Skip to main content
Log in

Children with Schizophrenia

Clinical Picture and Pharmacological Treatment

  • Review Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Table III
Table IV

Similar content being viewed by others

References

  1. Kraepelin E. Dementia praecox and paraphrenia (Barclay RM, translator). 8th ed. Edinburgh: S Livingstone, 1919

    Google Scholar 

  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 2nd ed. Washington, DC: American Psychiatric Association, 1968

    Google Scholar 

  3. Kolvin I. Studies in childhood psychoses: I. Diagnostic criteria and classification. Br J Psychiatry 1971 Apr; 118(545): 381–4

    CAS  Google Scholar 

  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): 601–24

    Article  PubMed  CAS  Google Scholar 

  5. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994

    Google Scholar 

  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): 636–44

    Article  PubMed  CAS  Google Scholar 

  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): 968–76

    Article  PubMed  CAS  Google Scholar 

  8. Russell AT, Bott L, Sammons C. The phenomenology of schizophrenia occurring in childhood. J Am Acad Child Adolesc Psychiatry 1989 May; 28(3): 399–407

    Article  PubMed  CAS  Google Scholar 

  9. Russell AT. The clinical presentation of childhood onset schizophrenia. Schizophr Bull 1994; 20(4): 631–46

    Article  PubMed  CAS  Google Scholar 

  10. Spencer EK, Campbell M. Children with schizophrenia: diagnosis, phenomenology and pharmacotherapy. Schizophr Bull 1994; 20(4): 713–25

    Article  PubMed  CAS  Google Scholar 

  11. Asarnow JR, Tompson MC, Goldstein MJ. Childhood-onset schizophrenia: a follow-up study. Schizophr Bull 1994; 20(4): 599–617

    Article  PubMed  CAS  Google Scholar 

  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): 361–70

    CAS  Google Scholar 

  13. Jacobsen LK, Rapoport JL. Childhood-onset schizophrenia: implication of clinical and neurobiological research. J Child Psychol Psychiatry 1998 Jan; 39(1): 101–3

    Article  PubMed  CAS  Google Scholar 

  14. Nicolson R, Rapoport JL. Childhood onset schizophrenia: rare but worth studying. Biol Psychiatry 1999 Nov; 46(10): 1418–28

    Article  PubMed  CAS  Google Scholar 

  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): 1380–9

    Article  PubMed  CAS  Google Scholar 

  16. Hollis C. Adult outcomes of child- and adolescent-onset schizophrenia: diagnostic stability and predictive validity. Am J Psychiatry 2000 Oct; 157(10): 1652–9

    Article  PubMed  CAS  Google Scholar 

  17. Helgeland MI, Torgersen S. Stability and prediction of schizophrenia from adolescent to adulthood. Eur Child Adolesc Psychiatry 2005 Mar; 14(2): 83–94

    Article  PubMed  Google Scholar 

  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): 395–402

    Article  PubMed  Google Scholar 

  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): 477–88

    Article  PubMed  CAS  Google Scholar 

  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): 1273–83

    Article  PubMed  CAS  Google Scholar 

  21. Hollis C. Child and adolescent (juvenile onset) schizophrenia: a case control study of premorbid developmental impairments. Br J Psychiatry 1995 Apr; 166(4): 489–95

    Article  PubMed  CAS  Google Scholar 

  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): 794–800

    Article  PubMed  CAS  Google Scholar 

  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): 666–72

    Article  PubMed  Google Scholar 

  24. Fish B, Kendler KS. Abnormal infant neurodevelopment predicts schizophrenia spectrum disorders. J Child Adolesc Psychopharmacol 2005 Jun; 15(3): 348–61

    Article  PubMed  Google Scholar 

  25. Watkins J, Asarnow R, Tanguay P. Symptom development in childhood onset schizophrenia. J Child Psychol Psychiatry 1988 Nov; 29(6): 865–78

