9PubMedCrossRefGoogle Scholar
  134. 134.
    Aboraya A, Schumacher J, Abdalla E, et al. Neuroleptic malignant syndrome associated with risperidone and olanzapine in first-episode schizophrenia. W V Med J 2002 Mar–Apr; 98(2): 63–5PubMedGoogle Scholar
  135. 135.
    Brown TM. Clozapine, neuroleptic malignant syndrome, and pancerebellar syndrome. Psychosomatics 1999 Nov–Dec; 40(6): 518–20PubMedCrossRefGoogle Scholar
  136. 136.
    Newcomer JW. Abnormalities of glucose metabolism associated with atypical antipsychotic drugs. J Clin Psychiatry 2004; 65Suppl. 18: 36–46PubMedGoogle Scholar
  137. 137.
    Koller E, Malozowski S, Doraiswamy PM. Atypical antipsychotic drugs and hyperglycemia in adolescents. JAMA 2001 Nov; 286(20): 2547–8PubMedCrossRefGoogle Scholar
  138. 138.
    Domon SE, Webber JC. Case report: hyperglycemia and hypertriglyceridemia secondary to olanzapine. J Child Adolesc Psychopharmacol 2001 Fall; 11(3): 285–8PubMedCrossRefGoogle Scholar
  139. 139.
    Bloch Y, Vardi O, Mendlovic S, et al. Hyperglicemia from olanzapine treatment in adolescents. J Child Adolesc Psychopharmacol 2003 Spring; 13(1): 97–102PubMedCrossRefGoogle Scholar
  140. 140.
    Nguyen M, Murphy T. Olanzapine and hypertriglyceridemia. J Am Acad Child Adolesc Psychiatry 2001 Feb; 40(2): 133PubMedCrossRefGoogle Scholar
  141. 141.
    Saito E, Kafantaris V. Can diabetes mellitus be induced by medication? J Child Adolesc Psychopharmacol 2002 Fall; 12(3): 231–6PubMedCrossRefGoogle Scholar
  142. 142.
    Martin A, L’Ecuyer S. Triglyceride, cholesterol and weight changes among risperidone-treated youths: a retrospective study. Eur Child Adolesc Psychiatry 2002 Jun; 11(3): 129–33PubMedCrossRefGoogle Scholar
  143. 143.
    Centorrino F, Price BH, Tuttle M, et al. EEG abnormalities during treatment with typical and atypical antipsychotics. Am J Psychiatry 2002 Jan; 159(1): 109–15PubMedCrossRefGoogle Scholar
  144. 144.
    Frazier JA, Gordon C, McKenna K, et al. An open trial of clozapine in 11 adolescents with childhood-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 1994 Jun; 33(5): 658–63PubMedCrossRefGoogle Scholar
  145. 145.
    Freedman J, Wirshing W, Russell A, et al. Absence status seizures after successful long-term clozapine treatment of an adolescent with schizophrenia. J Child Adolesc Psychopharmacol 1994; 4: 53–62CrossRefGoogle Scholar
  146. 146.
    Turpeinen P. Clozapine in adolescent psychiatric patients. CNS Drugs 1996; 6: 339–40CrossRefGoogle Scholar
  147. 147.
    Kelly DR, Love RC. Ziprasidone and the QTc interval: pharmacokinetic and pharmacodynamic considerations. Psychopharmacol Bull 2001; 35(4): 66–79PubMedGoogle Scholar
  148. 148.
    McDougle CJ, Kem DL, Posey CJ. Case series: use of ziprasidone for maladaptive symptoms in youths with autism. J Am Acad Child Adolesc Psychiatry 2002; 41(8): 921–7PubMedCrossRefGoogle Scholar
  149. 149.
    Sallee FR, Miceli JJ, Tensfeld T, et al. Single-dose pharmacokinetics and safety of ziprasidone in children and adolescents. J Am Acad Child Adolesc Psychiatry 2006; 45(6): 720–8PubMedCrossRefGoogle Scholar
  150. 150.
    Blair J, Scahill L, State M, et al. Electrocardiographic changes in children and adolescents treated with ziprasidone: a prospective study. J Am Acad Child Adolesc Psychiatry 2005; 44(1): 73–9PubMedCrossRefGoogle Scholar
  151. 151.
    Posey DJ, Walsh KH, Wilson GA, et al. Risperidone in the treatment of two very young children with autism. J Child Adolesc Psycopharmacol 1999; 9(4): 273–6CrossRefGoogle Scholar
  152. 152.
    Battaglia J. Pharmacological management of acute agitation. Drugs 2005; 65(9): 1207-22PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.IRCCS Stella Maris, Institute of Child Neurology and PsychiatryPisaItaly

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