, Volume 71, Issue 2, pp 179–208 | Cite as

Management of Schizophrenia in Children and Adolescents

Focus on Pharmacotherapy
Review Article


Schizophrenia in subjects younger than 13 years is defined as very-early-onset schizophrenia, and its prevalence is estimated at 1 in 10000, while early-onset schizophrenia occurs between 13 and 17 years, and its prevalence is about 0.5%. Only a minority of youths show a complete recovery, and the majority of patients present a moderate to severe impairment at the outset. Treatment of schizophrenia always needs both pharmacological and nonpharmacological interventions. Nonpharmacological interventions include counselling for the patients and the family, psychological support, behavioural treatments, social and cognitive rehabilitation, assistance in social and scholastic activities, enhancement of social skills and family support. Pharmacological treatment is necessary for remission and control of positive and negative symptoms. Furthermore, proper pharmacotherapy can greatly increase the efficacy of psychosocial interventions. Available literature on pharmacotherapy in children and adolescents with schizophrenia is critically reviewed, including both first-and second-generation antipsychotics. Data on efficacy and safety are reported for all the marketed atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole), based on randomized, placebo-controlled studies and the most relevant open-label or naturalistic studies. Adverse effects of concern are closely analysed, such as extrapyramidal side effects and tardive dyskinesia, metabolic syndrome (including hyperglycaemia and hyperlipidaemia), weight gain, hyperprolactinaemia, hepatotoxicity, seizures, and cardiovascular and haematological adverse effects. Finally, practical guidelines for the management of specific clinical situations are provided: the first phases and the long-term approach to pharmacotherapy, the treatment refractoriness and the use of clozapine in youths, the agitated adolescent and the treatment of negative symptoms and of affective co-morbidity. Current experience indicates that, based on low rates of remission, low effect size of medications and frequent adverse effects, mainly metabolic syndrome, further research is warranted, with both randomized, placebo-controlled studies and long-term, naturalistic follow-up of large samples of patients with different age ranges.



No sources of funding were used in the preparation of this review. Dr Liboni has no conflicts of interest that are relevant to the content of this review. Dr Masi is a consultant for Eli Lilly, Shire and Novartis, has received research grants from Eli Lilly, and has been a speaker for Eli Lilly, GlaxoSmithKline, Sanofi-Aventis, Janssen Cilag and AstraZeneca.


  1. 1.
    Madaan V, Dvir Y, Wilson DR. Child and adolescent schizophrenia: pharmacological approach. Expert Opin Pharmacother 2008 Aug; 9(12): 2053–68PubMedGoogle Scholar
  2. 2.
    Werry JS. Child and adolescent (early onset) schizophrenia: a review in light of DSM-III-R. J Autism Dev Disord 1992 Dec; 22(4): 601–24PubMedGoogle Scholar
  3. 3.
    Asarnow JR, Tompson MC, McGrath E. Annotation: childhood-onset schizophrenia: clinical and treatment issues. J Child Psychol Psychiatry 2004 Feb; 45(2): 180–94PubMedGoogle Scholar
  4. 4.
    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): 794–800PubMedGoogle Scholar
  5. 5.
    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): 666–72PubMedGoogle Scholar
  6. 6.
    Masi G, Mucci M, Pari C. Children with schizophrenia: clinical picture and pharmacological treatment. CNS Drugs 2006; 20(10): 841–66PubMedGoogle Scholar
  7. 7.
    Nicolson R, Rapoport JL. Childhood-onset schizophrenia: rare, but worth studying. Biol Psychiatry 1999 Nov 15; 46(10): 1418–28PubMedGoogle Scholar
  8. 8.
    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): 490–5PubMedGoogle Scholar
  9. 9.
    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): 636–44PubMedGoogle Scholar
  10. 10.
    Kumra S, Jacobsen LK, Lenane M, et al. ‘Multi-dimensionally impaired disorder’: is it a variant of very early onset schizophrenia? J Am Acad Child Adolesc Psychiatry 1998 Jan; 37(1): 91–9PubMedGoogle Scholar
  11. 11.
    Werry JS, McClellan J, Chard L. Early-onset schizophrenia, bipolar and schizoaffective disorders: a clinical follow-up study. J Am Acad Child Adolesc Psychiatry 1991 May; 30(3): 457–65PubMedGoogle Scholar
  12. 12.
    McClellan JM, 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): 243–62PubMedGoogle Scholar
  13. 13.