    Article  PubMed  CAS  Google Scholar 

  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): 457–65

    Article  PubMed  CAS  Google Scholar 

  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): 243–62

    Article  PubMed  CAS  Google Scholar 

  28. Volkmar F, Cohen DJ. Comorbid association of autism and schizophrenia. Am J Psychiatry 1991 Dec; 148(12): 1705–7

    PubMed  CAS  Google Scholar 

  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): 177–83

    Article  PubMed  CAS  Google Scholar 

  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): 989–94

    Article  PubMed  Google Scholar 

  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): 490–5

    Article  PubMed  Google Scholar 

  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): 147–50

    Article  PubMed  CAS  Google Scholar 

  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): 538–45

    Article  PubMed  Google Scholar 

  34. Hollis C. Schizophrenia and allied disorders. In: Rutter M, Taylor E, editors. Child and adolescent psychiatry. 4th ed. Maiden (MA): Blackwell Publishing, 2002: 612–35

    Google Scholar 

  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): 791–8

    Article  PubMed  Google Scholar 

  36. Caplan R. Communication deficits in childhood schizophrenia spectrum disorders. Schizophr Bull 1994; 20(4): 671–83

    Article  PubMed  CAS  Google Scholar 

  37. Asarnow JR, Tompson MC, McGrath E. Annotation: childhood onset schizophrenia: clinical and treatment issues. J Child Psychol Psychiatry 2004 Feb; 45(2): 180–94

    Article  PubMed  Google Scholar 

  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): 1190–6

    Article  PubMed  CAS  Google Scholar 

  39. Eggers C. Schizoaffective disorders in childhood: a follow-up study. J Autism Dev Disord 1989 Jun; 19(2): 327–42

    Article  PubMed  CAS  Google Scholar 

  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): 801–16

    Google Scholar 

  41. Eggers C, Bunk D. The long-term course of childhood-onset schizophrenia: a 42-year follow-up. Schizophr Bull 1997 Apr; 23(1): 105–17

    Article  PubMed  CAS  Google Scholar 

  42. McClellan J, McCurry C. Early onset psychotic disorders: diagnostic stability and clinical characteristics. Eur Child Adolesc Psychiatry 1999; 8Suppl. 1: 113–9

    Google Scholar 

  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): 371–8

    CAS  Google Scholar 

  44. McGee R, Williams S, Poulton R. Hallucinations in nonpsychotic children. J Am Acad Child Adolesc Psychiatry 2000 Jan; 39(1): 12–3

    Article  PubMed  CAS  Google Scholar 

  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): 462–5

    Article  PubMed  Google Scholar 

  46. Chambers WJ, Puig-Antich J, Tabrizi MA, et al. Psychotic symptoms in prepubertal major depressive disorder. Arch Gen Psychiatry 1982 Aug; 39(8): 921–7

    Article  PubMed  CAS  Google Scholar 

  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): 337–45

    Article  PubMed  CAS  Google Scholar 

  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): 461–8

    Article  PubMed  CAS  Google Scholar 

  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): 1046–55

    Article  PubMed  CAS  Google Scholar 

  50. Masi G, Perugi G, Toni C, et al. Attention deficit hyperactivity disorder: bipolar comorbidity in children and adolescents. Bipolar Disord 2006; 8(4): 373–81

    Article  PubMed  Google Scholar 

  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: 163–84

    Google Scholar 

  52. Famularo R, Fenton T, Kinscherff R, et al. Psychiatric comorbidity in childhood post-traumatic stress disorder. Child Abuse Negl 1996 Oct; 20(10): 953–61

    Article  PubMed  CAS  Google Scholar 

  53. Donnelly CL. Pharmacologic treatment approaches for children and adolescents with posttraumatic stress disorder. Child Adolesc Psychiatr Clin N Am 2003 Apr; 12(2): 251–69

    Article  PubMed  Google Scholar 

  54. Wolff S. Schizoid personality in childhood and adult life: III. The childhood picture. Br J Psychiatry 1991 Nov; 159: 629–35

    CAS  Google Scholar 

  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): 954–64

    Article  PubMed  Google Scholar 

  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): 1541–7

    PubMed  CAS  Google Scholar 

  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): 673–81

    Article  PubMed  Google Scholar 

  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): 91–9

    Article  PubMed  CAS  Google Scholar 

  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): 775–82

    Article  PubMed  CAS  Google Scholar 

  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): 319–25

    Article  PubMed  CAS  Google Scholar 

  61. Stayer C, Sporn A, Gogtay N, et al. Multidiniensionally impaired: the good news. J Child Adolesc Psychopharmacol 2005 Jun; 15(3): 510–9

