Drug Safety

, Volume 27, Issue 14, pp 1135–1156 | Cite as

Benefit-Risk Assessment of Atypical Antipsychotics in the Treatment of Schizophrenia and Comorbid Disorders in Children and Adolescents

  • Paz Toren
  • Sharon Ratner
  • Nathaniel Laor
  • Abraham Weizman
Review Article

Abstract

Evidence on the efficacy and safety of atypical antipsychotics in children and adolescents with schizophrenia is limited. The purpose of this review is to assess the published data on the use of atypical antipsychotics in children and adolescents with schizophrenia alone and with comorbid disorders, and to establish benefit-risk guidelines for clinicians.

Risperidone, olanzapine and clozapine were found to be effective in the treatment of aggression and mania. Risperidone, and possibly also olanzapine, may be the drugs of choice in children with comorbid tic disorders. Ziprasidone has some monoamine reuptake inhibition properties and may be administered as an augmenting agent in children and adolescents with schizophrenia and comorbid anxiety and mood disorders.

Compared with the typical antipsychotics, the atypical drugs seem to be more effective, better tolerated and lead to better patient adherence. Importantly, the atypical antipsychotics have a lower propensity to induce extrapyramidal symptoms and a potential (shown so far only in adults) to improve cognitive function and inhibit suicidal behaviour (especially clozapine). Yet, the adverse effects associated with these agents, especially weight gain, which may also have long-term effects, can lead to non-compliance in the young population. In children and adolescents receiving clozapine, olanzapine and quetiapine (but not ziprasidone, which does not have a pro-appetite effect), particularly those with obesity or a family history of diabetes mellitus, fasting blood glucose and lipid levels must be monitored frequently. Weight gain might be better controlled when the children and their parents are properly informed about this adverse effect and diet is regulated. Another major disadvantage of the atypical antipsychotics, especially risperidone, is their association with hyperprolactinaemia, which can lead to hypogonadism-induced osteoporosis, galactorrhoea, gynaecomastia, irregular menstruation and sexual dysfunction, all seen also with typical antipsychotics. Other atypical antipsychotics, namely olanzapine and ziprasidone, have been reported to be prolactin sparing in adults, but may not be completely devoid of hyperprolactinaemic effects in children and adolescents. Thus, prolactin levels should be assessed routinely in young patients treated with atypical antipsychotics. Further, children and adolescents with hyperprolactinaemia-related effects should be switched to a prolactin-sparing agent, such as quetiapine. All atypical antipsychotics may induce sedation and they are not devoid of extrapyramidal symptoms (especially risperidone). The use of typical antipsychotics has been limited to patients who are resistant to atypical antipsychotics, intolerant to their adverse effects, or require injections or depot preparations.

Further double-blind, placebo-controlled trials and long-term safety assessments are needed before definitive conclusions can be reached about the place of atypical antipsychotics in the therapeutic armamentarium of childhood-onset schizophrenia.

Notes

Acknowledgements

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.

References

  1. 1.
    Campbell M, Rapoport JL, Simpson GM. Antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry; 1999; 38: 537–45PubMedGoogle Scholar
  2. 2.
    Remschmidt H, Fleischhaker C, Hennighausen K, et al. Management of schizophrenia in children and adolescents: the role of clozapine. Paediatr Drugs 2000; 2: 253–62PubMedGoogle Scholar
  3. 3.
    Remschmidt H, Hennighausen K, Clement HW, et al. Atypical neuroleptics in child and adolescent psychiatry. Eur Child Adolesc Psychiatry 2000; 9: 9–19Google Scholar
  4. 4.
    Bryden KE, Carrey NJ, Kutcher SP. Update and recommendations for the use of antipsychotics in early onset psychoses. J Child Adolesc Psychopharmacol 2001; 11: 113–30PubMedGoogle Scholar
  5. 5.
    Stigler KA, Potenza MN, McDougle CJ. Tolerability profile of atypical antipsychotics in children and adolescents. Paediatr Drugs 2001; 3: 927–42PubMedGoogle Scholar
  6. 6.
    Baldessarini RJ, Teicher MH. Dosing of antipsychotic agents in pediatric populations. J Child Adolesc Psychopharmacol 1995; 5: 1–4Google Scholar
  7. 7.
    Armenteros JL, Mikhail AG. Do we need placebos to evaluate new drugs in children with schizophrenia? Psychopharmacology 2002; 159: 117–24PubMedGoogle Scholar
  8. 8.
    Schotte A, Janssen PF, Gommeren W, et al. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacol 1996; 124: 57–73Google Scholar
  9. 9.
    Schmidt AW, Lebel LA, Howard Jr HR, et al. Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. Eur J Pharmacol 2001; 425: 197–201PubMedGoogle Scholar
  10. 10.
