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DOI: 10.1055/s-0042-117644
Pharmacotherapy in Psychiatric Disorders of Children: Current Evidence and Trends
Publication History
received 24 June 2016
revised 08 September 2016
accepted 09 September 2016
Publication Date:
13 October 2016 (online)
![](https://www.thieme-connect.de/media/pharmaco/201606/lookinside/thumbnails/2016-06-0587_10-1055-s-0042-117644-1.jpg)
Abstract
Pharmacotherapeutic interventions are available for most psychiatric disorders in children. Evidence for these interventions varies, depending on the targeted disorders. For attention-deficit/hyperactivity disorder, a sound database on efficacy and safety of medication exists. For other common disorders or psychopathological phenomena like disruptive behavior, anxiety disorders, depressive disorders, or autism, data on efficacy and safety are much scarcer. This selective review aims to provide an overview about current psychopharmacological interventions in child and adolescent psychiatry. The literature indicates either a lower efficacy than other interventions or less beneficial effects compared to possible adverse events in these cases. Most guidelines recommend psychopharmacotherapy in children to be embedded in a psychosocial or therapeutic intervention plan. Decision for medication depends on the severity of symptoms, chronicity, and, most important, impairment of the child in academic performance, family relationships, and everyday life. The high rates of off-label use in the age group of children are often due to a lack of market authorization studies less indicative of low efficacy. As adverse events need to be monitored closely, pharmacotherapy should mainly be restricted to experienced mental health care providers.
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References
- 1 Koelch M, Schnoor K, Fegert JM. Ethical issues in psychopharmacology of children and adolescents. Curr Opin in Psychiatry 2008; 21: 598-605
- 2 Persico AM, Arango C, Buitelaar JK. et al. Unmet needs in paediatric psychopharmacology: present scenario and future perspectives. Eur Neuropsychopharmacol 2015; 25: 1513-1531
- 3 Kölch M, Allroggen M, Fegert JM. Off-label use in child and adolescent psychiatry. An ongoing ethical, medical and legal problem. Nervenarzt 2009; 80: 789-796
- 4 Gerlach M, Warnke A. Medikamentöse Behandlung in der Kinder- und Jugendpsychiatrie in Deutschland zwischen ethischen sowie sozial-und haftungsrechtlichen Konflikten. Z Kinder und Jugendpsychiatr Psychother 2016; 44: 249-255
- 5 Kölch M, Ludolph AG, Plener PL. et al. Safeguarding children’s rights in psychopharmacological research: ethical and legal issues. Curr Pharm Des 2010; 16: 2398-2406
- 6 Banaschewski T, Coghill D, Santosh P. et al. Long-acting medications for the hyperkinetic disorders: a systematic review and European treatment guideline. Eur Child Adolesc Psychiatry 2006; 15: 476-495
- 7 Plener PL, Fegert JM, Kölch MG. Psychopharmakologische Behandlung von Depressionen im Kindes- und Jugendalter, Entwicklungen und Standards seit der «Black Box» Warnung. Z Kinder Jugendpsychiatr Psychother 2012; 40: 365-371
- 8 Hazell P, Mirzaie M. Tricyclic drugs for depression in children and adolescents. Cochrane Database Syst Rev 2013; 6: CD002317
- 9 Franke C, Fegert JM, Krüger U et al. Verordnungshäufigkeiten von Psychopharmaka bei Kindern und Jugendlichen mit psychischen Erkrankungen in Deutschland. Z Kinder Jugendpsychiatr Psychother 2016 [Epub ahead of print]
- 10 Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie, P.u.P.2013 15.02.2016. Accessed at http://www.awmf.org/leitlinien/detail/ll/028-043.html
- 11 National Institute for Health and Clinical Excellence. Depression in children and young people: identification and management. 2005; Accessed at http://www.nice.org.uk/CG28
- 12 Bolea-Alamañac B, Nutt DJ, Adamou M. et al. Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: update on recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2014; 28: 179-203
- 13 Graham J, Banaschewski T, Buitelaar J. et al. European guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry 2011; 20: 17-37
- 14 Hinshaw SP, Arnold LE. MTA Cooperative Group . Attention-deficit hyperactivity disorder, multimodal treatment, and longitudinal outcome: evidence, paradox, and challenge. Wiley Interdiscip Rev Cogn Sci 2015; 6: 39-52