    Maziade M, Gingras N, Rodrigue C, 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): 361–70PubMedGoogle Scholar
  14. 14.
    Maziade M, Bouchard S, 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): 371–8PubMedGoogle Scholar
  15. 15.
    Eggers C, Bunk D. The long-term course of childhood-onset schizophrenia: a 42-year follow-up. Schizophr Bull 1997; 23(1): 105–17PubMedGoogle 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): 1652–9PubMedGoogle Scholar
  17. 17.
    Petersen L, Jeppesen P, Thorup A, et al. A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ 2005 Sep 17; 331: 602PubMedCentralPubMedGoogle Scholar
  18. 18.
    Eack SM, Greenwald DP, Hogarty SS, et al. Cognitive enhancement therapy for early course of schizophrenia: effect of a two-year randomized controlled trial. Psychiatr Serv 2009 Nov; 60(11): 1468–76PubMedCentralPubMedGoogle Scholar
  19. 19.
    Kumra S, Oberstar JV, Sikich L, et al. Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia. Schizophr Bull 2008; 34(1): 60–71PubMedCentralPubMedGoogle Scholar
  20. 20.
    Fraguas D, Correll CU, Merchàn-Naranjo J, et al. 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 Neuro-psychopharmacol. Epub 2010 Aug 9Google Scholar
  21. 21.
    Pool D, Bloom W, Mielke DH, et al. A controlled evaluation of loxitane in seventy-five adolescent schizophrenic patients. Curr Ther Res Clin Exp 1976 Jan; 19(1): 99–104PubMedGoogle Scholar
  22. 22.
    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
  23. 23.
    Spencer EK, Campbell M. Children with schizophrenia: diagnosis, phenomenology and pharmacotherapy. Schizophr Bull 1994; 20(4): 713–25PubMedGoogle Scholar
  24. 24.
    Realmuto GM, Erickson WD, Yellin AM, et al. Clinical comparison of thiothixene and thioridazine in schizophrenic adolescents. Am J Psychiatry 1984 Mar; 141(3): 440–2PubMedGoogle Scholar
  25. 25.
    Kumra S, Frazier J, Jacobsen LK, et al. Childhood onset schizophrenia: a double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry 1996 Dec; 53(12): 1090–7PubMedGoogle Scholar
  26. 26.
    Shaw P, Sporn A, Gogtay N, et al. Childhood-onset schizophrenia: a double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry 2006 Jul; 63(7): 721–30PubMedGoogle Scholar
  27. 27.
    Kumra S, Kranzler H, Gerbino-Rosen G, et al. Clozapine and ‘high dose’ olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison. Biol Psychiatry 2008 Mar 1; 63(5): 221–7Google Scholar
  28. 28.
    Haas M, Eerdekens M, Kushner L, et al. Efficacy, safety and tolerability of two dosing regimens in adolescent schizophrenia: a double-blind study. Br J Psychiatry 2009 Feb; 194(2): 158–64PubMedGoogle Scholar
  29. 29.
    Haas M, Unis AS, Armenteros J, et al. A 6-week, randomized, double blind placebo-controlled study of the efficacy and safety of risperidone in adolescent with schizophrenia. J Child Adolesc Psychopharmacol 2009 Dec; 19(6): 611–21PubMedGoogle Scholar
  30. 30.
    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): 133–45PubMedGoogle Scholar
  31. 31.
    Sikich L, Frazier JA, McClellan J, et al. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizoaffective disorder: findings from the treatment of early-onset schizophrenia spectrum disorder (TEOSS) study. Am J Psychiatry 2008 Nov; 165(11): 1420–31PubMedGoogle Scholar
  32. 32.
    Kryzhanovskaya L, Schulz SC, McDougle 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 Jan; 48(1): 60–70PubMedGoogle Scholar
  33. 33.
    Findling R, Robb A, Nyilas M, et al. A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. Am J Psychiatry 2008 Nov; 165(11): 1432–41PubMedGoogle Scholar
  34. 34.
    Kane J, Honigfeld G, Singer J, et al. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988 Sep; 45(9): 789–96PubMedGoogle Scholar
  35. 35.
    Meltzer HY, Alphs L, Green AI, et al., International Suicide Prevention Trial Study Group. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003 Jan; 60(1): 82–91PubMedGoogle Scholar
  36. 36.
    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 15; 329(3): 162–7PubMedGoogle Scholar
  37. 37.
    Frazier JA, Gordon CT, 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: 658–63PubMedGoogle Scholar
  38. 38.
