Psychopharmacology

, Volume 191, Issue 1, pp 5–13 | Cite as

Research in child and adolescent psychopharmacology: recent accomplishments and new challenges

Review

Abstract

Rationale

Research in pediatric psychopharmacology has expanded considerably in the last 10 years. Still, controversy remains about the effectiveness and safety of commonly used psychotropics and their role in child treatment, thus pointing to the need for more in-depth and targeted investigations.

Objectives

To review recent accomplishments and current limitations of pediatric psychopharmacology, and discuss approaches to further research.

Methods

Selective review of the relevant literature and research in progress.

Results

Controlled clinical trials have been conducted in many common psychiatric disorders in children and adolescents, thus providing a basis on which evidence-based treatment guidelines can be constructed. Little innovation has, however, occurred in treatment development and testing. Safety concerns are prominent and have a major influence on clinical practice and drug utilization.

Conclusions

While a research infrastructure has been successfully built for conducting pediatric clinical trials, important aspects such as long-term treatment effects, optimal sequencing and individualization of interventions, and integration of neuroscience findings into innovative, theory-driven treatment development remain to be addressed.

Keywords

Psychopharmacology Children Adolescents Research 

Notes

Disclaimer

The opinions and assertions contained in this chapter are the private views of the author and are not to be construed as official or as reflecting the views of the National Institute of Mental Health, the National Institutes of Health, or the Department of Health and Human Services.