    Article  PubMed  Google Scholar 

  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: 20–39

    Google Scholar 

  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): 911–9

    Article  PubMed  CAS  Google Scholar 

  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): 465–76

    Article  PubMed  Google Scholar 

  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): 1096–106

    Article  PubMed  Google Scholar 

  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): 183–6

    PubMed  CAS  Google Scholar 

  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): 377–85

    Article  PubMed  CAS  Google Scholar 

  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): 133–45

    Article  PubMed  CAS  Google Scholar 

  69. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. revised. Washington, DC: American Psychiatric Association, 1987

    Google Scholar 

  70. Spencer EK, Campbell M. Children with schizophrenia: diagnosis, phenomenology and pharmacotherapy. Schizophr Bull 1994; 20(4): 713–25

    Article  PubMed  CAS  Google Scholar 

  71. Campbell M, Rapoport JL, Simpson GM. Antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 1999 May; 38(5): 537–45

    Article  PubMed  CAS  Google Scholar 

  72. Brenner HD, Dencker SJ, Goldstein MJ, et al. Defining treatment refractoriness in schizophrenia. Schizophr Bull 1990; 16(4): 551–61

    Article  PubMed  CAS  Google Scholar 

  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): 221–7

    Article  PubMed  CAS  Google Scholar 

  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): 1090–7

    Article  PubMed  CAS  Google Scholar 

  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): 651–7

    Article  PubMed  CAS  Google Scholar 

  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): 65–70

    Article  PubMed  CAS  Google Scholar 

  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: 241–53

    Article  Google Scholar 

  78. MacEwan TH, Morton MJ. Use of clozapine in a child with treatment-resistant schizophrenia. Br J Psychiatry 1996 Mar; 168(3): 376–8

    Article  PubMed  CAS  Google Scholar 

  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: 507–10

    Article  PubMed  CAS  Google Scholar 

  80. Gogtay N, Sporn A, Alfaro CL, et al. Clozapine-induced akathisia in children with schizophrenia. J Child Adolesc Psychopharmacol 2002 Winter; 12(4): 347–9

    Article  PubMed  Google Scholar 

  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): 401–4

    Article  PubMed  Google Scholar 

  82. Mandoki MW. Risperidone treatment of children and adolescents: increased risk of extrapyramidal side effects? J Child Adolesc Psychopharmacol 1995; 5: 49–67

    Article  Google Scholar 

  83. Simeon JG, Carrey NJ, Wiggins DM. Risperidone effects in treatment resistant adolescents: preliminary case reports. J Child Adolesc Psychopharmacol 1995; 5: 69–79

    Article  Google Scholar 

  84. Sternlicht HC, Wells SR. Risperidone in childhood schizophrenia. J Am Acad Child Adolesc Psychiatry 1995 May; 34(5): 540

    Article  PubMed  CAS  Google Scholar 

  85. Quintana H, Keshavan M. Case study: risperidone in children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 1995 Oct; 34(10): 1292–6

    Article  PubMed  CAS  Google Scholar 

  86. Lykes WC, Cueva JE. Risperidone in children with schizophrenia. J Am Acad Child Adolesc Psychiatry 1996 Apr; 35(4): 405–6

    Article  PubMed  CAS  Google Scholar 

  87. Sourander A. Risperidone for treatment of childhood schizophrenia. Am J Psychiatry 1997; 154(10): 1476

    PubMed  CAS  Google Scholar 

  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): 251–7

    Article  PubMed  CAS  Google Scholar 

  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: 22S

    Google Scholar 

  90. Krishnamoorthy J, King BH. Open-label olanzapine treatment in five preadolescent children. J Child Adolesc Psychopharmacol 1998; 8(2): 107–13