    Kranzler H, Roofeh D, Gerbino-Rosen G, et al. Clozapine: its impact on aggressive behavior among children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 2005 Jan; 44(1): 55–63PubMedGoogle Scholar
  39. 39.
    Sporn AL, Vermani A, Greenstein DK, et al. Clozapine treatment of childhood-onset schizophrenia: evaluation of effectiveness, adverse effects, and long-term outcome. J Am Acad Child Adolesc Psychiatry 2007 Oct; 46(10): 1349–56PubMedGoogle Scholar
  40. 40.
    Kim Y, Kim BN, Cho SC, et al. Long-term sustained benefits of clozapine treatment in refractory early-onset schizophrenia: a retrospective study in Korean children and adolescents. Hum Psychopharmacol 2008 Dec; 23(8): 715–22PubMedGoogle Scholar
  41. 41.
    Lindenmayer JP, Eerdekens E, Berry SA, et al. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J Clin Psychiatry 2004 Aug; 65(8): 1084–9PubMedGoogle Scholar
  42. 42.
    Weiden PJ, Schooler NR, Weedon JC, et al. A randomized controlled trial of long-acting injectable risperidone vs continuation on oral atypical antipsychotics for first-episode schizophrenia patients: initial adherence outcome. J Clin Psychiatry 2009; 70(10): 1397–406PubMedGoogle Scholar
  43. 43.
    Chwieduk CM, Keating GM. Paliperidone: a review of its use in the management of schizophrenia. Drugs 2010 Jul 9; 70(10): 1295–317PubMedGoogle Scholar
  44. 44.
    Canuso CM, Bossie CA, Turkoz I, et al. Paliperidone extended release for schizophrenia: effects on symptoms and functioning in acutely ill patients with negative symptoms. Schizophr Res 2009 Aug; 113(1): 56–64PubMedGoogle Scholar
  45. 45.
    Stigler KA, Erickson CA, Mullett JE, et al. Paliperidone for irritability in autistic disorder. J Child Adolesc Psychopharmacol 2010 Feb; 20(1): 75–8PubMedGoogle Scholar
  46. 46.
    McConville B, Carrero L, Sweitzer D, et al. Long-term safety, tolerability, and clinical efficacy of quetiapine in adolescents: an open-label extension trial. J Child Adolesc Psychopharmacology 2003 Spring; 13(1): 75–82Google Scholar
  47. 47.
    Dittmann RW, Meyer E, Freisleder FJ, 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 Feb; 18(1): 54–69PubMedGoogle Scholar
  48. 48.
    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): 301–9PubMedGoogle Scholar
  49. 49.
    Grothe DR, Calis KA, Jacobsen L, et al. Olanzapine pharmacokinetics in pediatric and adolescent inpatients with childhood-onset schizophrenia. J Clin Psychopharmacol 2000 Apr; 20(2): 220–5PubMedGoogle Scholar
  50. 50.
    Schimmelmann BG, Mehler-Wex C, Lambert M, et al. A prospective 12-week study of quetiapine in adolescents with schizophrenia spectrum disorders. J Child Adolesc Psychopharmacol 2007 Dec; 17(6): 768–78PubMedGoogle Scholar
  51. 51.
    McConville BJ, Arvanitis LA, Thyrum PT, et al. Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders. J Clin Psychiatry 2000 Apr; 61(4): 252–60PubMedGoogle Scholar
  52. 52.
    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 Jan; 44(1): 73–9PubMedGoogle Scholar
  53. 53.
    Patel NC, Sierk P, Dorson PG, et al. Experience with ziprasidone [letter]. J Am Acad Child Adolesc Psychiatry 2002 May; 41(5): 495PubMedGoogle Scholar
  54. 54.
    Sallee FR, Gilbert DL, Vinks AA, et al. Pharmacodynamics of ziprasidone in children and adolescents: impact on dopamine transmission. J Am Acad Child Adolesc Psychiatry 2003 Aug; 42(8): 902–7PubMedGoogle Scholar
  55. 55.
    Staller JA. Intramuscular ziprasidone in youth: a retrospective chart review. J Child Adolesc Psychopharmacol 2004 Winter; 14(4): 590–2PubMedGoogle Scholar
  56. 56.
    Barzman DH, DelBello MP, Forrester JJ, et al. A retrospective chart review of intramuscular ziprasidone for agitation of children and adolescents on psychiatric units: prospective studies are needed. J Child Adolesc Psychopharmacol 2007 Aug; 17(4): 503–9PubMedGoogle Scholar
  57. 57.