- 15 Vitiello B, Elliott GR, Swanson JM. et al. Blood pressure and heart rate over 10 years in the multimodal treatment study of children with ADHD. Am J Psychiatry 2012; 169: 167-177
- 16 Storebø OJ, Simonsen E, Gluud C. Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents. JAMA 2016; 315: 2009-2010
- 17 Faraone SV, Buitelaar J. Comparing the efficacy of stimulants for ADHD in children and adolescents using meta-analysis. Eur Child Adolesc Psychiatry 2010; 19: 353-364
- 18 Schwartz S, Correll CU. Efficacy and safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: results from a comprehensive meta-analysis and metaregression. J Am Acad Child Adolesc Psychiatry 2014; 53: 174-187
- 19 Hirota T, Schwartz S, Correll CU. Alpha-2 agonists for attention-deficit/hyperactivity disorder in youth: a systematic review and meta-analysis of monotherapy and add-on trials to stimulant therapy. J Am Acad Child Adolesc Psychiatry 2014; 53: 153-173
- 20 Huss M, Chen W, Ludolph AG. Guanfacine extended release: a new pharmacological treatment option in Europe. Clin Drug Investig 2016; 36: 1-25
- 21 Sonuga-Barke EJ, Brandeis D, Cortese S. et al. Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments. Am J Psychiatry 2013; 170: 275-289
- 22 Daley D, van der Oord S, Ferrin M. et al. Behavioral interventions in attention-deficit/hyperactivity disorder: a meta-analysis of randomized controlled trials across multiple outcome domains. J Am Acad Child Adolesc Psychiatry 2014; 53: 835-847
- 23 Chirdkiatgumchai V, Xiao H, Fredstrom BK. et al. National trends in psychotropic medication use in young children: 1994–2009. Pediatrics 2013; 132: 615-623
- 24 Boland F, Galvin R, Reulbach U. et al. Psychostimulant prescribing trends in a paediatric population in Ireland: a national cohort study. BMC Pediatr 2015; 15: 118
- 25 Garbe E, Mikolajczyk RT, Banaschewski T. et al. Drug treatment patterns of attention-deficit/hyperactivity disorder in children and adolescents in Germany: results from a large population-based cohort study. J Child Adolesc Psychopharmacol 2012; 22: 452-458
- 26 Kölch MG, Prestel A, Singer H. et al. Psychotropic medication in children and adolescents in Germany: prevalence, indications, and psychopathological patterns. J Child Adolesc Psychopharmacol 2009; 19: 765-770
- 27 Posner K, Melvin GA, Murray DW. et al. Clinical presentation of attention-deficit/hyperactivity disorder in preschool children: the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS). J Child Adolesc Psychopharmacol 2007; 17: 547-562
- 28 Riddle MA, Yershova K, Lazzaretto D. et al. The preschool attention-deficit/hyperactivity disorder treatment study (PATS) 6-year follow-up. J Am Acad Child Adolesc Psychiatry 2013; 52: 264-278
- 29 Vitiello B, Lazzaretto D, Yershova K. et al. Pharmacotherapy of the Preschool ADHD Treatment Study (PATS) children growing up. J Am Acad Child Adolesc Psychiatry 2015; 54: 550-556
- 30 Plener PL, Witt A, Straub J. et al. Disruptive Mood Dysregulation Disorder (DMDD) als neues Störungsbild im DSM-5. Kinder- und Jugendmedizin 2013; 5: 354-361
- 31 Pappadopulos E, Rosato NS, Correll CU. et al. Experts’ recommendations for treating maladaptive aggression in youth. J Child Adolesc Psychopharmacol 2011; 21: 505-515
- 32 Connor DF, Glatt SJ, Lopez ID. et al. Psychopharmacology and aggression. I: Ameta-analysis of stimulant effects on overt/covert aggression-related behaviors in ADHD. J Am Acad Child Adolesc Psychiatry 2002; 41: 253-261
- 33 Pappadopulos E, Woolston S, Chait A. et al. Pharmacotherapy of aggression in children and adolescents: efficacy and effect size. J Can Acad Child Adolesc Psychiatry 2006; 15: 27-39
- 34 Scahill L, Chappell PB, Kim YS. et al. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry 2001; 158: 1067-1074
- 35 Jaselskis C, Cook EH, Fletcher KE. et al. Clonidine treatment of hyperactive and impulsive children with autistic disorder. J Clin Psychopharmacol 1992; 12: 322-327
- 36 Werry JS, Aman MG, Lampen E. Haloperidol and methylphenidate in hyperactive children. Acta Paedopsychiatrica 1975; 42: 26-40
- 37 Campbell M, Perry R, Green WH. et al. Behavioral efficacy of haloperidol and lithium carbonate: a comparison in hospitalized aggressive children with conduct disorder. Arch Gen Psychiat 1984; 41: 650-656
