The current state-of-the-art in pharmacotherapy for pediatric generalized anxiety disorder

References

• Ezpeleta L, Keeler G, Erkanli A, et al. Epidemiology of psychiatric disability in childhood and adolescence. J Child Psychol Psychiat Allied Discipline. 2001;42(7):901–914. DOI:10.1111/1469-7610.00786
   PubMed Web of Science ®Google Scholar
• Costello EJ, Mustillo S, Erkanli A, et al. Prevalence and development of psychiatric disorders in childhood and adolescence. Arch Gen Psychiatry. 2003;60(8):837–844. DOI:10.1001/archpsyc.60.8.837
   PubMed Web of Science ®Google Scholar
• Costello EJ, Copeland W, Angold A. Trends in psychopathology across the adolescent years: what changes when children become adolescents, and when adolescents become adults? J Child Psychol Psychiatry. 2011;52(10):1015–1025.
   PubMed Web of Science ®Google Scholar
• Merikangas KR, He J-P, Burstein M, et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication–Adolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry. 2010;49(10):980–989. DOI:10.1016/j.jaac.2010.05.017
   PubMed Web of Science ®Google Scholar
• Kendall PC, Safford S, Flannery-Schroeder E, et al. Child anxiety treatment: outcomes in adolescence and impact on substance use and depression at 7.4-year follow-up. J Consult Clin Psychol. 2004;72(2):276. DOI:10.1037/0022-006X.72.2.276
   PubMed Web of Science ®Google Scholar
• Treffers P, Silverman W. Anxiety and its disorders in children and adolescents before the twentieth century. In: Silverman W, Treffers P, editors. Anxiety Disorders in Children and Adolescents: Research, Assessment and Intervention (Cambridge Child and Adolescent Psychiatry). Cambridge: Cambridge University Press; 2000. p.1–22. DOI:10.1017/CBO9780511663239.002
   Google Scholar
• Consortium WWMHS. Prevalence, severity, and unmet need for treatment of mental disorders in the. World Health Organ World Mental Health Surv Jama. 2004;291(21):2581–2590.
   Google Scholar
• Essau CA, Conradt J, Petermann F. Frequency, comorbidity, and psychosocial impairment of anxiety disorders in German adolescents. J Anxiety Disord. 2000;14(3):263–279.
   PubMed Web of Science ®Google Scholar
• Strauss CC, Frame CL, Forehand R. Psychosocial impairment associated with anxiety in children. J Clin Child Psychol. 1987;16(3):235–239.
   Web of Science ®Google Scholar
• Kessler RC, Avenevoli S, Costello J, et al. Severity of 12-month DSM-IV disorders in the national comorbidity survey replication adolescent supplement. Arch Gen Psychiatry. 2012;69(4):381–389. DOI:10.1001/archgenpsychiatry.2011.1603
   PubMed Web of Science ®Google Scholar
• American Psychiatric Association A, Association AP. Diagnostic and statistical manual of mental disorders: dSM-5. Vol. 10. (WA) DC: American psychiatric association; 2013.
   Google Scholar
• Pine DS, Cohen P, Gurley D, et al. The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders. Arch Gen Psychiatry. 1998;55(1):56–64. DOI:10.1001/archpsyc.55.1.56
   PubMed Web of Science ®Google Scholar
• Beesdo K, Pine DS, Lieb R, et al. Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder. Arch Gen Psychiatry. 2010;67(1):47–57. DOI:10.1001/archgenpsychiatry.2009.177
   PubMed Web of Science ®Google Scholar
• Woodward LJ, Fergusson DM. Life course outcomes of young people with anxiety disorders in adolescence. J Am Acad Child Adolesc Psychiatry. 2001;40(9):1086–1093.
   PubMed Web of Science ®Google Scholar
• Husky MM, Olfson M, He J-P, et al. Twelve-month suicidal symptoms and use of services among adolescents: results from the National Comorbidity Survey. Psychiatric Serv. 2012;63(10):989–996. DOI:10.1176/appi.ps.201200058
   PubMed Web of Science ®Google Scholar
• Foley DL, Goldston DB, Costello EJ, et al. Proximal psychiatric risk factors for suicidality in youth: the great smoky mountains study. Arch Gen Psychiatry. 2006;63(9):1017–1024. DOI:10.1001/archpsyc.63.9.1017
   PubMed Web of Science ®Google Scholar
• Barrett PM, Fox T, Farrell LJ. Parent—child interactions with anxious children and with their siblings: an observational study. Behav Change. 2005;22(4):220–235.
