Skip to main content
Log in

Pharmacotherapy of Pervasive Developmental Disorders in Children and Adolescents

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

Abstract

Pervasive developmental disorders (PDDs) are severe psychiatric disorders characterised by impaired social interaction, reduced verbal and nonverbal communication, and restricted and stereotyped patterns of interest and behaviour, with onset in the first 3 years of life. As part of a multimodal approach that includes educational and behavioural interventions, appropriate use of pharmacotherapy in patients with PDDs can improve some symptoms and behaviours and increase the patient’s response to nonpharmacological interventions. Pharmacotherapy is aimed at stabilising the dysregulated systems that are thought to underlie the abnormal behaviours, namely the serotonergic and dopaminergic systems.

This paper critically reviews the available literature on the pharmacotherapy of PDDs in children and adolescents. Pharmacological, efficacy and safety data on drugs acting on serotonin (serotonergic agents such as clomipramine, fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine), on both serotonin and norepinephrine (venlafaxine and mirtazapine), dopamine (dopamine-blocking antipsychotics such as haloperidol and pimozide), and on both serotonin and dopamine (atypical antipsychotics such as clozapine, risperidone, olanzapine, quetiapine and ziprasidone) are presented. The paper concludes with a brief discussion of other psychotropic medications, such as the opioid antagonists, α-adrenoceptor agonists (clonidine and guanfacine), psychostimulants, mood stabilisers, glutamatergic compounds (lamotrigine, amantadine), buspirone, and secretin. Available evidence suggests that atypical antipsychotics (mainly risperidone and olanzapine) are particularly indicated when more serious behavioural symptoms, such as aggression, self-injurious behaviours and hyperactivity, are prominent. Serotonergic agents may be effective in children with repetitive phenomena or affective symptoms. Social relatedness is more frequently refractory to both atypical antipsychotics and serotonergic agents.

Further research into the drug treatment of PDDs, including placebo-controlled trials and long-term, naturalistic follow-up studies of large samples of patients of different age ranges, is warranted.

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.

Institutional subscriptions

Table I
Table II
Table III
Table IV

Similar content being viewed by others

References

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

    Google Scholar 

  2. Anderson GM, Hoshino Y. Neurochemical studies of autism. In: Cohen DJ, Volkmar FR, editors. Handbook of autism and pervasive developmental disorders. New York: John Wiley & Sons, 1997: 325–43

    Google Scholar 

  3. Anderson GM, Freedman DX, Cohen DJ, et al. Whole blood serotonin in autistic and normal subjects. J Child Psychol Psychiatry 1987 Nov; 28(6): 885–900

    Article  PubMed  CAS  Google Scholar 

  4. Cook Jr EH, Leventhal BL, Heller W, et al. Autistic children and their relatives: relationships between serotonin and norepinephrine levels and intelligence. J Neuropsychiatry Clin Neurosci 1990 Summer; 2(3): 268–74

    PubMed  Google Scholar 

  5. Minderaa RB, Anderson GM, Volkmar FR, et al. Whole blood serotonin and tryptophan in autism: temporal stability and the effects of medication. J Autism Dev Disord 1989 Mar; 19(1): 129–36

    Article  PubMed  CAS  Google Scholar 

  6. Cook Jr EH, Leventhal BL. The serotonin system in autism. Curr Opin Pediatr 1996 Aug; 8(4): 348–54

    Article  PubMed  CAS  Google Scholar 

  7. McBride PA, Anderson GM, Hertzig ME, et al. Effects of diagnosis, race, and puberty on platelet serotonin levels in autism and mental retardation. J Am Acad Child Adolesc Psychiatry 1998 Jul; 37(7): 767–76

    Article  PubMed  CAS  Google Scholar 

  8. Partington MW, Tu JB, Wong CY. Blood serotonin levels in severe mental retardation. Dev Med Child Neurol 1973 Oct; 15(5): 616–27

    Article  PubMed  CAS  Google Scholar 

  9. Todd RD, Ciaranello RD. Demonstration of inter- and intraspecies differences in serotonin binding sites by antibodies from an autistic child. Proc Natl Acad Sci U S A 1985 Jan; 82(2): 612–6