- 38 Calarge CA, Murry DJ, Ziegler EE et al. Serum ferritin, weight gain, disruptive behavior, and extrapyramidal symptoms in risperidonetreated youth. J Child Adolesc Psychopharmacol 2016 [Epub ahead of print]
- 39 Malone RP, Delaney MA, Luebbert JF. et al. A double-blind placebo-controlled study of lithium in hospitalized aggressive children and adolescents with conduct disorder. Arch Gen Psychiatry 2000; 57: 649-654
- 40 Posey DJ, Erickson CA, McDougle CJ. Developing drugs for core social and communication impairment in autism. Child Adolesc Psychiatr Clin N Am 2008; 17: 787-801
- 41 Minshawi NF, Wink LK, Shaffer R. et al. A randomized, placebo-controlled trial of d-cycloserine for the enhancement of social skills training in autism spectrum disorders. Mol Autism 2016; 7: 2
- 42 Freitag CM, Jarczok TA. Autismus-Spektrum-Störungen. In Gerlach M, Mehler-Wex C, Walitza S. et al. (eds.). Neuro-/Psychopharmaka im Kindes- und Jugendalter. 3rd ed. Berlin, Heidelberg: Springer; 2016
- 43 Wink LK, Erickson CA, McDougle CJ. Pharmacologic treatment of behavioral symptoms associated with autism and other pervasive developmental disorders. Curr Treat Options Neurol 2010; 12: 529-538
- 44 McQuire C, Hassiotis A, Harrison B. et al. Pharmacological interventions for challenging behaviour in children with intellectual disabilities: a systematic review and meta-analysis. BMC Psychiatry 2015; 26: 303
- 45 Croonenberghs J, Fegert JM, Findling RL. et al. Risperidone in children with disruptive behavior disorders and subaverage intelligence: a 1-year, open-label study of 504 patients. J Am Acad Child Adolesc Psychiatry 2005; 44: 64-72
- 46 Reyes M, Croonenberghs J, Augustyns I. et al. Long-term use of risperidone in children withdisruptive behavior disorders and subaverage intelligence: efficacy, safety, and tolerability. J Child Adolesc Psychopharmacol 2006; 16: 260-272
- 47 Hässler F, Dück A, Jung M. et al. Treatment of aggressive behavior problems in boys with intellectual disabilities using zuclopenthixol. J Child Adolesc Psychopharmacol 2014; 24: 579-581
- 48 Treatment for Adolescents with Depression Study Team . Treatment for Adolescents With Depression Study (TADS): rationale, design, and methods. J Am Acad Child Adolesc Psychiatry 2003; 42: 531-542
- 49 Goodyer I, Dubicka B, Wilkinson P. et al. Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behavior therapy in adolescents with major depression: Randomised controlled trial. BMJ 2007; 335: 142-150
- 50 Birmaher B, Brent D. AACAP Work Group on Quality Issues . et al. Practice parameters for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child and Adolesc Psychiatry 2007; 46: 1503-1526
- 51 Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006; 63: 332-339
- 52 Cox GR, Callahan P, Churchill R. et al. Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents. Cochrane Database Syst Rev 2014; 11 CD008324
- 53 Katz LY, Kozyrskyj AL, Prior HJ. et al. Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults. CMAJ 2008; 178: 1005-1011
- 54 Strawn JR, Adler CM, McNamara RK. et al. Antidepressant tolerability in anxious and depressed youth at high risk for bipolar disorder: a prospective naturalistic treatment study. Bipolar Disord 2014; 16: 523-530
- 55 Amitai M, Chen A, Weizmann A. et al. SSRI-induced activation syndrome in children and adolescents – what is next?. Curr Treatm Opt Psychiat 2015; 2: 28-37
- 56 Gibbons RD, Brown CH, Hur K. et al. Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Arch Gen Psychiatry 2012; 69: 580-587
- 57 Sharma T, Guski LS, Freund N et al. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ 2016 [Epub ahead of print]
- 58 Safer DJ, Zito JM. Treatment-emergent adverse events from selective Serotonin reuptake inhibitors by age group: children versus adolescents. J Child Adolesc Psychopharmacol 2006; 16: 159-169
- 59 Ma D, Zhang Z, Zhang X. et al. Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: a multiple-treatments meta-analysis. Curr Med Res Opin 2014; 30: 971-995
- 60 Hoffmann F, Glaeske G, Petermann F. et al. Outpatient treatment in German adolescents with depression: an analysis of nationwide health insurance data. Pharmacoepidemiol Drug Saf 2012; 21: 972-979
- 61 Bloch MH, Storch EA. Assessment and management of treatment-refractory obsessive-compulsive disorder in children. J Am Acad Child Adolesc Psychiatry 2015; 54: 251-262