   Web of Science ®Google Scholar
• Hudson JL, Rapee RM. Parent–child interactions and anxiety disorders: an observational study. Behav Res Ther. 2001;39(12):1411–1427.
   PubMed Web of Science ®Google Scholar
• Culpepper L, Conner K. Effective recognition and treatment of generalized anxiety disorder in primary care. Prim Care Companion J Clin Psychiatry. 2004;6:35–41.
   PubMedGoogle Scholar
• Piacentini J, Roblek T. Recognizing and treating childhood anxiety disorders: these disorders are treatable but often are neglected by practitioners. West J Emergency Med. 2002;176(3):149.
   Google Scholar
• Hettema JM, Neale MC, Kendler KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry. 2001;158(10):1568–1578.
   PubMed Web of Science ®Google Scholar
• Kendall PC, Hudson JL, Gosch E, et al. Cognitive-behavioral therapy for anxiety disordered youth: a randomized clinical trial evaluating child and family modalities. J Consult Clin Psychol. 2008;76(2):282–297. DOI:10.1037/0022-006X.76.2.282
   PubMed Web of Science ®Google Scholar
• Walkup JT, Albano AM, Piacentini J, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med. 2008;359(26):2753–2766. DOI:10.1056/NEJMoa0804633
   PubMed Web of Science ®Google Scholar
• Borquist-Conlon DS, Maynard BR, Brendel KE, et al. Mindfulness-based interventions for youth with anxiety: a systematic review and meta-analysis. Res Social Work Pract. 2019;29(2):195–205. DOI:10.1177/1049731516684961
   Google Scholar
• Strawn JR, Welge JA, Wehry AM, et al. Efficacy and tolerability of antidepressants in pediatric anxiety disorders: a systematic review and meta‐analysis. Depress Anxiety. 2015;32(3):149–157. DOI:10.1002/da.22329
   PubMed Web of Science ®Google Scholar
• Strawn JR, Geracioti L, Rajdev N, et al. Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert Opin Pharmacother. 2018;19(10):1057–1070. DOI:10.1080/14656566.2018.1491966
   PubMed Web of Science ®Google Scholar
• Kendall PC, Compton SN, Walkup JT, et al. Clinical characteristics of anxiety disordered youth. J Anxiety Disord. 2010;24(3):360–365. DOI:10.1016/j.janxdis.2010.01.009
   PubMed Web of Science ®Google Scholar
• Compton SN, Walkup JT, Albano AM, et al. Child/Adolescent anxiety multimodal study (CAMS): rationale, design, and methods. Child Adolesc Psychiatry Ment Health. 2010;4(1):1–15. DOI:10.1186/1753-2000-4-1
   PubMedGoogle Scholar
• Mochcovitch MD, da Rocha Freire RC, Garcia RF, et al. A systematic review of fMRI studies in generalized anxiety disorder: evaluating its neural and cognitive basis. J Affective Disorders. 2014;167:336–342.
   PubMed Web of Science ®Google Scholar
• Strawn JR, Wehry AM, DelBello MP, et al. Establishing the neurobiologic basis of treatment in children and adolescents with generalized anxiety disorder. Depress Anxiety. 2012;29(4):328–339. DOI:10.1002/da.21913
   PubMed Web of Science ®Google Scholar
• Blackford JU, Pine DS. Neural substrates of childhood anxiety disorders: a review of neuroimaging findings. Child and Adolescent Psychiatric Clinics. 2012;21(3):501–525.
   PubMedGoogle Scholar
• Ho TC. Toward neurobiological-based treatments of depression and anxiety: a potential case for the nucleus accumbens. J Am Acad Child Adolesc Psychiatry. 2022;61(2):136–138.