    Bachmann CJ, Lehr D, Theisen FM, et al. Aripiprazole as an adjunct to clozapine therapy in adolescents with early-onset schizophrenia: a retrospective chart review. Pharmacopsychiatry 2009 Jul; 42(4): 153–7PubMedGoogle Scholar
  58. 58.
    Bachmann CJ, Rieger-Gies A, Heinzel Gutenbrunner M, et al. Large variability of aripiprazole and dehydroaripiprazole serum concentrations in adolescent patients with schizophrenia. Ther Drug Monitor 2008 Aug; 30(4): 462–6Google Scholar
  59. 59.
    Findling RL, Johnson JL, McClellan J, et al. Double-blind maintenance safety and effectiveness findings from the treatment of early-onset schizophrenia spectrum (TEOSS) disorders. J Am Acad Child Adolesc Psychiatry 2010 Jun; 49(6): 583–94PubMedCentralPubMedGoogle Scholar
  60. 60.
    Gothelf D, Apter A, Reidman J, et al. Olanzapine, risperidone and haloperidol in the treatment of adolescent patients with schizophrenia. J Neural Transm 2003; 110: 545–60PubMedGoogle Scholar
  61. 61.
    Mozes T, Ebert T, Michal SE, et al. An open label, randomized comparison of of olanzapine versus risperidone in the treatment of childhood-onset schizophrenia. J Child Adolesc Psychopharmacol 2006 Aug; 16(4): 393–403PubMedGoogle Scholar
  62. 62.
    Jensen JB, Kumra S, Leitten W, et al. A comparative pilot study of second generation antipsychotics in children and adolescents with schizophrenia spectrum disorder. J Child Adolesc Psychopharmacol 2008; 18: 317–26PubMedGoogle Scholar
  63. 63.
    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: 26–36PubMedGoogle Scholar
  64. 64.
    Jerrell JM, McIntyre RS. Adverse events in children and adolescents treated with antipsychotic medications. Hum Psychopharmacol 2008 Jun; 23(4): 283–90PubMedGoogle Scholar
  65. 65.
    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): 221–7PubMedGoogle Scholar
  66. 66.
    Correll CU, Kane JM. One-year incidence rates of tardive dyskinesia in children and adolescents treated with second generation of antipsychotic: a systematic review. J Child Adolesc Psychopharmacol 2007 Oct; 17(5): 647–56PubMedGoogle Scholar
  67. 67.
    Theisen FM, Linden A, Geller F, et al. Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relationship to antipsychotic medication. J Psychiatr Res 2001 Nov–Dec; 35(6): 339–45PubMedGoogle Scholar
  68. 68.
    Baptista T, Kin NM, Beaulieu S, et al. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanism, management and research perspectives. Pharmacopsychiatry 2002 Nov; 35(6): 205–19PubMedGoogle Scholar
  69. 69.
    Correll CU, Carlson HE. Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psychiatry 2006 Jul; 45(7): 771–91PubMedGoogle Scholar
  70. 70.
    Weiss R, Dziura J, Burgert DS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004 Jun 3; 350(23): 2362–74PubMedGoogle Scholar
  71. 71.
    Ratzoni G, Gothelf D, Brand-Gothelf A, et al. Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study. J Am Acad Child Adolesc Psychiatry 2002 Mar; 41(3): 337–43PubMedGoogle Scholar
  72. 72.
    Fleischhacker C, Heiser P, Hennonghausen P, et al. Weight gain in children and adolescents during 45 weeks treatment with clozapine, olanzapine and risperidone. J Neural Transm 2008; 115(11): 1599–608Google Scholar
  73. 73.
    Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009 Oct 28; 302(16): 1765–73PubMedCentralPubMedGoogle Scholar
  74. 74.
    Lessig MC, Shapira NA, Murphy TK. Topiramate for reversing atypical antipsychotic weight gain [letter]. J Am Acad Child Adolesc Psychiatry 2001 Dec; 40(12): 1364PubMedGoogle Scholar
  75. 75.
    Pavuluri MN, Janicak PG, Carbray J. Topiramate plus risperidone for controlling weight gain and symptoms in preschool mania. J Child Adolesc Psychopharmacol 2002 Fall; 12(3): 271–3PubMedGoogle Scholar
  76. 76.
    Wu RR, Zhao JP. Metformin addition attenuates olanzapine-induced weight gain in drug-naïve first episode schizophrenia patients: a double-blind, placebo-controlled study. Am J Psychiatry 2008 Mar; 165(3): 352–8PubMedGoogle Scholar
  77. 77.