    Article  PubMed  CAS  Google Scholar 

  10. Yuwiler A, Shih JC, Chen CH, et al. Hyperserotoninemia and antiserotonin antibodies in autism and other disorders. J Autism Dev Disord 1992 Mar; 22(1): 33–45

    Article  PubMed  CAS  Google Scholar 

  11. Cook Jr EH, Perry BD, Dawson G, et al. Receptor inhibition by immunoglobulins: specific inhibition by autistic children, their relatives, and control subjects. J Autism Dev Disord 1993 Mar; 23(1): 67–78

    Article  PubMed  Google Scholar 

  12. Hoshino Y, Yamamoto T, Kanelo M, et al. Blood serotonin and free tryptophan concentration in autistic children. Neuropsychobiology 1984; 11(1): 22–7

    Article  PubMed  CAS  Google Scholar 

  13. McBride PA, Anderson GM, Hertzig ME, et al. Serotonergic responsivity in male young adults with autistic disorder: results of a pilot study. Arch Gen Psychiatry 1989 Mar; 46(3): 213–21

    Article  PubMed  CAS  Google Scholar 

  14. McDougle CJ, Naylor ST, Cohen DJ, et al. Effects of tryptophan depletion in drug-free adults with autistic disorder. Arch Gen Psychiatry 1996 Nov; 53(11): 993–1000

    Article  PubMed  CAS  Google Scholar 

  15. Leonard HL, March J, Rickler KC, et al. Pharmacology of the selective serotonin reuptake inhibitors in children and adolescents. J Am Acad Child Adolesc Psychiatry 1997 Jun; 36(6): 725–36

    Article  PubMed  CAS  Google Scholar 

  16. Geller DA, Hoog SL, Heiligenstein JH, et al. Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial. J Am Acad Child Adolesc Psychiatry 2001 Jul; 40(7): 773–9

    Article  PubMed  CAS  Google Scholar 

  17. March JS, Biederman J, Wolchow R, et al. Sertraline in children and adolescents with obsessive-compulsive disorder: a multi-center randomized controlled trial. J Am Med Assn 1998 Nov; 280(20): 1752–6

    Article  CAS  Google Scholar 

  18. Riddle MA, Reeve EA, Yaryura-Tobias JA, et al. Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled multicenter trial. J Am Acad Child Adolesc Psychiatry 2001; 40(2): 222–9

    Article  PubMed  CAS  Google Scholar 

  19. McDougle CJ, Kresch LE, Goodman WK, et al. A case-controlled study of repetitive thoughts and behavior in adults with autistic disorder and obsessive-compulsive disorder. Am J Psychiatry 1995 May; 152(5): 772–7

    PubMed  CAS  Google Scholar 

  20. Gordon CT, State RC, Nelson JE, et al. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch Gen Psychiatry 1993 Jun; 50(6): 441–7

    Article  PubMed  CAS  Google Scholar 

  21. Cook EH, Rowlett R, Jaselskis C, et al. Fluoxetine treatment of children and adults with autistic disorder and mental retardation. J Am Acad Child Adolesc Psychiatry 1992 Jul; 31(4): 739–45

    Article  PubMed  Google Scholar 

  22. DeLong GR, Ritch CR, Burch S. Fluoxetine response in children with autistic spectrum disorder: correlation with familial major affective disorder and intellectual achievement. Dev Med Child Neurol 2002 Oct; 44(10): 652–9

    Article  PubMed  Google Scholar 

  23. Steingard RJ, Zimnitzky B, De Maso DR, et al. Sertraline treatment of transition-associated anxiety and agitation in children with autistic disorder. J Child Adolesc Psychopharmacol 1997 Spring; 7(1): 9–15

    Article  PubMed  CAS  Google Scholar 

  24. Couturier JL, Nicolson R. A retrospective assessment of citalo-pram in children and adolescents with pervasive developmental disorders. J Child Adolesc Psychopharmacol 2002 Fall; 12(3): 243–8