   PubMedGoogle Scholar
• Piacentini J, Bennett S, Compton SN, et al. 24-and 36-week outcomes for the Child/Adolescent Anxiety Multimodal Study (CAMS). J Am Acad Child Adolesc Psychiatry. 2014;53(3):297–310. DOI:10.1016/j.jaac.2013.11.010
   PubMed Web of Science ®Google Scholar
• Strawn JR, Sakolsky DJ, Rynn MA. Psychopharmacologic treatment of children and adolescents with anxiety disorders. Child and Adolescent Psychiatric Clinics. 2012;21(3):527–539.
   PubMedGoogle Scholar
• Naveed S, Amray AN, Jahan N, et al. Psychopharmacology in pediatric mixed anxiety disorder: an evidence-based review. Innov Clin Neurosci. 2019;16(9–10):36–43.
   PubMedGoogle Scholar
• Graae F, Milner J, Rizzotto L, et al. Clonazepam in childhood anxiety disorders. J Am Acad Child Adolesc Psychiatry. 1994;33(3):372–376. DOI:10.1097/00004583-199403000-00011
   PubMed Web of Science ®Google Scholar
• Coşkun M, Öztürk M, Zoroğlu S. Escitalopram treatment in preschool children with anxiety disorders: a case series. Klinik Psikofarmakoloji Bülteni-Bulletin of Clin Psychopharmacol. 2012;22(3):262–267.
   Web of Science ®Google Scholar
• Van Ameringen M, Mancini C, Patterson B, et al. Symptom relapse following switch from Celexa to generic citalopram: an anxiety disorders case series. J Psychopharmacol. 2007;21(5):472–476. DOI:10.1177/0269881107077373
   PubMedGoogle Scholar
• Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
   PubMed Web of Science ®Google Scholar
• Walkup JT, Labellarte MJ, Riddle MA, et al. Fluvoxamine for the treatment of anxiety disorders in children and adolescents. N Engl J Med. 2001;344(17):1279–1285. DOI:10.1056/NEJM200104263441703
   PubMed Web of Science ®Google Scholar
• Walkup JT, Labellarte MJ, Riddle MA, et al. Treatment of pediatric anxiety disorders: an open-label extension of the research units on pediatric psychopharmacology anxiety study. J Child Adolesc Psychopharmacol. 2002;12(3):175–188.
   PubMed Web of Science ®Google Scholar
• Abikoff H, McGough J, Vitiello B, et al. Sequential pharmacotherapy for children with comorbid attention-deficit/hyperactivity and anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2005;44(5):418–427. DOI:10.1097/01.chi.0000155320.52322.37
   PubMedGoogle Scholar
• Fairbanks JM, Pine DS, Tancer NK, et al. Open fluoxetine treatment of mixed anxiety disorders in children and adolescents. J Child Adolesc Psychopharmacol. 1997;7(1):17–29. DOI:10.1089/cap.1997.7.17
   PubMed Web of Science ®Google Scholar
• Birmaher B, Axelson DA, Monk K, et al. Fluoxetine for the treatment of childhood anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2003;42(4):415–423. DOI:10.1097/01.CHI.0000037049.04952.9F
   PubMed Web of Science ®Google Scholar
• Clark DB, Birmaher B, Axelson D, et al. Fluoxetine for the treatment of childhood anxiety disorders: open-label, long-term extension to a controlled trial. J Am Acad Child Adolesc Psychiatry. 2005;44(12):1263–1270. DOI:10.1097/01.chi.0000183464.41777.c1
   PubMed Web of Science ®Google Scholar
• Maslowsky J, Mogg K, Bradley BP, et al. A preliminary investigation of neural correlates of treatment in adolescents with generalized anxiety disorder. J Child Adolesc Psychopharmacol. 2010;20(2):105–111. DOI:10.1089/cap.2009.0049
   PubMedGoogle Scholar
• da Costa CZG, de Morais RMCB, Zanetta DMT, et al. Comparison among clomipramine, fluoxetine, and placebo for the treatment of anxiety disorders in children and adolescents. J Child Adolesc Psychopharmacol. 2013;23(10):687–692. DOI:10.1089/cap.2012.0110
   PubMed Web of Science ®Google Scholar
• Rynn MA, Siqueland L, Rickels K. Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. Am J Psychiatry. 2001;158(12):2008–2014.
