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Cited by 44Attention Deficit Hyperactivity DisorderPharmaceutical studies and practicesChild and Adolescent Psychosocial and Emotional Development

Pediatric psychopharmacology: Too much or too little?

Open access
Rapoport, Judith L.·2013·World Psychiatry
DOI 10.1002/wps.20028PMC PMC3683256
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Abstract

This paper provides a selective overview of the past, present and future of pediatric psychopharmacology. The acceptance of medication use in child psychiatry was based on the results of double-blind, placebo-controlled trials documenting the efficacy of drug treatments for attention-deficit/hyperactivity disorder, enuresis, depression, anxiety disorders, obsessive-compulsive disorder and psychoses. This period of success was followed by a series of challenges, including a growing awareness of the long-term adverse effects of medications and of the inadequacy of long-term drug surveillance. There is great concern today that children are being overtreated with medication, especially in the US. Further advances in pediatric psychopharmacology may come from examination of large medical data sets including both pharmacological and psychiatric information, which could lead to drug repurposing, as well as from preclinical translational studies such as those using human induced pluripotent stem cells. Copyright © 2013 World Psychiatric Association.

Integrity signals

Registry

Crossref · 10.1002/wps.20028

Cites

81 of 81 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

23 of 80 cited sources checked · 8 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Later studies extended antidepressant treatment to pediatric anxiety disorders.

    “Later studies extended antidepressant treatment to pediatric anxiety disorders (21,22).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [21] 21. Klein RG, Koplewicz HS, Kanner A. Imipr- amine treatment of children with separa- tion anxiety disorder. J Am Acad Child Adolesc Psychiatry 1992;31:21-8. source
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  • Premisecitation

    Some behavioral dyscontrol with chronic irritability in fact did predict depression in later life.

    “The answer was complex, as some behavioral dyscontrol with chronic irritability in fact did predict depression in later life (17,18)”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [17] 17. Copeland WE, Shanahan L, Costello EJ et al. Childhood and adolescent psychiat- ric disorders as predictors of young adult disorders. Arch Gen Psychiatry 2009;66: 764-72. source
    • cites [18] 18. Stringaris A, Cohen P, Pine DS et al. Adult outcomes of youth irritability: a 20- year prospective community-based study. Am J Psychiatry 2009;166:1048-54. source
  • Premisecitation

    First-generation antipsychotics carry a high risk for tardive dyskinesia following long-term use.

    “First-generation antipsychotics carry a high risk for tardive dyskinesia following long-term use (44).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [44] 44. Campbell M, Rapoport JL, Simpson GM. Antipsychotics in children and adoles- cents. J Am Acad Child Adolesc Psychia- try 1999;38:537-45. source

      The Long-Term Untoward Effects section calls tardive and withdrawal dyskinesias the most common long-term adverse effects of antipsychotics and reports dyskinesias in 12%–33.9% of children treated long term. Those figures combine tardive and withdrawal dyskinesias; the paper says withdrawal dyskinesia is more frequent, so it does not establish that the risk of tardive dyskinesia alone is high across first-generation antipsychotics. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    The duration of stimulant drug treatment has also greatly increased.

    “The duration of stimulant drug treatment has also greatly increased (34)(35)(36).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [34] 34. Zito JM, Safer DJ, de Jong-van den Berg LT et al. A three-country comparison of psychotropic medication prevalence in youth. Child Adolesc Psychiatry Ment Health 2008;2:26. source

      The Methods (Measures; page unavailable) define annual prescription prevalence, while the Results (Concomitant psychotropic patterns; page unavailable) compare co-prescription across observation windows. Neither reports a historical increase in the duration of stimulant treatment; searches for treatment duration and longer-term stimulant use found no supporting passage. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [35] 35. Zito JM, Safer DJ. Recent child pharma- coepidemiological findings. J Child Ado- lesc Psychopharmacol 2005;15:5-9. source
    • cites [36] 36. Zito JM. Pharmacoepidemiology: recent findings and challenges for child and ado- lescent psychopharmacology. J Clin Psy- chiatry 2007;68:966-7. source
  • Premisecitation

    The rates of increase of pediatric psychotropic drug prescription in the US are alarming.