    Shiloh R, Nutt D, Weizman A, editors. Atlas of psychiatric pharmacotherapy. London: Martin Dunitz Ltd, 1999Google Scholar
  11. 11.
    Armenteros JL, Whitaker AH, Welikson M, et al. Risperidone in adolescents with schizophrenia: an open pilot study. J Am Acad Child Adolesc Psychiatry 1997; 36: 694–700PubMedGoogle Scholar
  12. 12.
    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; 6: 251–7PubMedGoogle Scholar
  13. 13.
    Lykes WC, Cueva JE. Risperidone in children with schizophrenia [letter]. J Am Acad Child Adolesc Psychiatry 1996; 35: 405–6PubMedGoogle Scholar
  14. 14.
    Quintana H, Keshavan M. Case study: risperidone in children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 1995; 34: 1292–6PubMedGoogle Scholar
  15. 15.
    Simeon JG, Carrey NJ, Wiggins DM, et al. Risperidone effects in treatment-resistant adolescents: preliminary case reports. J Child Adolesc Psychopharmacol 1995; 5: 69–79Google Scholar
  16. 16.
    Cozza SJ, Edison DL. Risperidone in adolescents [letter]. J Am Acad Child Adolesc Psychiatry 1994; 33: 1211PubMedGoogle Scholar
  17. 17.
    Mandoki MW. Risperidone treatment of children and adolescents: increased risk of extrapyramidal side effects? J Child Adolesc Psychopharmacol 1995; 5: 49–67Google Scholar
  18. 18.
    Sternlicht HC, Wells SR. Risperidone in childhood schizophrenia [letter]. J Am Acad Child Adolesc Psychiatry 1995; 34: 540PubMedGoogle Scholar
  19. 19.
    Sourander A. Risperidone for treatment of childhood schizophrenia [letter]. Am J Psychiatry 1997; 154: 1476PubMedGoogle Scholar
  20. 20.
    Zuddas A, Pintor M, Cianchetti C. Risperidone for negative symptoms [letter]. J Am Acad Child Adolesc Psychiatry 1996; 35: 839–40Google Scholar
  21. 21.
    Dicker AU, Solis S. Risperidone treatment of a psychotic adolescent. Am J Psychiatry 1996; 153: 441–2PubMedGoogle Scholar
  22. 22.
    Edelman RJ. Risperidone side effects. J Am Acad Child Adolesc Psychiatry 1996; 35: 4–5Google Scholar
  23. 23.
    Dryden-Edwards RC, Reiss AL. Differential response of psychotic and obsessive symptoms to risperidone in an adolescent. J Child Adolesc Psychopharmacol 1996; 6: 139–45PubMedGoogle Scholar
  24. 24.
    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
  25. 25.
    Zalsman G, Carmon E, Martin A, et al. Effectiveness, safety and tolerability of risperidone in adolescents with schizophrenia: an open-label study. J Child Adolesc Psychopharmacol 2003; 13: 319–27PubMedGoogle Scholar
  26. 26.
    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. Neuropsychopharmacol 2004; 29: 133–45Google Scholar
  27. 27.
    Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002; 347: 314–21Google Scholar
  28. 28.
    Findling RL, McNamara NK, Branicky LA, et al. A double-blind pilot study of risperidone in the treatment of conduct disorder. J Am Acad Child Adolesc Psychiatry 2000; 39: 509–16PubMedGoogle Scholar
  29. 29.
    Buitelaar JK, Van der Gaag RJ, Cohen-Kettenis P, et al. A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities. J Clin Psychiatry 2001; 62: 239–48PubMedGoogle Scholar
  30. 30.
    Van Bellinghen MV, De Troch C. Risperidone in the treatment of behavioral disturbances in children and adolescents with borderline intellectual functioning: a double-blind, placebo-controlled pilot study. J Child Adolesc Psychopharmacol 2001; 11: 5–13PubMedGoogle Scholar
  31. 31.
    Aman MG, Smedt SD, Derivan A, et al. Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence. Am J Psychiatry 2002; 158: 1337–46Google Scholar
  32. 32.
    Schreier HA. Risperidone for young children with mood disorder and aggressive behavior. J Child Adolesc Psychopharmacol 1998; 8: 49–59PubMedGoogle Scholar
  33. 33.
    Frazier JA, Meyer M, Biederman J, et al. Risperidone treatment for juvenile bipolar disorder: a retrospective chart review. J Am Acad Child Adolesc Psychiatry 1999; 38: 960–5PubMedGoogle Scholar
  34. 34.
    Simeon J, Milin R, Walker S. A retrospective chart review of risperidone use in treatment-resistant children and adolescents with psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 267–75PubMedGoogle Scholar
  35. 35.
    Fras I, Major LF. Clinical experience with risperidone [letter]. J Am Acad Child Adolesc Psychiatry 1995; 34: 833PubMedGoogle Scholar
  36. 36.