References

  1. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DCGoogle Scholar
  2. Amitai Y, Frischer H (2006) Excess fatality from desipramine in children and adolescents. J Am Acad Child Adolesc Psychiatry 45:54–60CrossRefPubMedGoogle Scholar
  3. Angold A, Erkanli A, Egger HL, Costello EJ (2002) Stimulant treatment for children: a community perspective. J Am Acad Child Adolesc Psychiatry 39:975–984Google Scholar
  4. Axelson DA, Perel JM, Birmaher B, Rudolph GR, Nuss S, Bridge J, Brent DA (2002) Sertraline pharmacokinetics and dynamics in adolescents. J Am Acad Child Adolesc Psychiatry 41:1037–1044CrossRefPubMedGoogle Scholar
  5. Barkley RA, Fischer M, Smallish L, Fletcher K (2004) Young adult follow-up of hyperactive children: antisocial activities and drug use. J Child Psychol Psychiatry 45:195–211CrossRefPubMedGoogle Scholar
  6. Barkley RA, Fischer M, Smallish L, Fletcher K (2006) Young adult outcome of hyperactive children: adaptive functioning in major life activities. J Am Acad Child Adolesc Psychiatry 45:192–202CrossRefPubMedGoogle Scholar
  7. Biederman J, Thisted RA, Greenhill LL, Ryan ND (1995) Estimation of the association between desipramine and the risk for sudden death in 5- to 14-year-old children. J Clin Psychiatry 56:87–93PubMedGoogle Scholar
  8. Biederman J, Wilens T, Mick E, Spencer T, Faraone S (1999) Pharmacotherapy of attention-deficit/hyperactivity disorder reduces the risk for substance abuse disorder. Pediatrics 104:e20CrossRefPubMedGoogle Scholar
  9. Blumer J (1999) Off-label uses of drugs in children. Pediatrics 104:598–602PubMedGoogle Scholar
  10. Bolanos CA, Barrot M, Berton O, Wallace-Black D, Nestler EJ (2003) Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood. Biol Psychiatry 54:1317–1329CrossRefPubMedGoogle Scholar
  11. Bradley C (1937) The behavior of children receiving Benzedrine. Am J Psychiatry 94:577–585Google Scholar
  12. Brent DA (2004) Antidepressants and pediatric depression—the risk of doing nothing. N Engl J Med 351:1598–1601CrossRefPubMedGoogle Scholar
  13. Bryant AE, Dreifuss FE (1996) Valproic acid hepatic fatalities. III. U.S. experience since 1986. Neurology 46:465–469PubMedGoogle Scholar
  14. Carlezon WA, Mague SD, Andersen SL (2003) Enduring behavioral effects of early exposure to methylphenidate in rats. Biol Psychiatry 54:1330–1337CrossRefPubMedGoogle Scholar
  15. Costello EJ, Mustillo S, Erkanli A, Keeler G, Angold A (2003) Prevalence and development of psychiatric disorders in childhood and adolescence. Arch Gen Psychiatry 60:837–844PubMedCrossRefGoogle Scholar
  16. Cohen SN (1999) The Pediatric Pharmacology Research Unit (PPRU) Network and its role in meeting pediatric labeling needs. Pediatrics 104:644–645CrossRefPubMedGoogle Scholar
  17. Cox ER, Motheral BR, Henderson RR, Mager D (2003) Geographic variation in the prevalence of stimulant medication use among children 5 to 14 years old: results from a commercially insured US sample. Pediatrics 111:237–243CrossRefPubMedGoogle Scholar
  18. Curry JF, Rohde R, Simons A, Silva SG, Vitiello B, Kratochvil CJ, March JS, Reinecke MA, Feeny N, Wells KC, Pathak S, Weller E, Rosenberg D, Kennard BD, Robins M, Ginsburg GS, TADS Team (2006) Predictors and moderators of acute outcome in the Treatment for Adolescents with Depression Study (TADS). J Am Acad Child Adolesc Psychiatry (in press)Google Scholar
  19. DeVeaugh-Geiss J, March J, Andreason P, Clary C, Emslie G, Ford L, Greenhill L, Murphy D, Prentice E, Roberts R, Silva S, Swanson S, van Zwieten-Boot B, Vitiello B, Wagner KD, Shapiro M, Mangum B (2006) A workshop on child and adolescent psychopharmacology in the new millennium. J Am Acad Child Adolesc Psychiatry 45:261–270CrossRefPubMedGoogle Scholar
  20. El-Zein RA, Abdel-Rahman SZ, Hay MJ, Lopez MS, Bondy ML, Morris DL, Legator MS (2005) Cytogenetic effects in children treated with methylphenidate. Cancer Lett 230:284–291CrossRefPubMedGoogle Scholar