    “The rates of increase of pediatric psychotropic drug prescription in the US are alarming (30,34).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [30] 30. Findling RL, McNamara NK, Gracious BL. Paediatric uses of atypical antipsy- chotics. Expert Opin Pharmacother 2000; 1:935-45. source
    • cites [34] 34. Zito JM, Safer DJ, de Jong-van den Berg LT et al. A three-country comparison of psychotropic medication prevalence in youth. Child Adolesc Psychiatry Ment Health 2008;2:26. source

      The Background reports that psychotropic medication use among youth increased during the preceding decade in the US and other countries. But the Limitations state that this study's one-year, cross-sectional data cannot establish rates of increase, and the paper does not characterize the US increase as alarming. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 11
  • May combine two claims. 22

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Studies of childhood onset obsessive-compulsive disorder led to the development of specialty clinics for these children in several countries and to the recognition of the close association of this disorder with Tourette's disorder.

    “Studies of childhood onset obsessive-compulsive disorder (25) led to the development of specialty clinics for these children in several countries and to the recognition of the close association of this disorder with Tourette's disorder (26).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [25] 25. Flament MF, Rapoport JL, Berg CJ et al. Clomipramine treatment of childhood obsessive-compulsive disorder. A double- blind controlled study. Arch Gen Psychi- atry 1985;42:977-83. source
    • cites [26] 26. Lenane MC, Swedo SE, Leonard H et al. Psychiatric disorders in first degree rela- tives of children and adolescents with obsessive compulsive disorder. J Am Acad Child Adolesc Psychiatry 1990;29: 407- 12. source

  • May combine two claims.

    Premisecitation

    The period of success of pediatric psychopharmacology was followed by challenges including growing awareness of long-term adverse effects of medications and inadequacy of long-term drug surveillance.

    “This period of success was followed by a series of challenges, including a growing awareness of the long-term adverse effects of medications and of the inadequacy of long-term drug surveillance.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [44] 44. Campbell M, Rapoport JL, Simpson GM. Antipsychotics in children and adoles- cents. J Am Acad Child Adolesc Psychia- try 1999;38:537-45. source

      The Long-Term Untoward Effects section identifies dyskinesias as major long-term limitations of antipsychotics in children, and Long-Term Studies notes that only two long-term placebo-controlled studies had been conducted. The paper supports concern about adverse effects and limited long-term evidence, but it does not describe a period of success followed by these challenges or specifically assess long-term drug surveillance. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [45] 45. Correll CU, Manu P, Olshanskiy V et al. Cardiometabolic risk of second-genera- tion antipsychotic medications during first-time use in children and adolescents. JAMA 2009;302:1765-73. source

      The Discussion (page unavailable) reports rapid cardiometabolic changes in antipsychotic-naïve youth and calls for more frequent monitoring, citing suboptimal metabolic monitoring. It does not describe a historical period of success followed by challenges, establish long-term medication adverse effects, or assess the adequacy of long-term drug surveillance. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [55] 55. Meyer RE, Salzman C, Youngstrom EA et al. Suicidality and risk of suicide -defi- nition, drug safety concerns, and a neces- sary target for drug development: a con- sensus statement. J Clin Psychiatry 2010; 71:e1-21. source

  • May combine two claims.

    Premisecitation

    Post-mortem human brain studies may ultimately generate new targets, as gene expression studies of post-mortem brains in autism have implicated pathways for both brain development and immune responses.

    “Post-mortem human brain studies may ultimately generate new targets, as gene expression studies of post-mortem brains in autism have implicated pathways for both brain development and immune responses (67).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [67] 67. Voineagu I, Wang X, Johnston P et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 2011;474:380-4. source

  • May combine two claims.

    Premisecitation

    The use of low-dose antipsychotic medications is widespread in child psychiatry for conduct disorders, as augmentation of SSRIs for pediatric obsessive-compulsive disorder, and for Tourette's disorder and motor tic disorders.