    Ravizza L, Barzega G, Bellino S, et al. Therapeutic effect and safety of adjunctive risperidone in refractory obsessive-compulsive disorder (OCD). Psychopharmacol Bull 1996; 32: 677–82PubMedGoogle Scholar
  37. 37.
    Andrade C. Risperidone may worsen fluoxetine-treated OCD. J Clin Psychiatry 1998; 59: 255–6PubMedGoogle Scholar
  38. 38.
    Fitzgerald KD, Stewart CM, Tawile V, et al. Risperidone augmentation of serotonin reuptake inhibitor treatment of pediatric obsessive compulsive disorder. J Child Adolesc Psychopharmacol 1999; 9: 115–23PubMedGoogle Scholar
  39. 39.
    Hanna GL, Fluent TE, Fischer DJ. Separation anxiety in children and adolescents treated with risperidone. J Child Adolesc Psychopharmacol 1999; 9: 277–83PubMedGoogle Scholar
  40. 40.
    Toren P, Laor N, Weizman A. Use of atypical neuroleptics in child and adolescent psychiatry. J Clin Psychiatry 1998; 59: 644–56PubMedGoogle Scholar
  41. 41.
    Malone RC, Maislin G, Choudhury MS, et al. Risperidone treatment in children and adolescents with autism: short- and long- term safety and effectiveness. J Am Acad Child Adolesc Psychiatry 2002; 41: 140–7PubMedGoogle Scholar
  42. 42.
    McDougle CJ, Holmes JP, Bronson MR, et al. Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective, open-label study. J Am Acad Child Adolesc Psychiatry 1997; 36: 685–93PubMedGoogle Scholar
  43. 43.
    Kelly DL, Conley RR, Love RC, et al. Weight gain in adolescents treated with risperidone and conventional antipsychotics over six months. J Child Adolesc Psychopharmacol 1998; 8: 151–9PubMedGoogle Scholar
  44. 44.
    Martin A, Landau J, Lebens P, et al. Risperidone-associated weight gain in children and adolescents: a retrospective chart review. J Child Adolesc Psychopharmacol 2000; 10: 259–68PubMedGoogle Scholar
  45. 45.
    Hellings JA, Zarcone JR, Crandall K, et al. Weight gain in a controlled study of risperidone in children, adolescents and adults with mental retardation and autism. J Child Adolesc Psychopharmacol 2001; 11: 229–38PubMedGoogle Scholar
  46. 46.
    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; 41: 337–43PubMedGoogle Scholar
  47. 47.
    Saito E, Kafantaris V. Can diabetes mellitus be induced by medication? J Child Adolesc Psychopharmacol 2002; 12: 231–6PubMedGoogle Scholar
  48. 48.
    Martin A, L’Ecuyer S. Triglyceride, cholesterol and weight changes among risperidone-treated youths: a retrospective study. Eur Child Adolesc Psychiatry 2002; 11: 129–33PubMedGoogle Scholar
  49. 49.
    Conner DF, Fletcher KE, Wood JS. Neuroleptic-related dyskinesias in children and adolescents. J Clin Psychiatry 2001; 62: 967–74Google Scholar
  50. 50.
    Feeney DJ, Klykylo W. Risperidone and tardive dyskinesia. J Am Acad Child Adolescent Psychiatry 1996; 35: 1421–2Google Scholar
  51. 51.
    Rowan AB, Malone RP. Tics with risperidone withdrawal. J Am Acad Child Adolesc Psychiatry 1997; 36: 162–3PubMedGoogle Scholar
  52. 52.
    Cohen LG, Biederman J. Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children. J Am Acad Child Adolesc Psychiatry 2001; 11: 435–40Google Scholar
  53. 53.
    Gupta S, Frank B, Madhusoodanan S. Risperidone-associated galactorrhea in a male teenager [letter]. J Am Acad Child Adolesc Psychiatry 2001; 40: 504–5PubMedGoogle Scholar
  54. 54.
    Masi G, Cosenza A, Mucci M. Prolactin levels in young children with pervasive developmental disorders during risperidone treatment. J Child Adolesc Psychopharmacol 2001; 11: 389–94PubMedGoogle Scholar
  55. 55.
    Kumra S, Herion D, Jacobsen LK, et al. Case study: risperidone-induced hepatotoxicity in pediatric patients. J Am Acad Child Adolesc Psychiatry 1997; 36: 701–5PubMedGoogle Scholar
  56. 56.
    Landau J, Martin A. Is liver function monitoring warranted during risperidone treatment? J Am Acad Child Adolesc Psychiatry 1998; 37: 1007–8PubMedGoogle Scholar
  57. 57.