  21. Emslie GJ, Heiligenstein JH, Wagner KD, Hoog SL, Ernest DE, Brown E, Nilsson M, Jacobson JG (2002) Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial. J Am Acad Child Adolesc Psychiatry 41:1205–1215CrossRefPubMedGoogle Scholar
  22. Emslie GJ, Heiligenstein JH, Hoog SL, Wagner KD, Findling RL, McCracken JT, Nilsson ME, Jacobson JG (2004) Fluoxetine treatment for prevention of relapse of depression in children and adolescents: a double-blind, placebo-controlled study. J Am Acad Child Adolesc Psychiatry 43:1397–1405CrossRefPubMedGoogle Scholar
  23. Faber A, de Jong-van den Berg LTW, can den Berg PB, Tobi H (2005) Psychotropic co-medication among stimulant-treatment children in the Netherlands. J Child Adolesc Psychopharmacol 15:38–43CrossRefPubMedGoogle Scholar
  24. Farwell JR, Lee YJ, Hirtz DG et al (1990) Phenobarbital for febrile seizures-effects on intelligence and on seizure recurrence. N Engl J Med 322:364–369PubMedCrossRefGoogle Scholar
  25. Fegert JM, Koelch M, Zito JM, Glaeske G, Janhsen K (2006) Antidepressant use in children and adolescents in Germany. J Child Adolesc Psychopharmacol 16:197–206CrossRefPubMedGoogle Scholar
  26. Findling RL, Reed MD, Myers C, O’Riordan MA, Fiala S, Branicky LA, Waldorf B, Blumer JL (1999) Paroxetine pharmacokinetics in depressed children and adolescents. J Am Acad Child Adolesc Psychiatry 38:952–959CrossRefPubMedGoogle Scholar
  27. Fombonne E, Wostear G, Cooper V, Harrington R, Rutter M (2001) The Maudsley long-term follow-up of child and adolescent depression. 2. Suicidality, criminality and social dysfunction in adulthood. Br J Psychiatry 179:218–223CrossRefPubMedGoogle Scholar
  28. Food and Drug Administration (2005) FDA Alert: Adderall and Adderall XR (amphetamines)—Information (February 10, 2005). Available at Website: http://www.fda.gov/cder/drug/infopage/adderall/default.htm
  29. Food and Drug Administration (2006) Approved moieties to which FDA has issued a written request for pediatric studies under section 505A of the Federal Food, Drug, and Cosmetic Act. Available at: http://www.fda.gov/cder/pediatric/wrstats.htm (Last updated February 28, 2006; accessibility verified March 31, 2006)
  30. Geller DA, Wagner KD, Emslie G, Murphy T, Carpenter D, Wetherhold E, Perera P, Machin A, Gardiner C (2004) Paroxetine treatment in children and adolescents with obsessive–compulsive disorder: a randomized, multicenter, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 43:1387–1396CrossRefPubMedGoogle Scholar
  31. Greenhill LL, Pliszka S, Dulcan M, Bernet W, Arnold V, Beitchman J, Benson RS, Bukstein O, Kinlan J, McClellan J, Rue D, Shaw JA, Stock S, American Academy of Child and Adolescent Psychiatry (2002) Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry 41(2 Suppl):26S–49SPubMedGoogle Scholar
  32. Greenhill LL, Vitiello B, Riddle MA, Fisher P, Shockey E, March JS, Levine J, Fried J, Abikoff H, Zito JM, McCracken JT, Findling RL, Robinson J, Cooper TB, Davies M, Varipatis E, Labellarte MJ, Scahill L, Walkup JT, Capasso L, Rosengarten J (2003) Review of safety assessment methods used in pediatric psychopharmacology. J Am Acad Child Adolesc Psychiatry 42:627–633CrossRefPubMedGoogle Scholar
  33. Greenhill LL, Vitiello B, Fisher P, Levine J, Davies M, Abikoff HB, Chuang S, Findling RL, March JS, Scahill L, Walkup J, Riddle MA (2004) Comparison of increasingly detailed elicitation methods for the assessment of adverse events in pediatric psychopharmacology. J Am Acad Child Adolesc Psychiatry 43:1488–1496CrossRefPubMedGoogle Scholar
  34. Greenhill LL, Abikoff H, Chuang S, Cooper T, Cunningham C, Davies M, Ghuman J, Kollins S, McCracken JT, McGough J, Posner K, Riddle MA, Skrobala A, Swanson A, Vitiello B, Wigal S, Wigal T (2006) Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry (in press)Google Scholar
  35. Hammad TA, Laughren T, Racoosin J (2006) Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 63:332–339CrossRefPubMedGoogle Scholar