   PubMed Web of Science ®Google Scholar
• Simeon JG, Ferguson HB, Knott V, et al. Clinical, cognitive, and neurophysiological effects of alprazolam in children and adolescents with overanxious and avoidant disorders. J Am Acad Child Adolesc Psychiatry. 1992;31(1):29–33. DOI:10.1097/00004583-199201000-00006
   PubMed Web of Science ®Google Scholar
• Geller D, Donnelly C, Lopez F, et al. Atomoxetine treatment for pediatric patients with attention-deficit/hyperactivity disorder with comorbid anxiety disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(9):1119–1127. DOI:10.1097/chi.0b013e3180ca8385
   PubMedGoogle Scholar
• Rynn MA, Riddle MA, Yeung PP, et al. Efficacy and safety of extended-release venlafaxine in the treatment of generalized anxiety disorder in children and adolescents: two placebo-controlled trials. Am J Psychiatry. 2007;164(2):290–300. DOI:10.1176/ajp.2007.164.2.290
   PubMedGoogle Scholar
• Strawn JR, Prakash A, Zhang Q, et al. A randomized, placebo-controlled study of duloxetine for the treatment of children and adolescents with generalized anxiety disorder. J Am Acad Child Adolesc Psychiatry. 2015;54(4):283–293. DOI:10.1016/j.jaac.2015.01.008
   PubMed Web of Science ®Google Scholar
• Strawn JR, Compton SN, Robertson B, et al. Extended release guanfacine in pediatric anxiety disorders: a pilot, randomized, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2017;27(1):29–37. DOI:10.1089/cap.2016.0132
   PubMed Web of Science ®Google Scholar
• Hedges DW, Brown BL, Shwalb DA. A direct comparison of effect sizes from the clinical global impression‐improvement scale to effect sizes from other rating scales in controlled trials of adult social anxiety disorder. Hum Psychopharmacol Clin Exp. 2009;24(1):35–40.
   PubMedGoogle Scholar
• Birmaher B, Brent DA, Chiappetta L, et al. Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study. J Am Acad Child Adolesc Psychiatry. 1999;38(10):1230–1236. DOI:10.1097/00004583-199910000-00011
   PubMed Web of Science ®Google Scholar
• Group RAS. The pediatric anxiety rating scale (PARS): development and psychometric properties. J Am Acad Child Adolesc Psychiatry. 2002;41(9):1061–1069.
   PubMed Web of Science ®Google Scholar
• Shaffer D, Gould MS, Brasic J, et al. A Children’s Global Assessment Scale (CGAS). Arch Gen Psychiatry. 1983;40(11):1228–1231. DOI:10.1001/archpsyc.1983.01790100074010
   PubMed Web of Science ®Google Scholar
• Bird HR, Canino G, Rubio-Stipec M, et al. Further measures of the psychometric properties of the children’s global assessment scale. Arch Gen Psychiatry. 1987;44(9):821–824. DOI:10.1001/archpsyc.1987.01800210069011
   PubMedGoogle Scholar
• Shaffer D, Fisher P, Dulcan MK, et al. The NIMH diagnostic interview schedule for children version 2.3 (DISC-2.3): description, acceptability, prevalence rates, and performance in the MECA study. J Am Acad Child Adolesc Psychiatry. 1996;35(7):865–877. DOI:10.1097/00004583-199607000-00012
   PubMed Web of Science ®Google Scholar
• Liebowitz MR. Social phobia. NY: Guilford Publications; 1987.
   Google Scholar
• Watson D, Friend R. Measurement of social-evaluative anxiety. J Consult Clin Psychol. 1969;33(4):448.
   PubMed Web of Science ®Google Scholar
• Mogg K, Bradley BP. Orienting of attention to threatening facial expressions presented under conditions of restricted awareness. Cognit Emotion. 1999;13(6):713–740.
   Web of Science ®Google Scholar
• Swanson JM, Kraemer HC, Hinshaw SP, et al. Clinical relevance of the primary findings of the MTA: success rates based on severity of ADHD and ODD symptoms at the end of treatment. J Am Acad Child Adolesc Psychiatry. 2001;40(2):168–179. DOI:10.1097/00004583-200102000-00011
   PubMed Web of Science ®Google Scholar
• Compton SN, Peris TS, Almirall D, et al. Predictors and moderators of treatment response in childhood anxiety disorders: results from the CAMS trial. J Consult Clin Psychol. 2014;82(2):212. DOI:10.1037/a0035458
   PubMed Web of Science ®Google Scholar
• Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50–55.
