Advertisement
Advances in Pediatrics

Controversies Surrounding Pediatric Psychopharmacology

      The past several decades have witnessed an increased awareness of mental health disorders and neurobehavioral problems in children [
      • Merikangas K.R.
      • He Jp
      • Burstein M.
      • et al.
      Lifetime prevalence of mental disorders in US adolescents: results from the National Comorbidity Survey Replication (NCS-A).
      ]. These behavioral issues now represent a growing portion of pediatric visits. Addressing and appropriately managing early-onset disorders may improve quality of life while providing hope that adult morbidity may be attenuated [
      • Arango C.
      • Parellada M.
      • Moreno D.M.
      Clinical effectiveness of new generation antipsychotics in adolescent patients.
      ]. Given the shortage of mental health providers and the concept of the pediatric practice as “medical home,” many pediatricians are poised to receive this population. Caring for this population of children is riddled with systemic obstacles. Lack of time, training, support, and compensation, together with poor integration of collaboration with mental health resources, all contribute to this challenge. Children’s mental health has become a priority issue for the American Academy of Pediatrics [
      • Foy J.M.
      • Duncan P.
      • Frankowski B.
      • American Academy of Pediatrics Task Force on Mental Health
      • et al.
      Enhancing pediatric mental health care: report from the American Academy of Pediatrics Task Force on Mental Health. Introduction.
      ].
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Advances in Pediatrics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Merikangas K.R.
        • He Jp
        • Burstein M.
        • et al.
        Lifetime prevalence of mental disorders in US adolescents: results from the National Comorbidity Survey Replication (NCS-A).
        J Am Acad Child Adolesc Psychiatry. 2010; 49: 980-989
        • Arango C.
        • Parellada M.
        • Moreno D.M.
        Clinical effectiveness of new generation antipsychotics in adolescent patients.
        Eur Neuropsychopharmacol. 2004; 14: 471-479
        • Foy J.M.
        • Duncan P.
        • Frankowski B.
        • American Academy of Pediatrics Task Force on Mental Health
        • et al.
        Enhancing pediatric mental health care: report from the American Academy of Pediatrics Task Force on Mental Health. Introduction.
        Pediatrics. 2010; 125: S69-S74
        • Coleman W.L.
        • Dobbins M.I.
        • Garner A.S.
        • Committee on Psychosocial Aspects of Child and Family Health and Task Force on Mental Health
        • et al.
        The future of pediatrics: mental health competencies for pediatric primary care.
        Pediatrics. 2009; 124: 410-421
        • Brown R.T.
        • Freeman W.S.
        • Perrin J.M.
        • et al.
        Prevalence and assessment of attention-deficit/hyperactivity disorder in primary care settings.
        Pediatrics. 2000; 107: e43
        • Costello E.J.
        • Angold A.
        • Burns J.
        • et al.
        The great smoky mountains study of youth. goals, design, methods, and the prevalence of DSM-III-R disorders.
        Arch Gen Psychiatry. 1996; 53: 1129-1136
        • Rice C.
        • et al.
        Prevalence of autism spectrum disorders—autism and developmental disabilities monitoring network, United States, 2006.
        Mobid Mortal Week Rep. 2009; 58: 1-20
        • Cavagnaro A.T.
        Autistic spectrum disorders: changes in the California caseload, an update June 1987-June 2007: California Health and Human Services Agency. State of California 2003 survey of developmental disabilities.
        (Available at:) (Accessed December 5, 2011)
        • Radley D.C.
        • Finkelstein S.N.
        • Stafford R.S.
        Off-label prescribing among office-based physicians.
        Arch Intern Med. 2006; 166 ([psychiatric drugs]): 1021-1026
        • Zito J.M.
        • Derivan A.T.
        • Kratochvil C.J.
        • et al.
        Off-label psychopharmacologic prescribing for children: history supports close clinical monitoring.
        Child Adolesc Psychiatry Ment Health. 2008; 2: 24
        • Cooper W.O.
        • Hickson G.B.
        • Fuchs D.C.
        • et al.
        New users of antipsychotic medication among children enrolled in TennCare.
        Arch Pediatr Adolesc Med. 2004; 158: 753-759
        • Cascade E.
        • Kalali A.
        • Findling R.
        Use of antipsychotics in children.
        Psychiatry (Edgmont). 2009; 6: 21-23
        • Patel N.C.
        • Sanchez R.J.
        • Johnsrud M.T.
        • et al.
        Trends in antipsychotic use in a Texas Medicaid population of children and adolescents: 1996 to 2000.
        J Child Adolesc Psychopharmacol. 2002; 12: 221-229
        • Cooper W.O.