    Wu RR, Zhao JP. Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain: a randomized controlled trial. JAMA 2008 Jan 9; 299(2): 185–93PubMedGoogle Scholar
  78. 78.
    Newcomer JW. Abnormalities of glucose metabolism associated with atypical antipsychotic drugs. J Clin Psychiatry 2004; 65 Suppl. 18: 36–46PubMedGoogle Scholar
  79. 79.
    Morrato EH, Nicol GE, Maahs D, et al. Metabolic screening in children receiving antipsychotic drug treatment. Arch Ped Adolesc Med 2010; 164: 344–51Google Scholar
  80. 80.
    Koller E, Malozowski S, Doraiswamy PM. Atypical antipsychotic drugs and hyperglycemia in adolescents. JAMA 2001 Nov 28; 286(20): 2547–8PubMedGoogle Scholar
  81. 81.
    Koller EA, Cross JT, Schneider B. Risperidone-associated diabetes mellitus in children. Pediatrics 2004 Feb; 113(2): 421–2PubMedGoogle Scholar
  82. 82.
    Bloch Y, Vardi O, Mendlovic S, et al. Hyperglicemia from olanzapine treatment in adolescents. J Child Adolescent Psychopharmacol 2003 Spring; 13(1): 97–102Google Scholar
  83. 83.
    Saito E, Kafantaris V. Can diabetes mellitus be induced by medication? J Child Adolesc Psychopharmacol 2002 Fall; 12(3): 231–6PubMedGoogle Scholar
  84. 84.
    Cohen D, Huinink S. Atypical antipsychotic-induced diabetes mellitus in child and adolescent psychiatry. CNS Drugs 2007; 21(12): 1035–8PubMedGoogle Scholar
  85. 85.
    Regenold WT, Thapar RK, Marano C, et al. Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and schizoaffective disorders independent of psychotropic drug use. J Affect Disord 2002; 70: 19–26PubMedGoogle Scholar
  86. 86.
    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): 239–45PubMedGoogle Scholar
  87. 87.
    Masi G, Cosenza A, Mucci M. Prolactin levels in preschool autistic children during risperidone treatment. J Child Adolesc Psychopharmacol 2001 Winter; 11(4): 389–94PubMedGoogle Scholar
  88. 88.
    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): 1039–47PubMedGoogle Scholar
  89. 89.
    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): 1362–9PubMedGoogle Scholar
  90. 90.
    Saito E, Correll CU, Gallelli K, et al. A prospective study of hyperprolactinemia in children and adolescents treated with atypical antipsychotic agents. J Child Adolesc Psychopharmacol 2004 Fall; 14(3): 350–8PubMedGoogle Scholar
  91. 91.
    Alfaro CL, Wudarsky M, Nicolson R, et al. Correlation of antipsychotic and prolactin concentrations in children and adolescents acutely treated with haloperidol, clozapine, or olanzapine. J Child Adolesc Psychopharmacol 2002; 12: 83–91PubMedGoogle Scholar
  92. 92.
    Kinon BJ, Gilmore JA, Liu H, et al. Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trial. Psychoneuroendocrinology 2003 Apr; 28 Suppl. 2: 69–82PubMedGoogle Scholar
  93. 93.
    Szarfman A, Tonning JM, Levine JG, et al. Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy 2006 Jun; 26(6): 748–58PubMedGoogle Scholar
  94. 94.
    Oyama K, Sanno N, Tahara S, et al. Management of pituitary incidentalomas: according to a survey of pituitary incidentalomas in Japan. Semin Ultrasound CT MR 2005 Feb; 26(1): 47–50PubMedGoogle Scholar
  95. 95.
    Cohen LG, Biederman J. Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children. J Child Adolesc Psychopharmacol 2001 Winter; 11(4): 435–40PubMedGoogle Scholar
  96. 96.
    Wahl R, Ostroff R. Reversal of symptomatic hyperprolactinemia by aripiprazole. Am J Psychiatry 2005 Aug; 162(8): 1542–3PubMedGoogle Scholar
  97. 97.
    Ty EB, Rothner AD. Neuroleptic malignant syndrome in children and adolescents. J Child Neurol 2001 Mar; 16(3): 157–63PubMedGoogle Scholar
  98. 98.
    Silva RR, Munoz DM, Alpert M, et al. Neuroleptic malignant syndrome in children and adolescents. J Am Acad Child Adolesc Psychiatry 1999 Feb; 38(2): 187–94PubMedGoogle Scholar
  99. 99.