    Article  PubMed  Google Scholar 

  25. Namerow LB, Thomas P, Bostic JQ, et al. Use of citalopram in pervasive developmental disorders. J Dev Behav Pediatr 2003 Apr; 24(2): 104–8

    Article  PubMed  Google Scholar 

  26. Hollander E, Kaplan A, Cartwright C, et al. Venlafaxine in children, adolescents and adults with autism spectrum disorder: an open retrospective clinical report. J Child Neurol 2000 Feb; 15(2): 132–5

    Article  PubMed  CAS  Google Scholar 

  27. Posey DJ, Guenin KD, Kohn AE, et al. A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders. J Child Adolesc Psychopharmacol 2001 Fall; 11(3): 267–77

    Article  PubMed  CAS  Google Scholar 

  28. Biederman J, Baldessarini R, Goldblatt A, et al. A naturalistic study of 24-hour electrocardiographic recordings in children and adolescents treated with desipramine. J Am Acad Child Adolesc Psychiatry 1993 Jul; 32(4): 805–13

    Article  PubMed  CAS  Google Scholar 

  29. Sanchez LE, Campbell M, Small AM, et al. A pilot study of clomipramine in young autistic children. J Am Acad Child Adolesc Psychiatry 1996 Apr; 35(4): 537–44

    Article  PubMed  CAS  Google Scholar 

  30. Brasic JR, Barnett JY, Kaplan D, et al. Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation. Neurology 1994 Jul; 44(7): 1309–12

    Article  PubMed  CAS  Google Scholar 

  31. Remington G, Sloman L, Konstantareas M, et al. Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo controlled, crossover study. J Clin Psychopharmacol 2001 Aug; 21(4): 440–4

    Article  PubMed  CAS  Google Scholar 

  32. Fatemi SH, Realmuto GM, Khan L, et al. Fluoxetine in the treatment of adolescent patients with autism: a longitudinal open trial. J Autism Dev Disord 1998; 29(4): 303–7

    Article  Google Scholar 

  33. DeLong GR, Teague LA, Kamran MM. Effects of fluoxetine treatment in young children with idiopathic autism. Dev Med Child Neurol 1998 Aug; 40(8): 551–62

    Article  PubMed  CAS  Google Scholar 

  34. Snead RW, Boon F, Presberg J. Paroxetine for self-injurious behavior. J Am Acad Child Adolesc Psychiatry 1994 Jul–Aug; 33(6): 909–10

    Article  PubMed  CAS  Google Scholar 

  35. Posey DI, Litwiller M, Koburn A, et al. Paroxetine in autism. J Am Acad Child Adolesc Psychiatry 1999 Feb; 38(2): 111–2

    Article  PubMed  CAS  Google Scholar 

  36. McDougle CJ, Naylor ST, Cohen DJ, et al. A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psychiatry 1996 Nov; 53(11): 1001–8

    Article  PubMed  CAS  Google Scholar 

  37. McDougle CJ, Scahill L, McCracken JT, et al. Research units on pediatric psychopharmacology-autism network: background and rationale for an initial controlled study of risperidone. Child Adolesc Psychiatr Clin N Am 2000 Jan; 9(1): 201–24

    PubMed  CAS  Google Scholar 

  38. Chugani DC, Muzik O, Behen M, et al. Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol 1999 Mar; 45(3): 287–95

    Article  PubMed  CAS  Google Scholar 

  39. Gillberg C, Svennerholm L, Hamilton-Hellberg C. Childhood psychosis and monoamine metabolites in spinal fluid. J Autism Dev Disord 1983 Dec; 13(4): 383–96

    Article  PubMed  CAS  Google Scholar 

  40. Campbell M, Anderson L, Meier M, et al. A comparison of haloperidol and behavior therapy and their interaction in autistic children. J Am Acad Child Psychiatry 1978 Autumn; 17(4): 640–55

    Article  PubMed  CAS  Google Scholar 

  41. Anderson L, Campbell M, Grega D, et al. Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms. Am J Psychiatry 1984 Oct; 141(10): 1195–202

    PubMed  CAS  Google Scholar 

  42. Anderson L, Campbell M, Adams P, et al. The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. J Autism Dev Disord 1989 Jun; 19(2): 227–39