    “The use of low-dose antipsychotic medications is widespread in child psychiatry for conduct disorders, as augmentation of SSRIs for pediatric obsessive-compulsive disorder, and for Tourette's disorder and motor tic disorders (29).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [29] 29. Findling RL, Horwitz SM, Birmaher B et al. Clinical characteristics of children receiving antipsychotic medication. J Child Adolesc Psychopharmacol 2011; 21:311-9. source

      The Introduction reports increasing antipsychotic prescribing in children, and the Discussion suggests that some prescriptions may address disruptive behavior symptoms. But the Discussion says prescriptions were not associated with a disruptive behavior diagnosis. The paper does not establish widespread low-dose use for conduct disorders, SSRI augmentation in pediatric OCD, or Tourette’s and tic disorders. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The DSM-5 is going to place emphasis on psychopathological dimensions, and this may be a useful step forward.

    “The DSM-5 is going to place emphasis on psychopathological dimensions, and this may be a useful step forward (72).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [72] 72. Insel T, Cuthbert B, Garvey M et al. Research Domain Criteria (RDoC): to- ward a new classification framework for research on mental disorders. Am J Psy- chiatry 2010;167:748-51. source

      The RDoC discussion (Am J Psychiatry 167:7, July 2010; page not specified in our copy) advocates studying the full range of psychopathological dimensions and suggests this could help identify intervention thresholds. It does not say that DSM-5 is going to emphasize those dimensions; its dimensional proposal concerns RDoC research. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Using Rett syndrome as a model, neurons derived from human induced pluripotent stem cells from people with the syndrome have been found to have fewer synapses and some electrophysiological defects.

    “Using Rett syndrome as a model, neurons derived from human induced pluripotent stem cells from people with the syndrome have been found to have fewer synapses and some electrophysiological defects (76).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [76] 76. Brennand KJ, Simone A, Tran N et al. Modeling psychiatric disorders at the cel- lular and network levels. Mol Psychiatry 2012;17:1239-53. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Antipsychotics have been a mainstay of treatment for childhood, adolescent and adult onset psychosis.

    “Antipsychotics have been a mainstay of treatment for childhood, adolescent and adult onset psychosis (29).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] 29. Findling RL, Horwitz SM, Birmaher B et al. Clinical characteristics of children receiving antipsychotic medication. J Child Adolesc Psychopharmacol 2011; 21:311-9. source

      The Clinical Significance section says children with psychotic disorders were among those most likely to be prescribed antipsychotics; the DSM-IV psychiatric disorders and symptoms section reports that 9 of 13 children with a psychotic disorder received one. This supports use in children with psychotic disorders, but the paper does not establish that antipsychotics are a treatment mainstay for childhood, adolescent, and adult-onset psychosis. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The Research Domain Criteria project involves measurement of common physiological, neuropsychological, or brain imaging markers to identify a patient subgroup or alternately be themselves a target for treatment.

    “The Research Domain Criteria project (73,74) involves measurement of common physiological, neuropsychological, or brain imaging markers to identify a patient subgroup or alternately be themselves a target for treatment.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [73] 73. Craske MG. The R-DoC initiative: sci- ence and practice. Depress Anxiety 2012; 29:253-6.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [74] 74. Greenwood TA, Lazzeroni LC, Murray SS et al. Analysis of 94 candidate genes and 12 endophenotypes for schizophre- nia from the Consortium on the Genetics of Schizophrenia. Am J Psychiatry 2011; 168:930-46. source

      The Introduction (page unavailable) describes measuring neurophysiological and neurocognitive endophenotypes and proposes that genes associated with them may serve as biomarkers for early identification and as treatment targets. It does not describe the Research Domain Criteria project or brain-imaging markers, and its proposed treatment targets are genes rather than the measured markers themselves. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Only recently sizeable multimodal normative brain developmental data have become available, with large prospective studies ongoing in Rotterdam, San Diego and Philadelphia.