    Sachdev P, Kruk J, Kneebone M, et al. Clozapine-induced neuroleptic malignant syndrome: review and report of new cases. J Clin Psychopharmacol 1995 Oct; 15(5): 365–71PubMedGoogle Scholar
  100. 100.
    Palakurthi HB, Parvin MM, Kaplan S. Neuroleptic malignant syndrome from aripiprazole in an agitated pediatric patient. Clin Neuropharmacol 2007 Jan–Feb; 30(1): 47–51PubMedGoogle Scholar
  101. 101.
    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): 1024–31PubMedGoogle Scholar
  102. 102.
    Kodesh A, Finkel B, Lerner AG, et al. Dose-dependent olanzapine-associated leukopenia: three case reports. Int Clin Psychopharmacol 2001 Mar; 16(2): 117–9PubMedGoogle Scholar
  103. 103.
    Ruhé HG, Becker HE, Jessurun P, et al. Agranulocytosis and granulocytopenia associated with quetiapine. Acta Psychiatr Scand 2001 Oct; 104(4): 311–3PubMedGoogle Scholar
  104. 104.
    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): 401–4PubMedGoogle Scholar
  105. 105.
    Gagliano A, Masi G. Clozapine-aripiprazole association in a 7-year old girl with schizophrenia and successful management of neutropenia with lithium. J Child Adolesc Psychopharmacol 2009 Oct; 19(5): 595–8PubMedGoogle Scholar
  106. 106.
    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): 701–5PubMedGoogle Scholar
  107. 107.
    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): 1409–11Google Scholar
  108. 108.
    Szigethy E, Wiznitzer M, Branicky LA, et al. Risperidone-induced hepatotoxicity in children and adolescents? A chart review. J Child Adolesc Psychopharmacol 1999; 9(2): 93–8PubMedGoogle Scholar
  109. 109.
    Centorrino F, Price BH, Tuttle M, et al. EEG abnormalities during treatment with typical and atypical antipsychotics. Am J Psychiatry 2002 Jan; 159(1): 109–15PubMedGoogle Scholar
  110. 110.
    Freedman J, Wirshing W, Russel A, et al. Absence status seizures after successful long-term clozapine treatment of an adolescent with schizophrenia. J Child Adolesc Psychopharmacol 1994; 4: 53–62Google Scholar
  111. 111.
    Labellarte MJ, Crosson JE, Riddle MA. The relevance of prolonged QTc measurement to pediatric psychopharmacology. J Am Acad Child Adolesc Psychiatry 2003 Jun; 42(6): 642–50PubMedGoogle Scholar
  112. 112.
    DelBello MP, Versavel M, Ice K, et al. Tolerability of oral ziprasidone in children and adolescents with bipolar mania, schizophrenia, or schizoaffective disorder. J Child Adolesc Psychopharmacol 2008 Oct; 18(5): 491–9PubMedGoogle Scholar
  113. 113.
    Ronaldson KJ, Taylor AJ, Fitzgerald PB, et al. Diagnostic characteristics of clozapine-induced myocarditis identified by an analysis of 38 cases and 47 controls. J Clin Psychiatry 2010; 71(8): 982–3Google Scholar
  114. 114.
    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): 1190–6PubMedGoogle Scholar
  115. 115.
    Masi G, Perugi G, Millepiedi S, et al. Pharmacological response in juvenile bipolar disorder subtypes: a naturalistic retrospective examination. Psychiatry Res 2010 May; 177(1–2): 192–8PubMedGoogle Scholar
  116. 116.
    Asarnow JR. Childhood-onset schizotypal disorder: a follow-up study and comparison with childhood-onset schizophrenia. J Child Adolesc Psychopharmacol 2005 Jun; 15(3): 395–402PubMedGoogle Scholar
  117. 117.
    Masi G, Pfanner C, Millepiedi S, et al. Aripiprazole augmentation in 39 adolescents with treatment refractory obsessive-compulsive disorder. J Clin Psychopharmacol 2010 Dec; 30(6): 688–93PubMedGoogle Scholar
  118. 118.
    Sporn AL, Addingtron 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): 989–94PubMedGoogle Scholar
  119. 119.
    Kaufman J, Birmaher B, Breslau D, et al. Kiddie-SADS — Present and Lifetime Version (K-SADS-PL). Pittsburgh: University of Pittsburgh, School of Medicine, Oct 1996 [online]. Available from URL: http://www.wpic.pitt.edu/ksads/ksads-pl.pdf [Accessed 2010 Dec 16]
  120. 120.