    Article  PubMed  CAS  Google Scholar 

  43. Perry R, Campbell M, Adams P, et al. Long-term efficacy of haloperidol in autistic children: continuous versus discontinuous drug administration. J Am Acad Child Adolesc Psychiatry 1998 Jan; 28(1): 87–92

    Article  CAS  Google Scholar 

  44. 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 

  45. Naruse H, Nagahata M, Nakane Y. A multi-center double-blind trial of pimozide (Orap), haloperidol and placebo in children with behavior disorders, using cross-over design. Acta Paedopsychiatr 1982; 48: 173–84

    PubMed  CAS  Google Scholar 

  46. Kumra S, Frazier JA, Jacobsen LK, et al. Childhood-onset schizophrenia: a double-bline clozapine-haloperidol comparison. Arch Gen Psychiatry 1996; 53(12): 1090–7

    Article  PubMed  CAS  Google Scholar 

  47. Meltzer HY, Matsubara S, Lee J-C. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D1, D2 and serotonin 2 pKi values. J Pharmacol Exp Ther 1989 Oct; 251(1): 238–46

    PubMed  CAS  Google Scholar 

  48. Kapur S, Seeman P. Does fast dissociation from the dopamine d (2) receptor explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry 2001 Mar; 158(3): 360–9

    Article  PubMed  CAS  Google Scholar 

  49. Fisman S, Steele M. Use of risperidone in pervasive developmental disorders: a case series. J Child Adolesc Psychopharmacol 1996 Summer; 6(2): 177–90

    Article  PubMed  CAS  Google Scholar 

  50. Zuddas A, Ledda MG, Fratta A, et al. Clinical effects of clozapine on autistic disorder. Am J Psychiatry 1996 May; 153(5): 738

    PubMed  CAS  Google Scholar 

  51. 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 Feb; 19(1): 37–44

    Article  PubMed  CAS  Google Scholar 

  52. Malone RP, Cater J, Sheikh RM, et al. Olanzapine versus haloperidol in children with autistic disorder: an open pilot study. J Am Acad Child Adolesc Psychiatry 2001 Aug; 40(8): 887–94

    Article  PubMed  CAS  Google Scholar 

  53. 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 

  54. Martin A, Scahill L, Keonig K, et al. An open-label trial of quetiapine in children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol 1999; 9(2): 99–107

    Article  PubMed  CAS  Google Scholar 

  55. 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 Aug; 41(8): 921–7

    Article  PubMed  Google Scholar 

  56. Research Units on Pediatric Psychopharmachology (RUPP) Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002 Aug; 347(5): 314–21

    Article  Google Scholar 

  57. 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 May; 36(5): 685–93

    Article  PubMed  CAS  Google Scholar 

  58. Nicolson R, Awad G, Sloman L. An open trial of risperidone in young autistic children. J Am Acad Child Adolesc Psychiatry 1998 Apr; 37(4): 372–6

    Article  PubMed  CAS  Google Scholar 

  59. Malone RP, 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 Feb; 41(2): 140–7

    Article  PubMed  Google Scholar 

  60. 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 

  61. Chen NC, Bedair HS, McKay B, et al. Clozapine in the treatment of aggression in an adolescent with autistic disorder. J Clin Psychiatry 2001 Jun; 62(6): 479–80

    Article  PubMed  CAS  Google Scholar 

  62. McDougle CJ, Holmes JP, Carlson DC, et al. A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Arch Gen Psychiatry 1998 Jul; 55(7): 633–41

    Article  PubMed  CAS  Google Scholar 

  63. Hardan A, Johnson K, Johnson C, et al. Risperidone treatment of children and adolescents with developmental disorders. J Am Acad Child Adolesc Psychiatry 1996 Nov; 35(11): 1551–6

    Article  PubMed  CAS  Google Scholar 

  64. Perry R, Pataki C, Munoz-Silva DM, et al. Risperidone in children and adolescents with pervasive developmental disorder: pilot trial and follow-up. J Child Adolesc Psychopharmacol 1997; 7(3): 167–79