    Article  PubMed  CAS  Google Scholar 

  91. Sholevar EH, Baron DA, Hardie TL. Treatment of childhood-onset schizophrenia with olanzapine. J Child Adolesc Psychopharmacol 2000 Summer; 10(2): 69–78

    Article  PubMed  CAS  Google Scholar 

  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): 301–9

    Article  PubMed  Google Scholar 

  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): 311–7

    Article  PubMed  Google Scholar 

  94. Patel NC, Sierk P, Dorson PG, et al. Experience with ziprasidone [letter]. J Am Acad Child Adolesc Psychiatry 2002 May; 41(5): 495

    Article  PubMed  Google Scholar 

  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): 75–82

    Article  PubMed  Google Scholar 

  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): 415–24

    Article  PubMed  CAS  Google Scholar 

  97. Lindsey RL, Kaplan D, Koliatsos V. Aripiprazole and extrapyramidal symptoms. J Am Acad Child Adolesc Psychiatry 2003; 42(11): 1268–9

    Article  PubMed  Google Scholar 

  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): 1136–56

    Article  Google Scholar 

  99. Connor DF, Fletcher KE, Wood JS. Neuroleptic-related dyskinesias in children and adolescents. J Clin Psychiatry 2001 ec; 62(12): 967–74

    Article  PubMed  CAS  Google Scholar 

  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): 835–43

    Article  PubMed  CAS  Google Scholar 

  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)

  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): 694–700

    Article  PubMed  CAS  Google Scholar 

  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): 314–21

    Article  Google Scholar 

  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): E634–41

    Article  PubMed  Google Scholar 

  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): 1039–47

    Article  PubMed  CAS  Google Scholar 

  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): 677–84

    Article  PubMed  Google Scholar 

  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): 455–60

    Article  PubMed  CAS  Google Scholar 

  108. Findling RL, McNamara NK, Gracious BL. Pediatric uses of atypical antipsychotic. Expert Opin Pharmacother 2000 Jul; 1(5): 935–45

    Article  PubMed  CAS  Google Scholar 

  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): 1125–7

    Article  PubMed  Google Scholar 

  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): 925–33

    Article  PubMed  Google Scholar 

  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): 239–45

    Article  PubMed  CAS  Google Scholar 

  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): 389–94

    Article  PubMed  CAS  Google Scholar 

  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): 1362–9

    Article  PubMed  CAS  Google Scholar 

  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): 350–8

    Article  PubMed  Google Scholar 

  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): 239–50

    Article  PubMed  CAS  Google Scholar 

  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): 83–91

    Article  PubMed  Google Scholar 

  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): 2777–80

    Article  PubMed  CAS  Google Scholar 

  118. Cohen LG, Biederman J. Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children. J Child Adolesc Psychopharmacol 2001; 11(4): 435–40

    Article  PubMed  CAS  Google Scholar 

  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): 162–7

    CAS  Google Scholar 

  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): 1024–31

    Article  PubMed  Google Scholar 

  121. Kodesh A, Finkel B, Lerner AG, et al. Dose-dependent olanzapine-associated leukopenia: three case report. Int Clin Psychopharmacol 2001 Mar; 16(2): 117–9

    Article  PubMed  CAS  Google Scholar 

  122. Edleman RJ. Risperidone side effects. J Am Acad Child Adolesc Psychiatry 1996 Jan; 35(1): 4–5

    Article  PubMed  CAS  Google Scholar 

  123. Ruhe HG, Becker HE, Jessum P, et al. Agranulocytosis and granulocitopenia associated with quetiapine. Acta Psychiatr Scand 2001 Oct; 104(4): 311–3

    Article  PubMed  CAS  Google Scholar 

  124. Small JG, Weber MC, Klapper MH, et al. Rechallenge of late-onset neutropenia with clozapine. J Clin Psychopharmacol 2005; 25(2): 185–6

    Article  PubMed  Google Scholar 

  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): 701–5

    Article  PubMed  CAS  Google Scholar 

  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): 1439–46

    Article  PubMed  Google Scholar 

  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): 93–8

    Article  Google Scholar 

  128. Landau J, Martin A. Is liver function monitoring warranted during risperidone treatment? J Am Acad Child Adolesc Psychiatry 1998 Oct; 37(10): 1007–8