    “The tools that we have for measuring brain functioning and connectivity are growing, but only recently sizeable multimodal normative brain developmental data have become available, with large prospective studies ongoing in Rotterdam (68), San Diego (69) and Philadelphia (70).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [68] 68. Jaddoe VW, van Duijn CM, van der Heij- den AJ et al. The Generation R Study: design and cohort update 2010. Eur J Epidemiol 2010;25:823-41. source

      The Study design > Overview and Study area sections identify Generation R as a prospective cohort in Rotterdam, and the postnatal assessments section reports brain ultrasound in a subgroup. But Measurements from the age of 5 years says detailed MRI studies were still being discussed and tested; this copy does not establish that sizeable multimodal normative brain data had already become available from the Rotterdam study. Page numbers are not provided in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [69] 69. Gur RC, Richard J, Calkins ME et al. Age group and sex differences in performance on a computerized neurocognitive battery in children age 8-21. Neuropsychology 2012; 26:251-65. source
    • cites [70] 70. Sanislow CA, Pine DS, Quinn KJ et al. Developing constructs for psychopathol- ogy research: Research Domain Criteria. J Abnorm Psychol 2010;119:631-9. source

      The Neurodevelopment section discusses the importance of developmental information for psychopathology research, but does not describe sizeable multimodal normative brain datasets or prospective studies in Rotterdam, San Diego, or Philadelphia. Searches for those locations and for multimodal normative developmental data found no supporting passage in our copy. (LLM, conf=0.73)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Atypical antipsychotics, originally thought safer because of decreased risk of tardive dyskinesia, are now known to be at increased risk for cardiometabolic syndrome, particularly in adolescents.

    “Originally thought safer because of decreased risk of tardive dyskinesia, these drugs are now known to be at increased risk for cardiometabolic syndrome, particularly in adolescents (45).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [45] 45. Correll CU, Manu P, Olshanskiy V et al. Cardiometabolic risk of second-genera- tion antipsychotic medications during first-time use in children and adolescents. JAMA 2009;302:1765-73. source

      The Introduction and Discussion report cardiometabolic risks of second-generation antipsychotics in children and adolescents, including substantial weight gain and metabolic changes. But the Results say metabolic syndrome developed in only 1.6% during the short study, and the paper does not establish that adolescents are at greater risk than other age groups. Our copy also does not address the claimed historical rationale about reduced tardive dyskinesia. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S4 (based).

    Premisereasoning

    Because non-medical therapists are less costly, psychiatrists in most insurance plans have been assigned exclusively to medication clinics.

    “Because non-medical therapists are less costly, psychiatrists in most insurance plans have been assigned exclusively to medication clinics.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Such children did respond to treatment, although effect sizes varied widely across studies.

    “and such children did respond to treatment (19,20), although effect sizes varied widely across studies.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] 19. Kovacs M, Feinberg TL, Crouse-Novak MA et al. Depressive disorders in child- hood. I. A longitudinal prospective study of characteristics and recovery. Arch Gen Psychiatry 1984;41:229-37. source
    • cites [20] 20. Rush AJ, Kovacs M, Beck AT et al. Differ- ential effects of cognitive therapy and pharmacotherapy on depressive symp- toms. J Affect Disord 1981;3:221-9. source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisereasoning

    With the transition to managed care in the US, medication has shifted to more of a business model.

    “With the transition to managed care in the US, medication has shifted to more of a business model.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Antidepressant treatments were initially studied in children with enuresis, but later extended to children with depression and anxiety disorders.

    “Antidepressant treatments were initially studied in children with enuresis (13), but later extended to children with depression and anxiety disorders (14).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [13] 13. Mikkelsen EJ, Rapoport JL. Enuresis: psychopathology, sleep stage, and drug response. Urol Clin North Am 1980;7: 361-77. source
    • cites [14] 14. Puig-Antich JP, Perel JM, Chambers WJ. Imipramine treatment of prepubertal ma- jor depressive disorders: plasma levels and clinical response -preliminary report. Psy- chopharmacol Bull 1980;16: 25-7.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    These are now drug treatments of documented efficacy for pediatric generalized anxiety disorder, separation anxiety, social anxiety and panic disorder.