    Article  PubMed  CAS  Google Scholar 

  65. Findling RL, Maxwell K, Wiznitzer M. An open clinical trial of risperidone monotherapy in young children with autistic disorder. Psychopharmacol Bull 1997; 33(1): 155–9

    PubMed  CAS  Google Scholar 

  66. Zuddas A, Di Martino A, Muglia P, Cianchetti C. Long-term risperidone for pervasive developmental disorder: efficacy, tolerability, and discontinuation. J Child Adolesc Psychopharmacol 2000 Summer; 10(2): 79–90

    Article  PubMed  CAS  Google Scholar 

  67. Casaer P, Walleghem D, Vandenbussche I, et al. Pharmacokinetics and safety of risperidone in autistic children [abstract]. Ped Neurol 1994; 11:89

    Article  Google Scholar 

  68. Demb HB. Risperidone in young children with pervasive developmental disorders and other developmental disabilities. J Child Adolesc Psychopharmacol 1996 Spring; 6(1): 79–80

    Article  PubMed  CAS  Google Scholar 

  69. Schwamm JS, Klass E, Alonso C, et al. Risperidone and refusal to eat. J Am Acad Child Adolesc Psychiatry 1998 Jun; 37(6): 572–3

    Article  Google Scholar 

  70. Posey DJ, Walsh KH, Wilson GA, et al. Risperidone in the treatment of two very young children with autism. J Child Adolesc Psychopharmacol 1999 Apr; 9(4): 273–6

    Article  PubMed  CAS  Google Scholar 

  71. Masi G, Cosenza A, Mucci M, et al. Risperidone monotherapy in preschool children with pervasive developmental disorders: an open label study. J Child Neurol 2001 Jun; 16(6): 395–400

    PubMed  CAS  Google Scholar 

  72. Masi G, Cosenza A, Mucci M. Open trial of risperidone in 24 young children with pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry 2001 Oct; 40(10): 1206–14

    Article  PubMed  CAS  Google Scholar 

  73. Vitiello B. Pediatric psychopharmacology and the interaction between drugs and the developing brain. Can J Psychiatry 1998 Aug; 43(6): 582–4

    PubMed  CAS  Google Scholar 

  74. Greenhill LL, Jensen PS, Abikoff H, et al. Developing strategies for psychopharmacological studies in preschool children. J Am Acad Child Adolesc Psychiatry 2003; 42(4): 406–14

    Article  PubMed  Google Scholar 

  75. Horrigan JP, Barnhill LJ, Courvoisie HE. Olanzapine in PDD. J Am Acad Child Adolesc Psychiatry 1997 Sep; 36(9): 1166–7

    Article  PubMed  CAS  Google Scholar 

  76. Rubin M. Use of atypical antipsychotics in children with mental retardation, autism and other developmental disabilities. Psychiatr Ann 1997; 27: 19–221

    Google Scholar 

  77. Malek-Ahmadi P, Simonds JF. Olanzapine for autistic disorder with hyperactivity [letter]. J Am Acad Child Adolesc Psychiatry 1998 Sep; 37(9): 902

    Article  PubMed  CAS  Google Scholar 

  78. 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; 161(6): 1125–7

    Article  PubMed  Google Scholar 

  79. Stigler KA, Potenza MN, Posey DJ, et al. Weight gain associated with atypical antipsychotic use in children and adolescents: prevalence, clinical relevance, and management. Paediatr Drugs 2004; 6(1): 33–44

    Article  PubMed  Google Scholar 

  80. 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): 205–19

    Article  PubMed  CAS  Google Scholar 

  81. Lessig MC, Shapira NA, Murphy TK. Topiramate for reversing atypical antipsychotic weight gain [letter]. J Am Acad Child Adolesc Psychiatry 2001 Dec; 40(12): 1364

    Article  PubMed  CAS  Google Scholar 

  82. 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): 271–3

    Article  PubMed  Google Scholar 

  83. Wudarski 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  Google Scholar 

  84. Frazier JA, Meyer MC, Biederman J, et al. Risperidone treatment for juvenile bipolar disorder: a retrospective chart review. J Am Acad Child Adolesc Psychiatry 1999 Aug; 38(8): 960–5