    Andreasen N. The scale for the assessment of positive and negative symptoms (SAPS and SANS). Iowa City (IA): Iowa University Press, 1984Google Scholar
  121. 121.
    Kay SR, Fiszbain Opler LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261–76PubMedGoogle Scholar
  122. 122.
    Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychol Rep 1962; 10: 799–812Google Scholar
  123. 123.
    Meehl PE. Schizotaxia, schizotypy, schizophrenia. Am Psychol 1962; 17: 827–38Google Scholar
  124. 124.
    Tsuang MT, Stone WS, Faraone SV. Towards the prevention of schizophrenia. Biol Psychiatry 2000 Sep 1; 48(5): 349–56PubMedGoogle Scholar
  125. 125.
    Schultze-Lutter F, Rurhmann S, Berning J, et al. Basic symptoms and ultrahigh risk criteria: symptom development in the initial prodromal state. Schizophr Bull 2010 Jan; 36(1): 182–91PubMedCentralPubMedGoogle Scholar
  126. 126.
    McGorry PD, Nelson B, Amminger GP, et al. Intervention in individuals at ultrahigh risk for psychosis: a review and future directions. J Clin Psychiatry 2009 Sep; 70(9): 1206–12PubMedGoogle Scholar
  127. 127.
    Tsuang MT, Stone WS, Seidman LJ, et al. Treatment of non-psychotic relatives of patients with schizophrenia: four cases studies. Biol Psychiatry 1999 Jun 1; 45(11): 1412–8PubMedGoogle Scholar
  128. 128.
    Cannon TD, Huttunen MO, Dahlstrom M, et al. Antipsychotic drug treatment in the prodromal phase of schizophrenia. Am J Psychiatry 2002 Jul; 159(7): 1230–2PubMedGoogle Scholar
  129. 129.
    McGorry PD, Yung AR, Phillips LJ, et al. Randomized controlled trials of interventions designed to reduce the risk of progression to the first episode of psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry 2002 Oct; 59(10): 921–8PubMedGoogle Scholar
  130. 130.
    Koenigsberg HW, Reynolds D, Goodman M, et al. Risperidone in the treatment of schizotypal personality disorder. J Clin Psychiatry 2003 Jun; 64(6): 628–34PubMedGoogle Scholar
  131. 131.
    Woods SW, Breier A, Zipursky RB, et al. Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome. Biol Psychiatry 2003 Aug 15; 54(4): 453–64PubMedGoogle Scholar
  132. 132.
    Fusar-Poli P, Valmaggia L, McGuire P. Can antidepressants prevent psychosis? Lancet 2007 Nov 24; 370(9601): 1746–8PubMedGoogle Scholar
  133. 133.
    Amminger GP, Berger GE, Schafer MR, et al. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry 2007 Feb 15; 61(4): 551–3PubMedGoogle Scholar
  134. 134.
    Loebel AD, Lieberman JA, Alvir JM, et al. Duration of psychosis and outcome in first-episode schizophrenia. Am J Psychiatry 1992 Sep; 149(9): 1183–8PubMedGoogle Scholar
  135. 135.
    Caine ED. Clinical perspectives on atypical antipsychotics for treatment of agitation. J Clin Psychiatry 2006; 67 Suppl. 10: 22–31PubMedGoogle Scholar
  136. 136.
    Yildiz A, Sachs GS, Turgay A. Pharmacological management of agitation in emergency settings. Emerg Med J 2003 Jul; 20(4): 339–46PubMedCentralPubMedGoogle Scholar
  137. 137.
    Khan SS, Mican LM. A naturalistic evaluation of intramuscular ziprasidone versus intramuscular olanzapine for the management of acute agitation and aggression in children and adolescents. J Child Adolesc Psychopharmacol 2006 Dec; 16(6): 671–7PubMedGoogle Scholar
  138. 138.
    Englisch S, Zink M. Combined antipsychotic treatment involving clozapine and aripiprazole. Progr Neuropsychopharmacol Biol Psychiatry 2008 Aug 1; 32(6): 1386–92Google Scholar
  139. 139.
    Chang JS, Ahn YM, Park HJ, et al. Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: a 8-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2008 May; 69(5): 720–31PubMedGoogle Scholar
  140. 140.