  36. Hazell P, O'Connell D, Heathcote D, Henry D (2002) Tricyclic drugs for depression in children and adolescents. Cochrane Database Syst Rev 2:CD002317Google Scholar
  37. Insel TR, Quirion R (2005) Psychiatry as a clinical neuroscience discipline. JAMA 294:1221–2224CrossRefGoogle Scholar
  38. Jensen PS, Kettle L, Roper M, Sloan MT, Dulcan MK, Hoven C, Bird HR, Bauermeister JJ, Payne JD (1999) Are stimulants overprescribed? Treatment of ADHD in four U.S. communities. J Am Acad Child Adolesc Psychiatry 38:797–804CrossRefPubMedGoogle Scholar
  39. Jensen PS, Garcia JA, Glied S, Crowe M, Foster M, Schlander M, Hinshaw S, Vitiello B, Arnold LE, Elliott G, Hechtman L, Newcorn JH, Pelham WE, Swanson J, Wells K (2005) Cost-effectiveness of ADHD treatments: findings from the Multimodal Treatment Study of Children with ADHD. Am J Psychiatry 162:1628–1636CrossRefPubMedGoogle Scholar
  40. Kessler RC, Berglund P, Delmer O, Jin R, Merikangas KR, Walters EE (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:593–602CrossRefPubMedGoogle Scholar
  41. Kollins SH, Greenhill LL, Swanson S, Wigal S, Abikoff H, McCracken JT, Riddle M, McGough JJ, Vitiello B, Wigal T, Skrobala AM, Posner K, Ghuman JK, Davies M, Cunningham C, Bauzo A (2006) Rationale, Design, and Methods of the Preschool ADHD Treatment Study (PATS). J Am Acad Child Adolesc Psychiatry (in press)Google Scholar
  42. Kowatch RA, Fristad M, Birmaher B, Wagner KD, Findling RL, Hellander M (2005) Treatment guidelines for children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 44:213–235CrossRefPubMedGoogle Scholar
  43. Kratochvil CJ, Vitiello B, Walkup J, Emslie G, Waslick BD, Weller EB, Burke WJ, March JS (2006) SSRIs in pediatric depression: is the balance between benefits and risks favorable? J Child Adolesc Psychopharmacol 16:11–24CrossRefPubMedGoogle Scholar
  44. Leibson CL, Katusic SK, Barbaresi WJ, Ransom J, O’Brien PC (2001) Use and costs of medical care for children and adolescents with and without attention-deficit/hyperactivity disorder. JAMA 285:60–66CrossRefPubMedGoogle Scholar
  45. Lieberman JA, Perkins D, Belger A, Chakos M, Jarkkog F, Boteva K, Gilmore J (2001) The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol Psychiatry 50:884–897CrossRefPubMedGoogle Scholar
  46. March JS, Silva SG, Compton S, Anthony G, DeVeaugh-Geiss J, Califf R, Krishnan R (2004) The Child and Adolescent Psychiatry Trials Network (CAPTN). J Am Acad Child Adolesc Psychiatry 43:515–518CrossRefPubMedGoogle Scholar
  47. March J, Silva S, Compton S, Shapiro M, Califf R, Krishnan KR (2005) The case for practical clinical trials in psychiatry. Am J Psychiatry 162:836–846CrossRefPubMedGoogle Scholar
  48. Martin A, Scahill L, Charney D, Leckman JF (2003) Child and Adolescent Psychopharmacology. Oxford University Press, New York, NYGoogle Scholar
  49. McGough JJ (2005) Attention-deficit/hyperactivity disorder pharmacogenomics. Biol Psychiatry 57:1367–1373CrossRefPubMedGoogle Scholar
  50. Mosholder A, Willy M (2006) Suicidal adverse events in pediatric randomized, controlled clinical trials of antidepressants drugs are associated with active drugs treatment: a meta-analysis. J Child Adolesc Psychopharmacol 16:25–32CrossRefPubMedGoogle Scholar
  51. MTA Cooperative Group (1999a) A 14-Month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder (ADHD). Arch Gen Psychiatry 56:1073–1086CrossRefGoogle Scholar
  52. MTA Cooperative Group (1999b) Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder (ADHD). Arch Gen Psychiatry 56:1088–1096CrossRefGoogle Scholar
  53. Murray C, Lopez A (1997) Alternative projections of mortality and disability by cause 1999–2020: global burden of disease study. Lancet 349:1498–1504CrossRefPubMedGoogle Scholar
  54. Murray ML, Thompson M, Santosh PJ, Wong IC (2005) Effects of the committee on safety of medicines advice on antidepressant prescribing to children and adolescents in the UK. Drug Saf 28:1151–1157CrossRefPubMedGoogle Scholar