    Szighety E, Wiznitzer M, Brancky LA, et al. Risperidone-induced hepatotoxicity in children and adolescents?: a chart review. J Child Adolesc Psychopharmacol 1999; 9: 93–8Google Scholar
  58. 58.
    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. 1994; Washington, DC: American Psychiatric AssociationGoogle Scholar
  59. 59.
    Margolese HC, Lawrence A, Yves D. Depression and dysphoria in adult and adolescent patients with Tourette’s disorder treated with risperidone. J Clin Psychiatry 2002; 63: 1040–4PubMedGoogle Scholar
  60. 60.
    Marder SR, Meibach RC. Risperidone in the treatment of schizophrenia. Am J Psychiatry 1994; 151: 825–35PubMedGoogle Scholar
  61. 61.
    Robb AS, Chang W, Lee HK, et al. Risperidone-induced neuroleptic malignant syndrome in an adolescent. J Child Adolesc Psychopharmacol 2000; 10: 327–30PubMedGoogle Scholar
  62. 62.
    Sharma R, Trappler B, Ng YK, et al. Risperidone-induced neuroleptic malignant syndrome. Am Pharmacother 1996; 30: 775–8Google Scholar
  63. 63.
    Took KJ, Buck BL. Enuresis with combined risperidone and SSRI use. J Am Acad Child Adolesc Psychiatry 1996; 35: 840–1PubMedGoogle Scholar
  64. 64.
    Posey DJ, Walsh KH, Wilson GA, et al. Risperidone in the treatment of two very young children with autism. J Child Adolesc Psychopharmacol 1999; 9: 273–6PubMedGoogle Scholar
  65. 65.
    Krishnamoorthy J, King BH. Open label olanzapine treatment in five preadolescent children. J Child Adolesc Psychopharmacol 1998; 8(2): 107–13PubMedGoogle Scholar
  66. 66.
    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; 37(4): 377–85PubMedGoogle Scholar
  67. 67.
    Maagensen M, Aarkrog T. Treatment of adolescent psychosis with olanzapine. Nordic J Psychiatry 1999; 53: 435–8Google Scholar
  68. 68.
    Sholevar EH, Baron DA, Hardie TL. Treatment of childhood-onset schizophrenia with olanzapine. J Child Adolesc Psychopharmacol 2000; 10(2): 69–78PubMedGoogle Scholar
  69. 69.
    Findling RL, McNamara NK, Youngstrom EA, et al. A prospective, open-label trial of olanzapine in adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 2003; 42: 170–5PubMedGoogle Scholar
  70. 70.
    Haapasalo-Pesu KM, Saarijarvi S. Olanzapine induces remarkable weight gain in adolescent patients: case report. Eur Child Adolesc Psychiatry 2001; 10(3): 205–8PubMedGoogle Scholar
  71. 71.
    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; 13: 301–9PubMedGoogle Scholar
  72. 72.
    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; 13: 311–7PubMedGoogle Scholar
  73. 73.
    Ercan ES, Kutlu A, Varon A, et al. Olanzapine treatment of eight adolescent patients with psychosis. Hum Psychopharmacol 2004; 19: 53–6PubMedGoogle Scholar
  74. 74.
    Frazier JA, Biederman J, Tohen M, et al. A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder. J Child Adolesc Psychopharmacol 2001; 11: 239–50PubMedGoogle Scholar
  75. 75.
    Soutullo CA, Sorter MT, Foster KD, et al. Olanzapine in the treatment of adolescent acute mania: a report of seven cases. J Affect Disord 1999; 53: 279–83PubMedGoogle Scholar
  76. 76.
    Chang KD, Ketter TA. Mood stabilizer augmentation with olanzapine in acutely manic children. Child Adolesc Psychopharmacol 2000; 10: 45–9Google Scholar
  77. 77.
    Khouzam HR, El-Gabalawi F. Treatment of bipolar I disorder in an adolescent with olanzapine. J Child Adolesc Psychopharmacol 2000; 10: 147–51PubMedGoogle Scholar
  78. 78.
    Potenza MN, Holmes JP, Kanes SJ, et al. Olanzapine treatment of children, adolescents, and adults with pervasive developmental disorders: an open-label pilot study. J Clin Psychopharmacol 1999; 19: 37–44PubMedGoogle Scholar
  79. 79.
    Schur SB, Sikich L, Findling RL, et al. Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY). Part I: a review. J Am Acad Child Adolesc Psychiatry 2003; 42: 132–44PubMedGoogle Scholar
  80. 80.
    Sheikh RM, Ahmed K. The efficacy of olanzapine, as needed, to treat acute agitation in juveniles. J Child Adolesc Psychopharmacol 2002; 12: 71–3PubMedGoogle Scholar
  81. 81.
    Mehler C, Wetzer CH, Schulze U, et al. Olanzapine in children and adolescents with chronic anorexia nervosa: a study of 5 cases. Eur Child Adolesc Psychiatry 2001; 10: 151–7PubMedGoogle Scholar
  82. 82.