   PubMed Web of Science ®Google Scholar
• March. Multidimensional Anxiety Scale for Children (MASC). Toronto Canada: Multi-Health Systems; 1998. Inc.
   Google Scholar
• DuPaul GJ, Power TJ, McGoey KE, et al. Reliability and validity of parent and teacher ratings of attention-deficit/hyperactivity disorder symptoms. J Psychoeducational Assess. 1998;16(1):55–68. DOI:10.1177/073428299801600104
   Web of Science ®Google Scholar
• Chaput F, Fisher P, Klein R, et al. Columbia K-SADS (Schedule for affective disorders and schizophrenia for school-aged children). (NY): Child Psychiatry Intervention Research Center, New York State Psychiatric Institute; 1999.
   Google Scholar
• Strawn JR, Mills JA, Sauley BA, et al. The impact of antidepressant dose and class on treatment response in pediatric anxiety disorders: a meta-analysis. J Am Acad Child Adolesc Psychiatry. 2018;57(4):235–244.e2. DOI:10.1016/j.jaac.2018.01.015
   PubMed Web of Science ®Google Scholar
• Brent DA, Emslie GJ, Clarke GN, et al. Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study. Am J Psychiatry. 2009;166(4):418–426. DOI:10.1176/appi.ajp.2008.08070976
   PubMed Web of Science ®Google Scholar
• Cipriani A, Zhou X, Del Giovane C, et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet. 2016;388(10047):881–890. DOI:10.1016/S0140-6736(16)30385-3
   PubMed Web of Science ®Google Scholar
• Ginsburg GS, Becker-Haimes EM, Keeton C, et al. Results from the Child/Adolescent Anxiety Multimodal Extended Long-Term Study (CAMELS): primary anxiety outcomes. J Am Acad Child Adolesc Psychiatry. 2018;57(7):471–480. DOI:10.1016/j.jaac.2018.03.017
   PubMedGoogle Scholar
• Goldstein-Piekarski A, Williams L, Humphreys K. A trans-diagnostic review of anxiety disorder comorbidity and the impact of multiple exclusion criteria on studying clinical outcomes in anxiety disorders. Transl Psychiatry. 2016;6(6):e847.
   PubMedGoogle Scholar
• Brady EU, Kendall PC. Comorbidity of anxiety and depression in children and adolescents. Psychol Bull. 1992;111(2):244.
   PubMed Web of Science ®Google Scholar
• Khin NA, Chen Y-F, Yang Y, et al. Exploratory analyses of efficacy data from major depressive disorder trials submitted to the US food and drug administration in support of new drug applications. J Clin Psychiatry. 2011;72(4):464–472. DOI:10.4088/JCP.10m06191
   PubMed Web of Science ®Google Scholar
• Rutherford BR, Roose SP. A model of placebo response in antidepressant clinical trials. Am J Psychiatry. 2013;170(7):723–733.
   PubMed Web of Science ®Google Scholar
• Mancini M, Wade AG, Perugi G, et al. Impact of patient selection and study characteristics on signal detection in placebo-controlled trials with antidepressants. J Psychiatr Res. 2014;51:21–29.
   PubMedGoogle Scholar
• Dobson ET, Strawn JR. Placebo response in pediatric anxiety disorders: implications for clinical trial design and interpretation. J Child Adolesc Psychopharmacol. 2016;26(8):686–693.
   PubMedGoogle Scholar
• Bridge JA, Iyengar S, Salary CB, et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007;297(15):1683–1696. DOI:10.1001/jama.297.15.1683
   PubMed Web of Science ®Google Scholar
• Dwyer JB, Bloch MH. Antidepressants for pediatric patients. Curr Psychiatr. 2019;18(9):26–42f.
   PubMedGoogle Scholar
• Walkup J, Labellarte M. Complications of SSRI treatment. J Child Adolesc Psychopharmacol. 2001;11(1):1–4.
   PubMed Web of Science ®Google Scholar