        • Arbogast P.G.
        • Ding H.
        • et al.
        Trends in prescribing of antipsychotic medications for US children.
        Ambul Pediatr. 2006; 6: 79-83
      1. (Available at:) (Accessed December 5, 2011)
        • Walkup J.T.
        • Albano A.M.
        • Piacentini J.
        • et al.
        Cognitive-behavioral therapy, sertraline and their combination for children and adolescents with anxiety disorders: acute phase efficacy and safety.
        N Engl J Med. 2008; 359: 2753-2766
        • Franklin M.
        • Foa E.
        • March J.
        Pediatric obsessive-compulsive disorder treatment Study.
        J Am Acad Child Adolesc Psychiatry. 2004; 292: 1969-1976
        • Foy J.M.
        • Perrin J.
        • American Academy of Pediatrics Task Force on Mental Health
        Enhancing pediatric mental health care: strategies for preparing a community.
        Pediatrics. 2010; 125: S75-S86
        • Eaton D.K.
        • Kann L.
        • Kinchen S.A.
        • et al.
        Youth risk behavior surveillance—United States, 2005.
        MMWR Surveill Summ. 2006; 55: 1-108
        • March J.
        • Silva S.
        • Curry J.
        • et al.
        Treatment for adolescents with Depression Study (TADS): long-term effectiveness and safety.
        Arch Gen Psychiatry. 2007; 64: 1132-1143
      2. The MTA Cooperative Group: a 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder.
        Arch Gen Psychiatry. 1999; 56: 1073-1086
        • American Academy of Pediatrics. Subcommittee on Attention-Deficit/Hyperactivity Disorder and Committee on Quality Improvement
        Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder.
        Pediatrics. 2001; 108: 1033-1044
        • Pliszka S.
        • AACAP Work Group
        Practice parameters for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder.
        J Am Acad Child Adolesc Psychiatry. 2007; 46: 894-921
        • Oswald D.P.
        • Sonenklar N.A.
        Medication use among children with autism spectrum disorders.
        J Child Adolesc Psychopharmacol. 2007; l17: 348-355
      3. (Available at:) (Study Accessed December 5, 2011)
        • Preskorn S.H.
        Clinically relevant pharmacology of selective serotonin reuptake inhibitors: an overview with emphasis on drug metabolism.
        Clinical Pharmacokinet. 1997; 32: 1-21
        • DeVane C.L.
        Pharmacokinetics of the selective serotonin reuptake inhibitors.
        J Clin Psychiatry. 1992; 53: 13-20
        • Leslie L.K.
        • Newman T.B.
        • Chesney P.J.
        • et al.
        The Food and Drug Administration’s deliberations on antidepressants use in pediatric patients.
        Pediatrics. 2005; 116: 195-201
        • Khan A.
        • Khan S.
        • Kolts R.
        • et al.
        Suicide rates in clinical trials of SSRIs other antidepressants and placebo: analysis of FDA reports.
        Am J Psychiatry. 2003; 160: 790-792
        • Hammad T.A.
        • Laughren T.
        • Racoosin J.
        Suicidality in pediatric patients treated with antidepressant drugs.
        Arch Gen Psychiatry. 2006; 63: 332-339
        • Jick H.
        • Kaye J.
        • Jick S.
        Antidepressants and the risk of suicidal behaviors.
        JAMA. 2004; 292: 338-343
      4. American College of Neuropsychopharmacology, preliminary report of the task force on SSRI’s and suicidal behavior in youth.
        (Available at:)
        www.ancp.org
        Date: 2004
        (Accessed December 5, 2011)
      5. U.S. FDA Public Health Advisory: suicidality in children and adolescents being treated with antidepressant medications; 2004.

        • Olfson M.
        • Shaffer D.
        • Marcus S.
        • et al.
        Relationship between antidepressant medication treatment and suicide in adolescents.
        Arch Gen Psychiatry. 2003; 60: 978-982
        • Gibbons R.D.
        • Brown H.
        • Hur K.
        • et al.
        Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents.
        Am J Psychiatry. 2007; 164: 1356-1363
        • Mamdani M.M.
        Health advisories: when good intentions go bad.
        CMAJ. 2008; 178: 1025-1026
        • Katz Ly
        • Kozyrskyj A.L.
        • Prior H.J.
        • et al.
        Effects of regulatory warnings on antidepressant prescribing rates, use of health services and outcomes among children, adolescents and young adults.
        CMAJ. 2008; 178: 1005-1011
        • Birmaher B.
        • Brent D.
        • Bernet W.
        • et al.
        Practice parameter for the assessment and treatment of children and adolescents with depressive disorders.