    Article  PubMed  CAS  Google Scholar 

  85. Masi G, Cosenza A, Mucci M. Prolactin levels in preschool autistic children during risperidone treatment. J Child Adolesc Psychopharmacol 2001 Winter; 11(4): 389–94

    Article  PubMed  CAS  Google Scholar 

  86. Findling RL, Kusumakar V, Daneman D, et al. Prolactin levels during long-term risperidone treatment in children and adolescents. J Clin Psychiatry 2003; 64(11): 1362–9

    Article  PubMed  CAS  Google Scholar 

  87. 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 

  88. Galli-Tsinopoulou A, Nousia-Arvanitakis S, Mitsiakos G, et al. Osteopenia in children and adolescents with hyperprolactinemia. J Pediatr Endocrinol Metab 2000 Apr; 13(4): 439–41

    Article  PubMed  CAS  Google Scholar 

  89. Mandoki MW. Risperidone treatment of children and adolescents: increased risk of extrapyramidal side effects? J Child Adolesc Psychopharmacol 1995; 5(1): 49–67

    Article  Google Scholar 

  90. Amann BL, Pogarell O, Mergl R, et al. EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects. Hum Psychopharmacol 2003; 18(8): 641–6

    Article  PubMed  CAS  Google Scholar 

  91. 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 

  92. Volkmar FR, Nelson DS. Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry 1990 Jan; 29(1): 127–9

    Article  PubMed  CAS  Google Scholar 

  93. 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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  95. 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 

  96. Hedenmalm K, Hagg S, Stahl M, et al. Glucose intolerance with atypical antipsychotics. Drug Saf 2002; 25(15): 1107–16

    Article  PubMed  CAS  Google Scholar 

  97. Wirshing DA, Boyd JA, Meng LR, et al. The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry 2002 Oct; 63(10): 856–65

    Article  PubMed  CAS  Google Scholar 

  98. Koller EA, Cross JT, Doraiswamy PM, et al. Risperidone-associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy 2003 Jun; 23(6): 735–44

    Article  PubMed  CAS  Google Scholar 

  99. 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 

  100. 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 

  101. Woods SW, Martin A, Spector SG, et al. Effects of development on olanzapine-associated adverse events. J Am Acad Child Adolesc Psychiatry 2002 Jul–Aug; 26(7–8): 1409–11

    Google Scholar 

  102. Panksepp J. A neurochemical theory of autism. Trends Neurosci 1979; 2: 174–7

    Article  Google Scholar 

  103. Leboyer M, Bouvard MP, Launay JM, et al. A double-blind study of naltrexone in infantile autism. J Autism Dev Disord 1992 Jun; 22(2): 309–19

    Article  PubMed  CAS  Google Scholar 

  104. Gillberg C. Endogenous opioid and opiate antagonists in autism: brief review of empirical findings and implications for clinicians. Dev Med Child Neurol 1995 Mar; 37(3): 239–45

    Article  PubMed  CAS  Google Scholar 

  105. Sandman CA, Barron JL, Chicz-DeMet A, et al. Brief report: plasma beta-endorphin and cortisol levels in autistic patients. J Autism Dev Disord 1991 Mar; 21(1): 83–8

    Article  PubMed  CAS  Google Scholar 

  106. Willemsen-Swinkels SHN, Buitelaar JK, van Engeland H. The effects of chronic naltrexone treatment in young autistic children: a double-blind placebo-controlled crossover study. Biol Psychiatry 1996 Jun; 39(12): 1023–31

    Article  PubMed  CAS  Google Scholar 

  107. Campbell M, Anderson LT, Small AM, et al. Naltrexone in autistic children: behavioral symptoms and attentional learning. J Am Acad Child Adolesc Psychiatry 1993 Nov; 32(6): 1283–91

    Article  PubMed  CAS  Google Scholar 

  108. Kolmen BK, Feldman HM, Handen BL, et al. Naltrexone in young autistic children: a double blind, placebo-controlled, cross-over study. J Am Acad Child Adolesc Psychiatry 1995 Feb; 34(2): 223–31