  55. National Institute of Mental Health (2001) Blueprint for Change: Research on Child and Adolescent Mental Health. Report of the National Advisory Mental Health Council’s Workgroup on Child and Adolescent Mental Health Intervention Development and Deployment. Washington, DC (Available at Web site: http://www.nimh.nih.gov/publicat/nimhblueprint.pdf; access verified on March 31, 2006)
  56. National Institute of Mental Health (2005) Treatment Research in Mental Illness: Improving the Nation’s Public Mental Health Care through NIMH Funded Interventions Research. Report of the National Advisory Mental Health Council’s Workgroup on Clinical Trials. (Available at Web site: http://www.nimh.nih.gov/council/interventions_research.pdf; access verified on March 31, 2006)
  57. Nissen SE (2006) ADHD drugs and cardiovascular risk. N Engl J Med 354:1445–1448CrossRefPubMedGoogle Scholar
  58. Olfson M, Marcus SC, Weissman MM, Jensen PS (2002) National trends in the use of psychotropic medications by children. J Am Acad Child Adolesc Psychiatry 41:514–521CrossRefPubMedGoogle Scholar
  59. Pediatric OCD Treatment Study (POTS) Team (2004) Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive–compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. JAMA 292(16):1969–1976CrossRefGoogle Scholar
  60. Popper CW (1995) Combining methylphenidate and clonidine: Pharmacologic questions and news reports about sudden death. J Child Adolesc Psychopharmacol 5:157–167CrossRefGoogle Scholar
  61. Preston RJ, Kollins SH, Swanson JM, Greenhill LL, Vitiello B (2005) Comments on ‘Cytogenetics effects in children treated with methylphenidate’ by El-Zein et al. Cancer Lett 230:292–294CrossRefPubMedGoogle Scholar
  62. Research Units on Pediatric Psychopharmacology (RUPP) Anxiety Study Group (2001) Fluvoxamine for the treatment of anxiety disorders in children and adolescents. N Engl J Med 344:1279–1285CrossRefGoogle Scholar
  63. Riddle MA, Geller B, Ryan N (1993) Another sudden death in a child treated with desipramine. J Am Acad Child Adolesc Psychiatry 32:792–797PubMedCrossRefGoogle Scholar
  64. Rosenberg D,R, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ (2000) Decrease in caudate glutamatergic concentrations in pediatric obsessive compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry 39:1096–1103CrossRefPubMedGoogle Scholar
  65. RUPP Anxiety Study Group (2003) Searching for moderators and mediators of pharmacological treatment effects in children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry 42:13–21CrossRefGoogle Scholar
  66. RUPP Autism Network (2002) Risperidone in children with autism and serious behavioral problems. N Engl J Med 347:314–321CrossRefGoogle Scholar
  67. RUPP Autism Network (2005) A randomized controlled crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry 62:1266–1274CrossRefGoogle Scholar
  68. Rutter M (2005) Incidence of autism spectrum disorders: changes over time and their meaning. Acta Paediatr 94:2–15CrossRefPubMedGoogle Scholar
  69. Safer DJ, Zito JM, Gardner JE (2001) Pemoline hepatoxicity and postmarketing surveillance. J Am Acad Child Adolesc Psychiatry 40:622–629CrossRefPubMedGoogle Scholar
  70. Sandler AD, Sutton KA, DeWeese J, Girardi MA, Sheppard V, Bodfish JW (1999) Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder. N Engl J Med 341:1801–1806CrossRefPubMedGoogle Scholar
  71. Swanson JM, Wigal SB, Wigal T, Sonuga-Barke E, Greenhill LL, Biederman J, Kollins S, Nguyen AS, DeCory HH, Hirshe Dirksen SJ, Hatch SJ; COMACS Study Group (2004) A comparison of once-daily extended-release methylphenidate formulations in children with attention-deficit/hyperactivity disorder in the laboratory school (the COMACS study). Pediatrics 113(3 Pt 1):e206–e216CrossRefPubMedGoogle Scholar
  72. TADS Team (2004) The Treatment for Adolescents with Depression Study (TADS): short-term effectiveness and safety outcomes. JAMA 292:807–820CrossRefGoogle Scholar
  73. Taylor E, Chadwick O, Heptinstall E, Danckaerts M (1996) Hyperactivity and conduct problems as risk factors for adolescent development. J Am Acad Child Adolesc Psychiatry 35:1213–1226CrossRefPubMedGoogle Scholar