        J Am Acad Child Adolesc Psychiatry. 2007; 46: 1503-1536
        • Boyer E.W.
        • Shannon M.
        The serotonin syndrome.
        N Engl J Med. 2005; 352: 1112-1120
        • Birmes P.
        • Coppin D.
        • Schmitt L.
        • et al.
        Serotonin syndrome: a brief review.
        CMAJ. 2003; 168: 1439-1442
        • Coupland N.J.
        • Bell C.J.
        • Potokar J.P.
        Serotonin reuptake inhibitor withdrawal.
        J Clin Psychopharmacol. 1996; 16: 356-362
        • Moses-Kolko E.L.
        • Bogen D.
        • Perel J.
        • et al.
        Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications.
        JAMA. 2005; 293: 2372-2383
        • Laine k
        • Heikkinen T.
        • Ekblad U.
        • et al.
        Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations.
        Arch Gen Psychiatry. 2003; 60: 720-726
        • Nordeng H.
        • Lindemann R.
        • Perminov A.
        Neonatal withdrawal syndrome after in utero exposure to serotonin reuptake inhibitors.
        Acta Paediatr. 2001; 90: 288-291
        • Chambers C.D.
        • Hernandez-Diaz S.
        • Van Marter L.J.
        • et al.
        Selective serotonin reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn.
        N Engl J Med. 2006; 354: 579-587
        • Williams K.
        • Wheeler D.M.
        • Silove N.
        • et al.
        Selective serotonin reuptake inhibitors (SSRI) for autism spectrum disorders (ASD).
        Cochrane Database Syst Rev. 2010; 8 (CD004677)
        • King B.H.
        • Hollander E.
        • Sikich L.
        • et al.
        (STAART Psychopharmacology Network): lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism.
        Arch Gen Psychiatry. 2009; 66: 583-590
        • Bradley C.
        The behavior of children receiving benzedrine.
        Am J Psychiatry. 1937; 94: 577-585
        • Spencer T.
        • Biederman J.
        • Harding M.
        • et al.
        Growth deficits in ADHD children revisited: evidence for disorder-associated growth delays?.
        J Am Acad Child Adolesc Psychiatry. 1996; 35: 1460-1469
        • Swanson J.M.
        • Elliott G.R.
        • Greenhill L.L.
        • et al.
        Effects of stimulant medication on growth rates across 3 years in the MTA follow-up.
        J Am Acad Child Adolesc Psychiatry. 2007; 46: 1015-1027
        • Swanson J.M.
        • Hinshaw S.P.
        • Arnold L.E.
        • et al.
        Secondary evaluations of MTA 36-month outcomes: propensity score and growth mixture model analyses.
        J Am Acad Child Adolesc Psychiatry. 2007; 46: 1002-1013
        • Biederman J.
        • Spencer T.J.
        • Monuteaux M.C.
        • et al.
        A naturalistic 10-year prospective study of height and weight in children with attention-deficit hyperactivity disorder grown up: sex and treatment effects.
        J Pediatr. 2010; 157 (e1): 635-640
        • Zhang H.
        • Du H.
        • Zhuang H.
        Impact of long-term treatment of methylphenidate on height and weight of school age children with ADHD.
        Neuropediatrics. 2010; 41: 55-59
        • Bloch M.H.
        • Panza K.E.
        • Landeros-Weisenberger A.
        • et al.
        Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders.
        J Am Acad Child Adolesc Psychiatry. 2009; 48: 884-893
        • Riddle M.A.
        • Lynch K.A.
        • Scahill L.
        • et al.
        Effects of methylphenidate discontinuation and reinitiation in children with Tourette’s syndrome and ADHD.
        J Child Adolesc Psychopharmacol. 1995; 5: 205
        • Law S.F.
        • Schachar R.J.
        Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder?.
        J Am Acad Child Adolesc Psychiatry. 1999; 38: 944-951
        • Gadow K.D.
        • Sverd J.
        • Sprafkin J.
        • et al.
        Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder.
        Arch Gen Psychiatry. 1995; 52: 444-455
        • Gadow K.D.
        • Sverd J.
        • Sprafkin J.
        • et al.
        Long term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder.
        Arch Gen Psychiatry. 1999; 56: 330-336
        • Poncin Y.
        • Sukhodolsky D.G.
        • McGuire J.
        • et al.
        Drug and non-drug treatments of children with ADHD and tic disorders.
        Eur Child Adolesc Psychiatry. 2007; 16: 78-88
        • The Tourette’s Syndrome Study Group
        Treatment of ADHD in children with tics: a randomized controlled trial.