    Article  PubMed  CAS  Google Scholar 

  109. Jaselskis CA, Cook Jr EH, Fletcher KE, et al. Clonidine treatment of hyperactive and impulsive children with autistic disorder. J Clin Psychopharmacol 1992 Oct; 12(5): 322–7

    Article  PubMed  CAS  Google Scholar 

  110. Posey DJ, Decker J, Sasher TM, et al. A retrospective analysis of guanfacine in the treatment of autism [abstract no.816]. American Psychiatric Association Annual Meeting; 2001 May 5–10; New Orleans

  111. Handen BL, Johnson CR, Lubetsky M. Efficacy of methylphenidate among children with autism and symptoms of attentiondeficit hyperactivity disorder. J Autism Dev Disord 2000 Jun; 30(3): 245–55

    Article  PubMed  CAS  Google Scholar 

  112. Hollander E, Dolgoff-Kaspar R, Cartwright C, et al. An open-trial of divalproex sodium in autism spectrum disorders. J Clin Psychiatry 2001; 62(7): 530–4

    Article  PubMed  CAS  Google Scholar 

  113. Belsito KM, Law PA, Kirk KS, et al. Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord 2001 Apr; 31(2): 175–81

    Article  PubMed  CAS  Google Scholar 

  114. Buitelaar JK, van der Gaag RJ, van der Hoeven J. Buspirone in the management of anxiety and irritability in children with pervasive developmental disorder: results of an open label study. J Clin Psychiatry 1998 Feb; 59(2): 56–9

    Article  PubMed  CAS  Google Scholar 

  115. King BH, Wright DM, Habden J, et al. Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder. J Am Acad Child Adolesc Psychiatry 2001 Jun; 40(6): 658–65

    Article  PubMed  CAS  Google Scholar 

  116. Dunn-Geier J, Ho HH, Auersperg E, et al. Effect of secretin on children with autism: a randomized controlled trial. Dev Med Child Neurol 2000 Dec; 42(12): 796–802

    PubMed  CAS  Google Scholar 

  117. Roberts W, Weaver L, Brian J, et al. Repeated doses of porcine secretin in the treatment of autism: a randomized, placebo-controlled trial. Pediatrics 2001 May; 107(5): E71

    Article  PubMed  CAS  Google Scholar 

  118. Fankhauser MP, Karumanchi VC, German ML, et al. A doubleblind, placebo-controlled study of the efficacy of transdermal clonidine in autism. J Clin Psychiatry 1992 Mar; 53(3): 77–82

    PubMed  CAS  Google Scholar 

  119. McCracken JT, Martin W. Clonidine side effect [letter]. J Am Acad Child Adolesc Psychiatry 1997; 36(2): 160–1

    Article  PubMed  CAS  Google Scholar 

  120. Cohen DJ, Riddle MA, Leckman JF. Pharmacotherapy of Tourette’s syndrome and associated disorders. Psychiatr Clin North Am 1992; 15(1): 109–29

    PubMed  CAS  Google Scholar 

  121. Quintana H, Birmaher B, Stedge D, et al. Use of methylphenidate in the treatment of children with autistic disorder. J Autism Dev Disord 1995 Jun; 25(3): 283–94

    Article  PubMed  CAS  Google Scholar 

  122. Aman MG, Marks RE, Turbott SH, et al. Clinical effects of methylphenidate and thioridazine in intellectually subaverage children. J Am Acad Child Adolesc Psychiatry 1991 Mar; 30(2): 246–56

    Article  PubMed  CAS  Google Scholar 

  123. Di Martino A, Melis G, Cianchetti C, et al. Methylphenidate for pervasive developmental disorders. Safety and efficacy of acute single dose test and ongoing therapy: an open-pilot study. J Child Adolesc Psychopharmacol 2004; 14(2): 207–18

    Google Scholar 

  124. Wozniak J, Biederman J, Faraone SV, et al. Mania in children with pervasive developmental disorders revisited. J Am Acad Child Adolesc Psychiatry 1997 Nov; 36(11): 1552–9