- 62 Ivarsson T, Skarphedinsson G, Kornør H. et al. The place of and evidence for serotonin reuptake inhibitors (SRIs) for obsessive compulsive disorder (OCD) in children and adolescents: views based on a systematic review and meta-analysis. Psychiatry Res 2015; 227: 93-103
- 63 McGuire JF, Piacentini J, Lewin AB. et al. A metanalysis of cognitive behavior therapy and medication for child obsessive-compulsive disorder: moderators of treatment efficacy, response and remission. Depress Anxiety 2015; 32: 580-593
- 64 Skarphedinsson G, Weidel B, Ivarsson T. Sertraline treatment of nonresponders to extended cognitive-behavior therapy in pedicatric obsessive-compulsive disorder. J Child Adolesc Psychopharmacol 2015; 25: 549-579
- 65 Ak M, Bulut SD, Bozkurt A. et al. Aripiprazole augmentation of Serotonin Reuptake Inhibitors in treatment-resistant obsessive-compulsive disorder: a 10-week open-label study. Adv Ther 2011; 28: 341-348
- 66 Ercan ES, Ardic UA, Ercan E. et al. A promising preliminary study of Aripiprazole for treatment-resistant childhood obsessive-compulsive disorder. J Child Adolesc Psychopharmacol 2015; 25: 580-584
- 67 Kendall PC, Cummings CM, Villabø MA. et al. Mediators of change in the Child/Adolescent Anxiety Multimodal Treatment Study. J Consult Clin Psychol 2016; 84: 1-14
- 68 Wehry AM, Beesdo-Baum K, Hennelly MM. et al. Assessment and treatment of anxiety disorders in children and adolescents. Curr Psychiatry Rep 2015; 17: 52
- 69 Kaakeh Y, Stumpf JL. Treatment of selective mutism: focus on selective serotonin reuptake inhibitors. Pharmacother 2008; 28: 214-224
- 70 Black B, Uhde TW. Treatment of elective mutism with fluoxetine: a double-blind, placebo-controlled study. J Am Acad Child Adolesc Psychiatry 1994; 33: 1000-1006
- 71 Dummit ES, Klein RG, Tancer NK. et al. Fluoxetine treatment of children with selective mutism: an open trial. J Am Acad Child Adolesc Psychiatry 1996; 35: 615-621
- 72 Manassis K, Tannock R. Comparing interventions for selective mutism: a pilot study. Can J Psychiatry 2008; 53: 700-703
- 73 Bachmann CJ, Lempp T, Glaeske G. et al. Antipsychotic prescription in children and adolescents. Dtsche Arztebl Int 2014; 111: 25-34
- 74 Bennett K, Teeling M, Feely J. Overprescribing antidepressants to children: pharmacoepidemiological study in primary care. BMJ 2005; 331: 1451-1452
- 75 Fegert JM, Kölch M, Zito JM. et al. Antidepressant use in children and adolescents in Germany. J Child and Adolesc Psychopharmacol 2006; 16: 197-206
- 76 Volkers AC, Heerdink ER, van Dijk L. Antidepressant use and off-label prescribing in children and adolescents in Dutch general practice (2001–2005). Pharmacoepidemiol Drug Saf 2007; 16: 1054-1062
- 77 Zito JM, Tobi H, de Jong-van den Berg LT. et al. Antidepressant prevalence for youths: a multi-national comparison. Pharmacoepidemiol Drug Saf 2006; 15: 793-798
- 78 Bachmann CJ, Aagaard L, Burcu M. et al. Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005–2012. Eur Neuropsychopharmacol 2016; 26: 411-419
- 79 Libby AM, Brent DA, Morrato EH. et al. Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs. Am J Psychiatry 2007; 164: 884-891
- 80 Nemeroff CB, Kalali A, Keller MB. et al. Impact of publicity concerning pediatric suicidality data on physician practice patterns in the United States. Arch Gen Psychiat 2007; 64: 466-472
- 81 Olfson M, Marcus SC, Druss B. Effects of food and drug administration warnings on antidepressant use in a national sample. Arch Gen Psychiat 2008; 65: 94-101
- 82 Chorozoglou M, Smith E, Koerting J. et al. Preschool hyperactivity is associated with long-term economic burden: evidence from a longitudinal health economic analysis of costs incurred across childhood, adolescence and young adulthood. J Child Psychol Psychiatry 2015; 56: 966-975
- 83 Patton GC, Coffey C, Romaniuk H. et al. The prognosis of common mental disorders in adolescents: a 14-year prospective cohort study. Lancet 2014; 383: 1404-1411
- 84 Brent DA, Emslie G, Clarke G. et al. Switching to another SSRI or to venlafaxine with or without cognitive behavioural therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. J Am Med Assoc 2008; 299: 901-913
- 85 Inglis SK, Carucci S, Garas P. et al. Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study. BMJ Open 2016; 6: e010433
- 86 Egberts K, Karwautz A, Plener PL. et al. Pharmakovigilanz in der Kinder- und Jugendpsychiatrie. Z Kinder Jugendpsychiat 2015; 43: 21-28