        Neurology. 2002; 58: 527-536
        • Greenhill L.L.
        • Findling R.L.
        • Swanson J.M.
        • ADHD Study Group
        A double-blind, placebo-controlled study of modified-release methylphenidate in children with attention-deficit/hyperactivity disorder.
        Pediatrics. 2002; 109: e39
        • Wigal S.B.
        • Wilens T.E.
        • Wolraich M.
        • et al.
        Hematologic and blood biochemistry monitoring during methylphenidate treatment in children with attention-deficit/hyperactivity disorder: 2-year, open-label study results.
        Pediatrics. 2007; 120: e120-e128
      6. U.S. Food and Drug Administration (2005) public health advisory for Adderall and Adderall XR.
        (Available at:) (Accessed January 24, 2006)
        • Rosack J.
        US regulators puzzled by Canada’s ruling on safety of ADHD drug.
        Psychiatr News. 2005; 40: 5-9
      7. Adderall XR [package insert]. Wayne, PA: Shire US Inc; 2010.

      8. Concerta [package insert]. Titusville, NJ: McNeil Pediatrics; 2008.

      9. Focalin XR [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2008.

        • Vetter V.L.
        • Elia J.
        • Erickson C.
        • et al.
        A scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing.
        Circulation. 2008; 117: 2407-2423
        • Warren A.E.
        • Hamilton R.M.
        • Belanger S.A.
        • et al.
        Cardiac risk assessment before the use of stimulant medications in children and youth: a joint position statement by the Canadian Paediatric Society, the Canadian Cardiovascular Society, and the Canadian Academy of Child and Adolescent Psychiatry.
        Can J Cardiol. 2009; 25: 625-630
        • Wigal S.B.
        • Jun A.
        • Wong A.
        Does prior exposure to stimulants in children with ADHD impact cardiovascular parameters from lisdexamfetamine dimesylate?.
        Postgrad Med. 2010; 122: 27-34
        • Perrin J.M.
        • Friedman R.A.
        • Knilans T.K.
        Cardiovascular monitoring and stimulant drugs for attention deficit hyperactivity disorder.
        Pediatrics. 2008; 122: 451-453
        • Wilens T.E.
        • Faraone S.V.
        • Biederman J.
        • et al.
        Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? a meta-analytic review of the literature.
        Pediatrics. 2003; 111: 179-185
        • Mannuzza S.
        • Klein R.G.
        • Truong N.L.
        • et al.
        Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood.
        Am J Psychiatry. 2008; 165: 604-609
        • Biederman J.
        • Monuteaux M.C.
        • Spencer T.
        • et al.
        Stimulant therapy and risk for subsequent substance use disorders in male adults with ADHD: a naturalistic controlled 10-year follow-up study.
        Am J Psychiatry. 2008; 165: 597-603
        • Disney E.R.
        • Elkins I.J.
        • McGue M.
        • et al.
        Effects of ADHD, conduct disorder, and gender on substance use and abuse in adolescence.
        Am J Psychiatry. 1999; 156: 1515-1521
        • Molina B.S.G.
        • Flory K.
        • Hinshaw S.P.
        • et al.
        Delinquent behavior and emerging substance use in the MTA at 36 months: prevalence, course, and treatment effects.
        J Am Acad Child Adolesc Psychiatry. 2007; 46: 1028-1040
        • Wigal S.B.
        • Gupta S.
        • Greenhill L.
        • et al.
        Pharmacokinetics of methylphenidate in preschoolers with attention-deficit/hyperactivity disorder.
        J Child Adolesc Psychopharmacol. 2007; 17: 153-164
        • Wigal T.
        • Wigal S.
        • Shanklin A.
        • et al.
        ADHD in preschoolers: a diagnosis—or just a “PhAse”?.
        Consultant for Pediatricians. 2008; 8: S2-S8
        • Faraone S.V.
        • Beiderman J.
        • Spencer T.J.
        Comparing the efficacy of medications for ADHD using meta-analysis.
        Medscape General Medicine. 2006; 8: 4
        • Donnelly C.
        • Bangs M.
        • Trzepacz P.
        • et al.
        Safety and tolerability of atomoxetine over 3 to 4 years in children and adolescents with ADHD.
        J Am Acad Child Adolesc Psychiatry. 2009; 48: 176-185
        • Loo S.
        • Barkley R.
        Clinical utility of EEG in attention deficit hyperactivity disorder.
        Appl Neuropsychol. 2005; 12: 64-76
        • Gevensleben H.
        • Holl B.
        • Albrecht B.
        • et al.
        Neurofeedback training in children with ADHD: 6-month follow-up of a randomized controlled trial.