    Francobandiera G. Olanzapine augmentation of serotonin uptake inhibitors in obsessive compulsive disorder: an open study. Can J Psychiatry 2001; 46: 356–8PubMedGoogle Scholar
  83. 83.
    De Haan L, Beuk N, Hoogenboom B, et al. Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders. J Clin Psychiatry 2002; 63: 104–7PubMedGoogle Scholar
  84. 84.
    Gothelf D, Falk B, Singer P, et al. Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophrenic inpatients treated with olanzapine. Am J Psychiatry 2002; 159: 1055–957PubMedGoogle Scholar
  85. 85.
    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; 35: 339–45PubMedGoogle Scholar
  86. 86.
    Domon SE, Webber JC. Case report: hyperglycemia and hypertriglyceridemia secondary to olanzapine. J Child Adolesc Psychopharmacol 2001; 11: 285–8PubMedGoogle Scholar
  87. 87.
    Selva KA, Scott SM. Diabetic ketoacidosis associated with olanzapine in an adolescent patient. J Pediatr 2001; 138: 936–8PubMedGoogle Scholar
  88. 88.
    Poyurovsky M, Isaacs I, Fuchs C, et al. Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study. Am J Psychiatry 2003; 160: 297–302PubMedGoogle Scholar
  89. 89.
    Morrison JA, Cottingham EM, Barton BA. Metformin for weight loss in pediatric patients taking psychotropic drugs. Am J Psychiatry 2002; 159: 655–7PubMedGoogle Scholar
  90. 90.
    Goldstein LE, Sporn J, Brown S, et al. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics 1999; 40: 438–43PubMedGoogle Scholar
  91. 91.
    Nguyen M, Murphy T. Olanzapine and hypertriglyceridemia [letter]. J Am Acad Child Adolesc Psychiatry 2001; 40: 133PubMedGoogle Scholar
  92. 92.
    Beasley C, Tollefson G, Tran P. Safety of olanzapine. J Clin Psychiatry 1997; 58: 13–7PubMedGoogle Scholar
  93. 93.
    Tollefson GD, Beasley Jr CM, Tamura RN, et al. Blind, controlled, long-term study of comparative incidence of treatment-emergent tardive dyskinesia with olanzapine or haloperidol. Am J Psychiatry 1997; 154: 1248–54PubMedGoogle Scholar
  94. 94.
    Agarwal V, Kumar P. Olanzapine in the treatment of tardive dyskinesia: a report of 2 cases. J Clin Psychiatry 2001; 64: 298–9Google Scholar
  95. 95.
    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; 37: 221–7PubMedGoogle Scholar
  96. 96.
    Woods SW, Martin A, Spector SG, et al. Effects of development on olanzapine-associated adverse events. J Am Acad Child Adolesc Psychiatry 2002; 41: 1439–45PubMedGoogle Scholar
  97. 97.
    Crawford AM, Beasley Jr CM, Tollefson GD. The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations. Schizophr Res 1997; 26: 41–54PubMedGoogle Scholar
  98. 98.
    Alfaro CL, Wudarsky M, Nicolson R, et al. Correlation of antipsychotic and prolactin concentration in children and adolescents acutely treated with haloperidol, clozapine, or olanzapine. J Child Adolesc Psychopharmacol 2002; 12: 83–91PubMedGoogle Scholar
  99. 99.
    Aubry JM, Simon AE, Bertschy G. Possible induction of mania and hypomania by olanzapine or risperidone: a critical review of reported cases. J Clin Psychiatry 2000; 61: 649–55PubMedGoogle Scholar
  100. 100.
    London JA. Mania associated with olanzapine. J Am Acad Child Adolesc Psychiatry 1998; 37: 135–6PubMedGoogle Scholar
  101. 101.
    Philibert RA, Adam LA, Frank FM, et al. Olanzapine usage associated with neuroleptic malignant syndrome. Pyschosomatics 2001; 42: 528–9Google Scholar
  102. 102.
    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; 98: 63–5PubMedGoogle Scholar
  103. 103.
    Beasley C, Sanger T, Satterlee W, et al. Olanzapine versus placebo: results of a double-blind, fixed-dose olanzapine trial. Psychopharmacology 1996; 124: 159–67PubMedGoogle Scholar
  104. 104.
    Kumra S, Frazier JA, Jacobsen LK, et al. Childhood-onset schizophrenia: a double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry 1996; 53: 1090–7PubMedGoogle Scholar
  105. 105.
    Schultz E, Fleischhaker C, Clement HW, et al. Blood biobenic amines during clozapine treatment of early-onset schizophrenia. J Neural Transm 1999; 104: 1077–89Google Scholar
  106. 106.