  74. Timimi S, Taylor E (2004) ADHD is best understood as a cultural construct. Br J Psychiatry 184:8–9CrossRefPubMedGoogle Scholar
  75. Tourette’s Syndrome Study Group (2002) Treatment of ADHD in children with tics: a randomized controlled trial. Neurology 58:527–536Google Scholar
  76. US Congress (1997) Food and Drug Administration Modernization Act. Public Law 105–115Google Scholar
  77. US Congress (2002) Best Pharmaceuticals for Children Act (BPCA). Public Law 107–109Google Scholar
  78. US Congress (2003) Pediatric Research Equity Act of 2003. Public Law 108–155Google Scholar
  79. US Public Health Service (2000) Report of the surgeon general’s conference on children’s mental health: a national action agenda. Washington, DCGoogle Scholar
  80. Vitiello B (2006) An update on publicly funded multisite trials in pediatric psychopharmacology. Child Adolesc Psychiatr Clin N Am 15:1–12PubMedCrossRefGoogle Scholar
  81. Vitiello B, Jensen PJ (1997) Medication development and testing in children and adolescents. Arch Gen Psychiatry 54:871–876PubMedGoogle Scholar
  82. Vitiello B, Riddle MA, Greenhill LL, March JS, Levine J, Schachar R, Abikoff H, Zito J, McCracken J, Walkup J, Findling RL, Robinson J, Cooper T, Davies M, Varipatis E, Labellarte M, Scahill L, Capasso L (2003) How can we improve the assessment of safety in child and adolescent psychopharmacology? J Am Acad Child Adolesc Psychiatry 42:634–641CrossRefPubMedGoogle Scholar
  83. Vitiello B, Heiligenstein JH, Riddle MA, Greenhill LL, Fegert JM (2004) The interface between publicly funded and industry-funded research in pediatric psychopharmacology: opportunities for integration and collaboration. Biol Psychiatry 56:3–9CrossRefPubMedGoogle Scholar
  84. Vitiello B, Zuvekas S, Norquist DG (2006) National estimates of antidepressant medication use among U.S. children in 1997–2002. J Am Acad Child Adolesc Psychiatry 45:271–279CrossRefPubMedGoogle Scholar
  85. Wagner KD, Ambrosini P, Rynn M, Wohlberg C, Yang R, Greenbaum MS et al (2003) Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA 290:1033–1041CrossRefPubMedGoogle Scholar
  86. Wagner KD, Robb AS, Findling RL, Jin J, Gutierrez MM, Heydorn WE (2004) A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents. Am J Psychiatry 161:1079–1083CrossRefPubMedGoogle Scholar
  87. Werry JS, Aman MG (1999) Practitioner’s guide to psychoactive drugs for children and adolescents. Plenum Publishing, New York, NYGoogle Scholar
  88. Weissman MM, Wolk S, Goldstein RB, Moreau D, Adams P, Greenwald S, Klier CM, Ryan ND, Dahl RE, Wickramaratne P (1999) Depressed adolescents grow up. JAMA 281:1707–1713CrossRefPubMedGoogle Scholar
  89. Whittington CJ, Kendall T, Fonagy, Cottrell D, Cotgrove A, Boddington E (2004) Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet 363:1341–1345CrossRefPubMedGoogle Scholar
  90. Wilens TE, Cohen L, Biederman J, Abrams A, Neft D, Faird N, Sinha V (2002) Fluoxetine pharmacokinetics in pediatric patients. J Clin Psychopharmacol 22:568–575CrossRefPubMedGoogle Scholar
  91. Wilens TE, Faraone SV, Biederman J, Gunawardene S (2003) Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics 111:179–185CrossRefPubMedGoogle Scholar
  92. Zerhouni E (2005) US biomedical research: basic, translational, and clinical sciences. JAMA 294:1352–1358CrossRefPubMedGoogle Scholar
  93. Zito JM, Safer DJ, DosReis S, Gardner JF, Magder L, Soeken K, Boles M, Lynch F, Riddle MA (2003) Psychotropic practice patterns for youth: a 10-year perspective. Arch Pediatr Adolesc Med 157:17–25PubMedGoogle Scholar
  94. Zuvekas SH, Vitiello B, Norquist NS (2006) Recent trends in stimulant medication use among U.S. children. Am J Psychiatry 163:579–585CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Chief, Child and Adolescent Treatment and Preventive Intervention Research BranchNational Institute of Mental HealthBethesdaUSA

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