    PubMed  CAS  Google Scholar 

  125. Kerbeshian J, Burd L, Fisher W. Lithium carbonate in the treatment of two patients with infantile autism and atypical bipolar disorder. J Clin Psychopharmacol 1987 Dec; 7(6): 401–5

    Article  PubMed  CAS  Google Scholar 

  126. Steingard R, Biederman J. Lithium-responsive manic-like symptoms in two individuals with autism and mental retardation. J Am Acad Child Adolesc Psychiatry 1987 Nov; 26(6): 932–5

    Article  PubMed  CAS  Google Scholar 

  127. Epperson CN, McDougle CJ, Anand A, et al. Lithium augmentation of fluvoxamine in autistic disorder: a case report. J Child Adolesc Psychopharmacol 1994; 4: 201–7

    Article  Google Scholar 

  128. Uvebrant P, Bauziene R. Intractable epilepsy in children: the efficacy of lamotrigine treatment, including non-seizure-related benefits. Neuropediatrics 1994 Dec; 25(6): 284–9

    Article  PubMed  CAS  Google Scholar 

  129. Carlsson ML. Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate-serotonin interactions for pharmacotherapy. J Neural Transm 1998; 105(4–5): 525–35

    Article  PubMed  CAS  Google Scholar 

  130. Rossi PG, Posar A, Parmeggiani A, et al. Niaprazine in the treatment of autistic disorder. J Child Neurol 1999 Aug; 14(8): 547–50

    Article  PubMed  CAS  Google Scholar 

  131. Rimland B, Callaway E, Dreyfus P. The effect of high doses of vitamin B6 on autistic children. Am J Psychiatry 1978 Apr; 135(4): 472–5

    PubMed  CAS  Google Scholar 

  132. Pfeiffer SI, Norton J, Nelson L, et al. Efficacy of vitamin B6 and magnesium in the treatment of autism: a methodology review and summary of outcomes. J Autism Dev Disord 1995 Oct; 25(5): 481–93

    Article  PubMed  CAS  Google Scholar 

  133. Findling RL, Maxwell K, Scotese-Wojtila L, et al. High-dose pyridoxine and magnesium administration in children with autistic disorder: an absence of salutary effects in a double-blind, placebo-controlled study. J Autism Dev Disord 1997 Nov; 27(4): 467–78

    Article  PubMed  CAS  Google Scholar 

  134. Sandier AD, Sutton KA, DeWeese J, et al. Lack of benefit of a single dose of synthetic human secretin in the treatment autism and pervasive developmental disorders. N Engl J Med 1999 Dec; 341(24): 1801–6

    Article  Google Scholar 

  135. Chez MG, Buchanan CP, Bagan BT, et al. Secretin and autism: a two-part clinical investigation. J Autism Dev Disord 2000 Apr; 30(2): 87–94

    Article  PubMed  CAS  Google Scholar 

  136. Owley T, McMahon W, Cook EH, et al. Multisite, double-blind, placebo-controlled trial of porcine secretin in autism J Am Acad Child Adolesc Psychiatry 2001 Nov; 40(11): 1293–9

    Article  PubMed  CAS  Google Scholar 

  137. Coniglio SJ, Lewis JD, Lang C, et al. A randomized, double-blind, placebo-controlled trial of single-dose intravenous secretin treatment for children with autism. J Pediatr 2001 May; 138(5): 649–55

    Article  PubMed  CAS  Google Scholar 

  138. Vitiello B, Jensen PS. Developmental perspectives in pediatric psychopharmacology. Psychopharmacol Bull 1995; 31(1): 75–81

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No financial support was used for the preparation of this manuscript. Dr Masi is a consultant of Eli Lilly and has received research support from Eli Lilly for studies on ADHD; he has also served on advisory boards on ADHD for Eli Lilly and Janssen.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gabriele Masi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Masi, G. Pharmacotherapy of Pervasive Developmental Disorders in Children and Adolescents. CNS Drugs 18, 1031–1052 (2004). https://doi.org/10.2165/00023210-200418140-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-200418140-00006

Keywords

Navigation