    Siefen G, Remschmidt H. Results of treatment with clozapine in schizophrenic adolescents. Z Kinder Jugenpsychiatr 1986; 14: 245–7PubMedGoogle Scholar
  107. 107.
    Birmaher B, Baker R, Kapur S, et al. Clozapine for the treatment of adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 1992; 31: 160–4PubMedGoogle Scholar
  108. 108.
    Boxer G, Davidson J. More on clozapine [letter]. J Am Acad Child Adolesc Psychiatry 1992; 31: 993PubMedGoogle Scholar
  109. 109.
    Mandoki M. Clozapine for adolescents with psychosis: literature review and 2 case reports. J Child Adolesc Psychopharmacol 1993; 3: 213–21Google Scholar
  110. 110.
    Blanz B, Schmidt MH. Clozapine for schizophrenia [letter]. J Am Acad Child Adolesc Psychiatry 1993; 32: 223–4PubMedGoogle Scholar
  111. 111.
    Mozes T, Toren P, Chernauzan N, et al. Clozapine treatment in very early onset schizophrenia. J Am Acad Child Adolesc Psychiatry 1994; 33: 65–70PubMedGoogle Scholar
  112. 112.
    Jacobsen LK, Walker MC, Edwards JE, et al. Clozapine in the treatment of a young adolescent with schizophrenia. J Am Acad Child Adolesc Psychiatry 1994; 33: 645–50PubMedGoogle Scholar
  113. 113.
    Towbin KE, Dykens EM, Pugliese RG. Clozapine for early developmental delays with childhood-onset schizophrenia: protocol and 15 months outcome. J Am Acad Child Adolesc Psychiatry 1994; 33: 651–7PubMedGoogle Scholar
  114. 114.
    Freedman JE, Wirshing WC, Russell AT, et al. Absence status seizures during successful long-term clozapine treatment of an adolescent with schizophrenia. J Child Adolesc Psychopharmacol 1994; 4: 53–62Google Scholar
  115. 115.
    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; 33: 658–63PubMedGoogle Scholar
  116. 116.
    Gordon CT, Frazier JA, McKenna K, et al. Childhood-onset schizophrenia: an NIMH study in progress. Schizophr Bull 1994; 20: 697–712PubMedGoogle Scholar
  117. 117.
    Remschmidt H, Schulz E, Martin M. An open trial of clozapine in thirty-six adolescents with schizophrenia. J Child Adolesc Psychgopharmacol 1994; 4: 31–41Google Scholar
  118. 118.
    Levkovitch Y, Kaysar N, Kronnemberg Y, et al. Clozapine for schizophrenia [letter]. J Am Acad Child Adolesc Psychiatry 1994; 33: 431PubMedGoogle Scholar
  119. 119.
    Piscitelli SC, Frazier JA, McKenna K, et al. Plasma clozapine and haloperidol concentrations in adolescents with childhood-onset schizophrenia: association with response. J Clin Psychiatry 1994; 55: 94–7PubMedGoogle Scholar
  120. 120.
    Abezynska M, Karmirek Z, Syguda J, et al. Own experience (1989-1994) in the treatment of adolescent schizophrenic paranoid syndromes with Leponex produced by Sandoz Company. Psychiatr Pol 1995; 29: 79–85Google Scholar
  121. 121.
    Schulz B, Fleischhaker C, Remschmidt HE. Correlated changes in symptoms and neurotransmitter indices during maintenance treatment with clozapine or conventional neuroleptics in adolescents and young adults with schizophrenia. J Child Adolesc Psychopharmacol 1996; 6: 119–31PubMedGoogle Scholar
  122. 122.
    Burke MS, Josephson A, Sebastian CS, et al. Clozapine and cognitive function [letter]. J Am Acad Child Adolesc Psychiatry 1995; 34: 127–8PubMedGoogle Scholar
  123. 123.
    Levkovitch Y, Kronenberg J, Kayser N, et al. Clozapine for tardive dyskinesia in adolescents. Brain Dev 1995; 17: 213–5PubMedGoogle Scholar
  124. 124.
    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: 241–53Google Scholar
  125. 125.
    MacEwan TH, Morton MJS. Use of clozapine in a child with treatment- resistant schizophrenia. Br J Psychiatry 1996; 168: 376–8PubMedGoogle Scholar
  126. 126.
    Turpeinen P. Clozapine in adolescent psychiatric patients [letter]. CNS Drugs 1996; 6: 339–40Google Scholar
  127. 127.
    Turetz M, Mozes T, Toren P, et al. Clozapine treatment in childhood-onset schizophrenia. Br J Psychiatry 1997; 170: 507–10PubMedGoogle Scholar
  128. 128.
    Chalasani L, Kant R, Chengappa KNR. Clozapine impact on clinical outcome and aggression in severely ill adolescents with childhood-onset schizophrenia. Can J Psychiatry 2001; 46: 965–72PubMedGoogle Scholar
  129. 129.