    Article  PubMed  CAS  Google Scholar 

  129. Ananth J, Parameswaran S, Gunatilake S, et al. Neuroleptic malignant syndrome and atypical antipsychotic drugs. J Clin Psychiatry 2004; 65(4): 464–70

    Article  PubMed  CAS  Google Scholar 

  130. Ty EB, Rothner AD. Neuroleptic malignant syndrome in children and adolescents. J Child Neurol 2001 Mar; 16(3): 157–63

    PubMed  CAS  Google Scholar 

  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): 327–30

    Article  CAS  Google Scholar 

  132. Sharma R, Trappier B, Ng YK, et al. Risperidone-induced neuroleptic malignant syndrome. Ann Pharmacother 1996 Jul–Aug; 30(7–8): 775–8

    PubMed  CAS  Google Scholar 

  133. Philibert RA, Adam LA, Frank FM, et al. Olanzapine usage associated with neuroleptic malignant syndrome. Psychosomatics 2001 Nov–Dec; 42(6): 528–9

    Article  PubMed  CAS  Google Scholar 

  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): 63–5

    PubMed  Google Scholar 

  135. Brown TM. Clozapine, neuroleptic malignant syndrome, and pancerebellar syndrome. Psychosomatics 1999 Nov–Dec; 40(6): 518–20

    Article  PubMed  CAS  Google Scholar 

  136. Newcomer JW. Abnormalities of glucose metabolism associated with atypical antipsychotic drugs. J Clin Psychiatry 2004; 65Suppl. 18: 36–46

    PubMed  CAS  Google Scholar 

  137. Koller E, Malozowski S, Doraiswamy PM. Atypical antipsychotic drugs and hyperglycemia in adolescents. JAMA 2001 Nov; 286(20): 2547–8

    Article  PubMed  CAS  Google Scholar 

  138. Domon SE, Webber JC. Case report: hyperglycemia and hypertriglyceridemia secondary to olanzapine. J Child Adolesc Psychopharmacol 2001 Fall; 11(3): 285–8

    Article  PubMed  CAS  Google Scholar 

  139. Bloch Y, Vardi O, Mendlovic S, et al. Hyperglicemia from olanzapine treatment in adolescents. J Child Adolesc Psychopharmacol 2003 Spring; 13(1): 97–102

    Article  PubMed  Google Scholar 

  140. Nguyen M, Murphy T. Olanzapine and hypertriglyceridemia. J Am Acad Child Adolesc Psychiatry 2001 Feb; 40(2): 133

    Article  PubMed  CAS  Google Scholar 

  141. Saito E, Kafantaris V. Can diabetes mellitus be induced by medication? J Child Adolesc Psychopharmacol 2002 Fall; 12(3): 231–6

    Article  PubMed  Google Scholar 

  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): 129–33

    Article  PubMed  CAS  Google Scholar 

  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): 109–15

    Article  PubMed  Google Scholar 

  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): 658–63

    Article  PubMed  CAS  Google Scholar 

  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: 53–62

    Article  Google Scholar 

  146. Turpeinen P. Clozapine in adolescent psychiatric patients. CNS Drugs 1996; 6: 339–40

    Article  Google Scholar 

  147. Kelly DR, Love RC. Ziprasidone and the QTc interval: pharmacokinetic and pharmacodynamic considerations. Psychopharmacol Bull 2001; 35(4): 66–79

    PubMed  CAS  Google Scholar 

  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): 921–7

    Article  PubMed  Google Scholar 

  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): 720–8

    Article  PubMed  Google Scholar 

  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): 73–9

    Article  PubMed  Google Scholar 

  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): 273–6

    Article  CAS  Google Scholar 

  152. Battaglia J. Pharmacological management of acute agitation. Drugs 2005; 65(9): 1207-22

    Article  PubMed  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gabriele Mast.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mast, G., Mucci, M. & Pari, C. Children with Schizophrenia. CNS Drugs 20, 841–866 (2006). https://doi.org/10.2165/00023210-200620100-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-200620100-00005

Keywords

Navigation