    “These are now drug treatments of documented efficacy for pediatric generalized anxiety disorder, separation anxiety, social anxiety and panic disorder (23,24).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [23] 23. de Beurs E, van Balkom AJ, Lange A et al. Treatment of panic disorder with agora- phobia: comparison of fluvoxamine, pla- cebo, and psychological panic manage- ment combined with exposure and of ex- posure in vivo alone. Am J Psychiatry 1995;152:683-91. source
    • cites [24] 24. Ballenger JC. Remission rates in patients with anxiety disorders treated with parox- etine. J Clin Psychiatry 2004;65:1696-707. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Double-blind, placebo-controlled drug treatment trials required assembly of large numbers of children, and the recognition that obsessive-compulsive disorder could best be diagnosed and assessed using the child as informant.

    “Again, doubleblind, placebo-controlled drug treatment trials required assembly of large numbers of children, and the recognition that obsessive-compulsive disorder could best be diagnosed and assessed using the child as informant (27).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] 27. Swedo SE, Leonard HL, Rapoport JL. Childhood-onset obsessive compulsive dis- order. Psychiatr Clin North Am 1992;15: 767-75. source

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    The acceptance of drug treatment in child psychiatry has often been uncritical, including a drastic increase in polypharmacy.

    “The acceptance of drug treatment has been often uncritical, including a drastic increase in polypharmacy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Most of our drugs still act on the monoaminergic and glutaminergic targets that have been known for decades.

    “Finally, there is the awareness that most of our drugs still act on the monoaminergic and glutaminergic targets that have been known for decades.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Long-term prospective follow-up studies of children with documented ADHD have showed that a substantial group of patients continue to have significant symptoms, with only about 40% truly remitting.

    “Long-term prospective follow-up studies of children with documented ADHD have showed that a substantial group of patients continue to have significant symptoms, with only about 40% truly remitting (10,11).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] 10. Hechtman L, Weiss G, Finklestein J et al. Hyperactives as young adults: prelimi- nary report. Can Med Assoc J 1976;115: 625-30.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [11] 11. Mannuzza S, Klein RG, Bonagura N et al. Hyperactive boys almost grown up. II. Status of subjects without a mental disorder. Arch Gen Psychiatry 1988;45: 13-8. source

  • May combine two claims.

    Interpretationnone given

    Looking back, it is apparent that there was over-acceptance of drug treatment, leading to reductionist biology.

    “Looking back, it is apparent that there was over-acceptance of drug treatment, leading to reductionist biology.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Genetic-based animal models of autism, ADHD, obsessive-compulsive disorder and schizophrenia have generated putative candidates, but this has not led to successful clinical trials.

    “Genetic-based animal models of autism, ADHD, obsessive-compulsive disorder and schizophrenia have generated putative candidates, but this has not led to successful clinical trials.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    While short-term administration of stimulants with drug holidays did not have a long-term influence on height, the more sustained and longer use of these drugs has raised this issue once more.

    “While short-term administration of stimulants with drug holidays did not have a long-term influence on height, the more sustained and longer use of these drugs has raised this issue once more (41).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] 41. Swanson J, Greenhill L, Wigal T et al. Stimulant-related reductions of growth rates in the PATS. J Am Acad Child Ado- lesc Psychiatry 2006;45:1304-13. source

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    New treatments remain unfortunately remote.

    “There are now imaginative new approaches to psychiatric diagnosis (such as the Research Domain Criteria project) and astonishing preclinical translational studies (such as the study of human induced pluripotent stem cells), but new treatments remain unfortunately remote.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Current medications are only partially successful, with 40-50% of patients having incomplete response and/or intolerance.
    • Rests on an assumption: The complexity of the search for new targets has made many pharmaceutical companies leave the field.

  • May combine two claims.

    Interpretationreasoning

    The FDA action both reflected and fueled public suspicion and backlash against pediatric psychopharmacology.

    “The FDA action both reflected and fueled public suspicion and backlash against pediatric psychopharmacology.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Collectively, these cases are far more common than those of childhood psychoses, and the problems of obesity and the cardiometabolic syndrome are even more alarming.