    Chen NC, Bedair HS, McKay B, et al. Clozapine in the treatment of aggression in an adolescent with autistic disorder. J Clin Psychiatry 2001; 62: 479–80PubMedGoogle Scholar
  130. 130.
    Fuchs DC. Clozapine treatment of bipolar disorder in a young adolescent. J Am Acad Child Adolesc Psychiatry 1994; 33: 1299–302PubMedGoogle Scholar
  131. 131.
    Masi G, Milone A. Clozapine treatment in adolescent with bipolar disorder. Panminerva Med 1998; 40: 254–7PubMedGoogle Scholar
  132. 132.
    Patel B, Tandon R. Development of obsessive compulsive symptoms during clozapine treatment [letter]. Am J Psychiatry 1993; 150: 836PubMedGoogle Scholar
  133. 133.
    Reitzle K, Warnke A, Wewtzer C, et al. Agranulocytosis in child with schizophrenia treated with clozapine-clinical finding and therapy, a case report. Z Kinder Jugendpsychiatr Psychother 2001; 29: 137–43PubMedGoogle Scholar
  134. 134.
    Findling RL, McNamara NK, Gracious BL. Paediatric uses of atypical antipsychotics. Exp Opin Pharmacother 2000; 1: 935–45Google Scholar
  135. 135.
    Spivak B, Adersberg S, Rosen L, et al. Trihexyphenidyl treatment of clozapine-induced hypersalivation. Int Clin Psychopharmacol 1997; 12: 213–5PubMedGoogle Scholar
  136. 136.
    Remschmidt H, Schulz E, Herpertz-Dahlmann B. Schizophrenia psychoses in childhood and adolescence: a guide to diagnosis and drug choice. CNS Drugs 1996; 6: 100–12Google Scholar
  137. 137.
    Meltzer HY, Luchins DJ. Effect of clozapine in severe tardive dyskinesia: a case report. J Clin Psychopharmacol 1984; 4: 286–7PubMedGoogle Scholar
  138. 138.
    Frankenburg FR, Kando J. Eosinophilia, clozapine, and pancreatitis [letter]. Lancet 1992; 340: 251PubMedGoogle Scholar
  139. 139.
    Koller E, Malozowski S, Doraiswamy PM. Atypical antipsychotic drugs and hyperglycemia in adolescents [letter]. JAMA 2001; 286: 2547–8PubMedGoogle Scholar
  140. 140.
    Brown MB. Clozapine, neuroleptic malignant syndrome, and pancerebellar syndrome. Psychsomatics 1999; 40: 518–20Google Scholar
  141. 141.
    Lund BC, Perry PJ, Brooks JM, et al. Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach. Arch Gen Psychiatry 2001; 58: 1172–6PubMedGoogle Scholar
  142. 142.
    Gaulin BD, Markowitz JS, Caley CF, et al. Clozapine-associated elevation in serum triglycerides. Am J Psychiatry 1999; 156: 1270–2PubMedGoogle Scholar
  143. 143.
    McConville B, Arvanitis L, Thyrum P, et al. Pharmacokinetics, tolerability and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders. J Clin Psychiatry 2000; 61: 252–60PubMedGoogle Scholar
  144. 144.
    Shaw JA, Lewis JE, Pascal S, et al. A study of quetiapine: efficacy and tolerability in psychotic adolescents. J Child Adolesc Psychopharmacol 2001; 11: 415–24PubMedGoogle Scholar
  145. 145.
    Szighety E, Brent S, Findling R. Quetiapine for refractory schizophrenia. J Am Acad Child Adolesc Psychiatry 1998; 37: 1127–8Google Scholar
  146. 146.
    Healy E, Subotsky F, Pipe R. Quetiapine in adolescent psychosis [letter]. J Am Acad Child Adolesc Psychiatry 1999; 38: 1329PubMedGoogle Scholar
  147. 147.
    Hayden F. Long-term remission of schizophrenia in an adolescent treated with quetiapine. J Child Adolesc Psychopharmacol 2001; 11: 289–93PubMedGoogle Scholar
  148. 148.
    Bardenstein L, Kurashov A, Mozhginski Y, et al. Aggressive behavior in adolescents: an open-label study with quetiapine [poster no. 145]. Eur Psychiatry 2002, 118SGoogle Scholar
  149. 149.
    DelBello MP, Schwiers ML, Rosenberg HL, et al. A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry 2002; 41: 1216–23PubMedGoogle Scholar
  150. 150.
    Schaller JL, Behar D. Quetiapine for refractory mania in a child. J Am Acad Child Adolesc Psychiatry 1999; 38: 498–9PubMedGoogle Scholar
  151. 151.