        Eur Child Adolesc Psychiatry. 2010; 19: 715-724
        • Gevensleben H.
        • Holl B.
        • Albrecht B.
        • et al.
        Is neurofeedback an efficacious treatment for ADHD? A randomized controlled clinical trial.
        J Child Psychol Psychiatry. 2009; 50: 780-789
        • Patel N.C.
        • Crismon M.L.
        • Hoagwood K.
        • et al.
        Trends in the use of typical and atypical antipsychotics in children and adolescents.
        J Am Acad Child Adolesc Psychiatry. 2005; 44: 548-556
        • Olfson M.
        • Blanco C.
        • Liu L.
        • et al.
        National trends in the outpatient treatment of children and adolescents with antipsychotic drugs.
        Arch Gen Psychiatry. 2006; 63: 679-685
        • Vitiello B.
        • Correll C.
        • van Zwieten-Boot B.
        • et al.
        Antipsychotics in children and adolescents: increasing use, evidence for efficacy and safety concerns.
        Eur Neuropsychopharmacol. 2009; 19: 629-635
        • Weiss M.
        • Panagiotopoulos C.
        • Giles L.
        • et al.
        A naturalistic study of predictors and risks of atypical antipsychotic use in an attention-deficit/hyperactivity disorder clinic.
        J Child Adolesc Psychopharmacol. 2009; 19: 575-582
        • Kumar R.
        • Perminder S.
        Akathesia and second generation antipsychotic drugs.
        Curr Opin Psychiatry. 2009; 22: 293-299
        • Cooper B.M.
        • Keck P.E.
        • Satlin A.
        • et al.
        Prevalence and severity of akathisia in patients on clozapine.
        Biol Psychiatry. 1991; 29: 1215-1219
        • Shirazadi A.A.
        • Ghaemi S.N.
        Side effects of atypical antipsychotics: extrapyramidal symptoms and the metabolic syndrome.
        Harv Rev Psychiatry. 2006; 14: 152-164
        • Findling R.L.
        Paediatric psychopharmacology: closing the gap between science and practice.
        Expert Opin Pharmacother. 2001; 2: 523-525
        • Laita P.
        • Cifuentes A.
        • Doll A.
        • et al.
        Antipsychotic-related abnormal involuntary movements and metabolic and endocrine side effects in children and adolescents.
        J Child Adolesc Psychopharmacol. 2007; 17: 487-502
        • Correll C.U.
        • Carlson H.E.
        Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents.
        J Am Acad Child Adolesc Psychiatry. 2006; 45: 771-791
        • Correll C.U.
        Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents.
        J Clin Psychiatry. 2008; 69: 26-30
        • Correll C.U.
        • Manu P.
        • Olshanskiy V.
        • et al.
        Cardiometabolic risk of second generation antipsychotic medications during first time use in child and adolescents.
        JAMA. 2009; 302: 1765-1773
        • Kumra S.
        • Oberstar J.V.
        • Sikich L.
        • et al.
        Efficacy and tolerabilityof second-generation antipsychotics in children and adolescent with schizophrenia.
        Schizophr Bull. 2008; 34: 60-71
        • Shaw P.
        • Sporn A.
        • Gogtay N.
        • et al.
        Childhood-onset schizophrenia: a double-blind, randomized clozapine-olanzapine comparison.
        Arch Gen Psychiatry. 2006; 63: 721-730
        • Lieberman J.A.
        • Stroup T.S.
        • McEvoy J.P.
        • et al.
        (Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators): effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
        N Engl J Med. 2005; 353: 1209-1223
        • Sikich L.
        • Frazier J.A.
        • McClellan J.
        • et al.
        Double blind comparison of first- and second-generation antipsychotics in early onset schizophrenia: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.
        Am J Psychiatry. 2008; 165: 1420-1431
        • McCracken J.T.
        • Mcgough J.
        • Shah B.
        Risperidone in children with autism and serious behavior problems.
        N Engl J Med. 2002; 347: 314-321
        • Haupt D.W.
        • Rosenblatt L.C.
        • Kim E.
        • et al.
        Prevalence and predictors of lipid and glucose monitoring in commercially insured patients treated with second-generation antipsychotic agents.
        Am J Psychiatry. 2009; 166: 345
        • Correll C.U.
        Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes.
        J Am Acad Child Adolesc Psychiatry. 2008; 47: 9-20
        • Foy J.M.
        • Kelleher K.J.
        • Laraque D.
        • American Academy of Pediatrics Task Force on Mental Health
        • et al.
        Enhancing pediatric mental health care: strategies for preparing a primary care practice.
        Pediatrics. 2010; 125: S87-S108