    Evins A, Goff D. Adjunctive antidepressant drug therapies in the treatment of negative symptoms of schizophrenia. CNS Drugs 1996; 6: 130–47Google Scholar
  141. 141.
    Jockers-Scherübl MC, Bauer A, Godemann F, et al. Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study. Int Clin Psychopharmacol 2005 Jan; 20(1): 27–31PubMedGoogle Scholar
  142. 142.
    Abbasi SH, Behpournia H, Ghoreshi A, et al. The effect of mirtazapine add-on therapy to risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial. Schizophr Res 2010 Feb; 116(2–3): 101–6PubMedGoogle Scholar
  143. 143.
    Heresco-Levy U, Javitt DC, Ermilov M, et al. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry 1999 Jan; 56(1): 29–36PubMedGoogle Scholar
  144. 144.
    Tsai GE, Yang P, Chung LC, et al. D-serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry 1999 Nov; 156(11): 1822–5PubMedGoogle Scholar
  145. 145.
    Tuominen HJ, Tiihonen J, Wahlbeck K. Glutamatergic drugs for schizophrenia: a systematic review and metaanalysis. Schizophr Res 2005 Jan1; 72(2–3): 225–34PubMedGoogle Scholar
  146. 146.
    Buchanan RW, Javitt DC, Marder SR, et al. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry 2007 Oct; 164(10): 1593–602PubMedGoogle Scholar
  147. 147.
    Sanfilipo M, Wolkin A, Angrist B, et al. Amphetamine and negative symptoms of schizophrenia. Psychopharmachology (Berl) 1996 Jan; 123(2): 211–4Google Scholar
  148. 148.
    Bodkin JA, Siris SG, Bermanzohn PC, et al. Double-blind, placebo-controlled, multicenter trial of selegiline augmentation of antipsychotic medication to treat negative symptoms in outpatients with schizophrenia. Am J Psychiatry 2005 Feb; 162(2): 388–90PubMedGoogle Scholar
  149. 149.
    Levkovitz Y, Mendlovich S, Riwkes S, et al. A doubleblind, randomized study of minoclycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry 2010 Feb; 71(2): 138–49PubMedGoogle Scholar
  150. 150.
    Lerner V, Libov I, Kotler M, et al. Combination of atypical antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder. Prog Neuropsychopharmacol Biol Psychiatry 2004 Jan; 28(1): 89–98PubMedGoogle Scholar
  151. 151.
    Goodwin G, Fleischhacker W, Arango C, et al. Advantages and disadvantages of combination treatment with antipsychotics. ECNP Consensus Meeting, March 2008, Nice. Eur Neuropsychopharmacol 2009 Jul; 19(7): 520–32Google Scholar
  152. 152.
    Wolff-Menzler C, Hasan A, Malchow B, et al. Combination therapy in the treatment of schizophrenia. Pharmacopsychiatry 2010 Jun; 43(4): 122–9PubMedGoogle Scholar
  153. 153.
    Zink M, Englisch S, Meyer-Lindenbergh A. Polypharmacy in schizophrenia. Curr Opin Psychiatry 2010 Mar; 23(2): 103–11PubMedGoogle Scholar
  154. 154.
    Tondo L, Hennen J, Baldessarini RJ. Lower suicide risk with long-term lithium treatment in major affective illness: a metaanalysis. Acta Psychiatrica Scand 2001 Sep; 104(3): 163–72Google Scholar
  155. 155.
    Tiihonen J, Wahlbeck K, Kiviniemi V. The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophr Res 2009 Apr; 109(1–3): 10–4PubMedGoogle Scholar
  156. 156.
    Whitehead C, Moss S, Cardino A. Antidepressants for people with both schizophrenia and depression. Cochrane Database Syst Rev 2002; (2): CD002035Google Scholar
  157. 157.
    Knox ED, Stimmel GL. Clinical review of a long-acting, injectable formulation of risperidone. Clin Ther 2004 Dec; 26(12): 1994–2002PubMedGoogle Scholar
  158. 158.
    Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotics in patients with chronic schizophrenia. N Engl J Med 2005 Sep 22; 353(12): 1209–23PubMedGoogle Scholar
  159. 159.
    Albers LJ, Ozdemir V. Pharmacogenomic-guided rational therapeutic drug monitoring: conceptual framework and application platforms for atypical antipsychotics. Curr Med Chem 2004 Feb; 11(3): 297–312PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.IRCCS Stella Maris, Scientific Institute of Child Neurology and PsychiatryCalambrone, PisaItaly

Personalised recommendations