    Martin A, Koenig K, Scahill L, et al. Open-label quetiapine in the treatment of children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol 1999; 9: 99–107PubMedGoogle Scholar
  152. 152.
    Domon SE, Cargile CS. Quetiapine-associated hyperglycemia and hypertriglyceridemia. J Am Acad Child Adolesc Psychiatry 2002; 41: 495–6PubMedGoogle Scholar
  153. 153.
    Buckly PF. Ziprasidone: pharmacology, clinical progress and therapeutic promise. Drugs Today 2000; 36: 583–90Google Scholar
  154. 154.
    Weizman R, Weizman A. Use of atypical antipsychotics in mood disorders. Curr Opin Investig Drugs 2001; 2: 940–5PubMedGoogle Scholar
  155. 155.
    Keck Jr PE, Strakowski SM, McElroy SL. The efficacy of atypical antipsychotics in the treatment of depressive symptoms, hostility in patients with schizophrenia. J Clin Psychiatry 2000; 3: 4–9Google Scholar
  156. 156.
    Patel NC, Sierk P, Dorson PG, et al. Experience with ziprasidone [letter]. J Am Acad Child Adolesc Psychiatry 2002; 41: 495PubMedGoogle Scholar
  157. 157.
    McDougle CJ, Kem DL, Posey DJ. Case series: use of ziprasidone for maladaptive symptoms in youths with autism. J Am Acad Child Adolesc Psychiatry 2002; 41: 921–7PubMedGoogle Scholar
  158. 158.
    Sallee FR, Kurlan R, Goetz CG, et al. Ziprasidone treatment of children and adolescents with Tourette’s syndrome: a pilot study. J Am Acad Child Adolesc Psychiatry 2000; 39: 292–9PubMedGoogle Scholar
  159. 159.
    Labellarte MG, Crosson JE, Riddle MA. The relevance of prolonged QTc measurement to pediatric psychopharmacology. J Am Acad Child Adolesc Psychiatry 2003; 42: 642–50PubMedGoogle Scholar
  160. 160.
    Jordan MP. Ziprasidone-associated galactorrea in a female teenager. J Am Acad Child Adolesc Psychiatry 2003; 42: 4–5PubMedGoogle Scholar
  161. 161.
    Keck Jr PE, McElroy SL. Aripiprazole: a partial dopamine agonist D2 receptor agonist antipsychotic. Expert Opin Investig Drugs 2003; 12: 655–62PubMedGoogle Scholar
  162. 162.
    Staller JA. Aripiprazole in an adult with Asperger disorder. Ann Pharmacother 2003; 37: 1628–1631PubMedGoogle Scholar
  163. 163.
    Lindsey RL, Kaplan D, Koliatsos V. Aripiprazole and extrapyramidal symptoms. J Am Acad Child Adolesc Psychiatry 2003; 42: 1268–9PubMedGoogle Scholar
  164. 164.
    Paillere-Martinot ML, Lecrubier Y, Martinot JL, et al. Improvement of some schizophrenic deficit symptoms with low doses of amisulpiride. Am J Psychiatry 1995; 152: 130–3PubMedGoogle Scholar
  165. 165.
    Pool D, Bloom W, Mielke DH, et al. A controlled evaluation of loxitane in seventy-five adolescent schizophrenic patients. Curr Ther Res 1976; 19: 99–104PubMedGoogle Scholar
  166. 166.
    Pangalila-Ratulangi EA. Pilot evaluation of Orap (pimozide) in child psychiatry. Psychiatr Neurol Neurochir 1973; 76: 17–27PubMedGoogle Scholar
  167. 167.
    Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003; 60: 82–91PubMedGoogle Scholar
  168. 168.
    Spencer EK, Kafantaris V, Padron-Gayol MV, et al. Haloperidol in schizophrenic children: early findings from a study in progress. Psychopharmacol Bull 1992; 28: 183–6PubMedGoogle Scholar
  169. 169.
    Bengi Semerci Z. Olanzapine in Tourette’s disorder [letter]. J Am Acad Child Adolesc Psychiatry 2000; 39: 140PubMedGoogle Scholar
  170. 170.
    Valiquette G. Risperidone in children and adolescents with autism and serious behavioral problems. N Engl J Med 2002; 347: 1890–1PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Paz Toren
    • 1
  • Sharon Ratner
    • 1
  • Nathaniel Laor
    • 1
    • 2
  • Abraham Weizman
    • 3
    • 4
  1. 1.Tel Aviv-Brull Community Mental Health Center and Sackler Faculty of MedicineTel Aviv UniversityTel-AvivIsrael
  2. 2.Yale Child Study CenterNew HavenUSA
  3. 3.Geha Mental Health Center and Felsenstein Medical Research CenterPetah TiqwaIsrael
  4. 4.Sackler Faculty of Medicine, Tel Aviv UniversityTel-AvivIsrael

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