    “Collectively, these cases are far more common than those of childhood psychoses, and the problems of obesity and the cardiometabolic syndrome are even more alarming.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: In children with drug-related obesity, weight loss occurs slowly and incompletely when the drug is stopped.

  • May combine two claims.

    Premisecitation

    Results of double-blind trials of SSRIs have been more compelling in adolescents, but the effect sizes vary widely, with possibly better responses with fluoxetine.

    “Results of double-blind trials of SSRIs have been more compelling in adolescents ( 51), but the effect sizes vary widely, with possibly better responses with fluoxetine (52).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [51] 51. Pine DS. Treating children and adoles- cents with selective serotonin reuptake inhibitors: how long is appropriate? J Child Adolesc Psychopharmacol 2002; 12:189-203. source
    • cites [52] 52. Bridge JA, Iyengar S, Salary CB et al. Clini- cal response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA 2007;297:1683-96. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Everyone involved in this issue agreed that current post-marketing surveillance of drugs is inadequate.

    “Part of the issue was the failure to distinguish between suicidality and actual self-harm, but everyone involved in this issue agreed that current post-marketing surveillance of drugs is inadequate (55).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] 55. Meyer RE, Salzman C, Youngstrom EA et al. Suicidality and risk of suicide -defi- nition, drug safety concerns, and a neces- sary target for drug development: a con- sensus statement. J Clin Psychiatry 2010; 71:e1-21. source

  • May combine two claims.

    Premisecitation

    Clozapine is the most effective (and toxic) of all antipsychotics for childhood psychosis.

    “These medications remain of major importance, including clozapine, the most effective (and toxic) of all for childhood psychosis (46,47).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [46] 46. Kumra S, Frazier JA, Jacobsen LK et al. Childhood-onset schizophrenia. A dou- ble-blind clozapine-haloperidol compari- son. Arch Gen Psychiatry 1996;53:1090- 7. source
    • cites [47] 47. Shaw P, Sporn A, Gogtay N et al. Child- hood-onset schizophrenia: a double-blind, randomized clozapine-olanzapine compar- ison. Arch Gen Psychiatry 2006; 63:721-30. source
28 of 28

  • The paper relies on this without support.

    Current medications are only partially successful, with 40-50% of patients having incomplete response and/or intolerance.

    “As our current medications are only partially successful, with 40-50% of patients having incomplete response and/or intolerance, the field still has a great deal to accomplish.”

  • The paper relies on this without support.

    The complexity of the search for new targets has made many pharmaceutical companies leave the field.

    “Yet, the complexity of the search for new targets has made many pharmaceutical companies leave the field.”

  • The paper relies on this without support.

    ADHD did not respond well to traditional psychotherapy.

    “The clear and immediate benefits for the child and the family were particularly welcome as ADHD did not respond well to traditional psychotherapy.”

  • The paper relies on this without support.

    In children with drug-related obesity, weight loss occurs slowly and incompletely when the drug is stopped.

    “One of the most disturbing aspects of drug-related obesity in children is that weight loss occurs slowly and incompletely when the drug is stopped.”
4 of 4

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Authors
Rapoport, J. L.
Affiliations
National Institute of Mental Health (US)
Corresponding author
Rapoport, Judith L.
Venue
World Psychiatry
Publisher
Wiley
Published
2013-06
Volume
12
Issue
2
Pages
118-123
ISSN
  • 1723-8617 (ISSN-L)
  • 2051-5545
DOI
10.1002/wps.20028
PMC
PMC3683256
OpenAlex
W2067562167
Cited by
44
References
77
Citations by year
2026: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 5 · 2018: 1 · 2016: 10 · 2015: 5 · 2014: 9 · 2013: 2
FWCI
4.81
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3 d)
Locations
  • World Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion)
  • PubMed Central (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
Keywords
pediatric psychopharmacology, child psychiatry, attention deficit hyperactivity disorder, enuresis, childhood depression, childhood anxiety disorders, obsessive-compulsive disorder, pharmacovigilance

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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