Effective Medications for Treating Internalizing Disorders

  • Brian Smith
  • Alyse Ley
  • Katherine Krive
  • Jed MagenEmail author
Part of the Pediatric School Psychology book series (PSP)


Internalizing disorders, which encompass anxiety and depressive disorders, are a challenge to both diagnose and treat in the school-age population. The purpose of this chapter is to highlight the efficacy and effectiveness of psychotropic medications used in the treatment of school-aged children exhibiting internalizing behavior disorders including anxiety and depression. Both the intended and side effects of medication treatments (SSRIs, SNRIs) commonly used to treat these internalizing disorders are reviewed. A set of references and web-based materials are provided to readers for additional information.


Anxiety Depression Internalizing SSRIs SNRIs Antidepressants Psychopharmacology 


  1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.CrossRefGoogle Scholar
  2. Ban, T. A. (2006). The role of serendipity in drug discovery. Dialogues in Clinical Neuroscience, 8(3), 335–344.PubMedPubMedCentralGoogle Scholar
  3. Bavdekar, S. B. (2013). Pediatric clinical trials. Perspectives in Clinical Research, 4(1), 89–99. Scholar
  4. Beidel, D. C., Turner, S. M., & Morris, T. L. (2000). Behavioral treatment of childhood social phobia. Journal of Consulting and Clinical Psychology, 68(6), 1072–1080. Scholar
  5. Birmaher, B., Brent, D., & AACAP Work Group on Quality Issues. (2007). Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. Journal of the American Academy of Child and Adolescent Psychiatry, 46(11), 1503–1526. Scholar
  6. Birmaher, B., Ryan, N. D., Williamson, D. E., Brent, D. A., Kaufman, J., Dahl, R. E., … Nelson, B. (1996). Childhood and adolescent depression: A review of the past 10 years. Part I. Journal of the American Academy of Child & Adolescent Psychiatry35(11), 1427–1439. Scholar
  7. Brent, D. A., Baugher, M., Bridge, J., Chen, T., & Chiappetta, L. (1999). Age-and sex-related risk factors for adolescent suicide. Journal of the American Academy of Child and Adolescent Psychiatry, 38(12), 1497–1505. Scholar
  8. Brent, D., Emslie, G., Clarke, G., Wagner, K. D., Asarnow, J. R., Keller, M., … Birmaher, B. (2008). Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. JAMA299(8), 901–913.CrossRefGoogle Scholar
  9. Bridge, J. A., Iyengar, S., Salary, C. B., Barbe, R. P., Birmaher, B., Pincus, H. A., … Brent, D. A. (2007). Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA297(15), 1683–1696. Scholar
  10. Cohen, J., & The AACAP Work Group on Quality Issues. (2010). Practice parameter for the assessment and treatment of children and adolescents with posttraumatic stress disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 49, 414–430. Scholar
  11. Cohen, J. A., Mannarino, A. P., Perel, J. M., & Staron, V. (2007). A pilot randomized controlled trial of combined trauma-focused CBT and sertraline for childhood PTSD symptoms. Journal of the American Academy of Child and Adolescent Psychiatry, 46(7), 811–819. Scholar
  12. Connolly, S. D., & Bernstein, G. A. (2007). Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders. Journal of the American Academy of Child and Adolescent Psychiatry, 46(2), 267–283. Scholar
  13. Dulcan, M. (Ed.). (2015). Dulcan’s textbook of child and adolescent psychiatry (2nd ed.). Arlington, VA: American Psychiatric Publishing.Google Scholar
  14. Fergusson, D. M., & Woodward, L. J. (2002). Mental health, educational, and social role outcomes of adolescents with depression. Archives of General Psychiatry, 59(3), 225–231. Scholar
  15. Geller, D. A., Biederman, J., Stewart, S. E., Mullin, B., Martin, A., Spencer, T., & Faraone, S. V. (2003). Which SSRI? A meta-analysis of pharmacotherapy trials in pediatric obsessive-compulsive disorder. American Journal of Psychiatry, 160(11), 1919–1928. Scholar
  16. Geller, D. A., & March, J. (2012). Practice parameter for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. Focus, 10(3), 360–373. Scholar
  17. Hammad, T. A., Laughren, T., & Racoosin, J. (2006). Suicidality in pediatric patients treated with antidepressant drugs. Archives of General Psychiatry, 63(3), 332–339. doi: Scholar
  18. Hawton, K., & van Heeringen, K. (2009). Suicide. Lancet, 373(9672), 1372–1381. Scholar
  19. Hyman, S. E. (2013, March). Psychiatric drug development: diagnosing a crisis. In Cerebrum: The Dana forum on brain science (Vol. 2013). Dana Foundation.Google Scholar
  20. Kendall, P. C. (1994). Treating anxiety disorders in children: Results of a randomized clinical trial. Journal of Consulting and Clinical Psychology, 62(1), 100–110. Scholar
  21. Kessler, R. C., Angermeyer, M., Anthony, J. C., De Graaf, R. O. N., Demyttenaere, K., Gasquet, I., … Kawakami, N. (2007). Lifetime prevalence and age-of-onset distributions of mental disorders in the world health organization’s world mental health survey initiative. World Psychiatry6(3), 168–176.Google Scholar
  22. Ialongo, et al. (1995). The significance of self-reported anxious symptoms in first grade children: Prediction to anxious symptoms and adaptive functioning in fifth grade. Journal of Child Psychology Psychiatry, 36, 427–437.CrossRefGoogle Scholar
  23. Last, C. G., Perrin, S., Hersen, M., & Kazdin, A. E. (1996). A prospective study of childhood anxiety disorders. Journal of the American Academy of Child and Adolescent Psychiatry, 35(11), 1502–1510. Scholar
  24. March, J., Silva, S., Petrycki, S., Curry, J., Wells, K., Fairbank, J., … Severe, J. (2004). Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents with Depression Study (TADS) randomized controlled trial. JAMA, 292(7), 807–820.
  25. Medicaid Integrity Group (2013, August). Antidepressant medications: Use in pediatric patients. Retrieved from:
  26. Merikangas, K. R., He, J. P., Burstein, M., Swanson, S. A., Avenevoli, S., Cui, L., … Swendsen, J. (2010). Lifetime prevalence of mental disorders in US adolescents: Results from the national comorbidity survey replication–adolescent supplement (NCS-A). Journal of the American Academy of Child & Adolescent Psychiatry, 49(10), 980–989. Scholar
  27. Merikangas, K. R., He, J. P., Burstein, M., Swendsen, J., Avenevoli, S., Case, B., … Olfson, M. (2011). Service utilization for lifetime mental disorders in US adolescents: Results of the national comorbidity survey–adolescent supplement (NCS-A). Journal of the American Academy of Child & Adolescent Psychiatry, 50(1), 32–45. Scholar
  28. Mulinari, S. (2015). Divergence and convergence of commercial and scientific priorities in drug development: The case of Zelmid, the first SSRI antidepressant. Social Science and Medicine, 138, 217–224. Scholar
  29. O’Sullivan, K., Reulbach, U., Boland, F., Motterlini, N., Kelly, D., Bennett, K., & Fahey, T. (2015). Benzodiazepine prescribing in children under 15 years of age receiving free medical care on the general medical services scheme in Ireland. BMJ Open, 5(6), e007070. Scholar
  30. Pediatric OCD Treatment Team. (2004). Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: The pediatric OCD treatment study (POTS) randomized controlled trial. JAMA, 292(16), 1969–1976. Scholar
  31. Perez-Caballero, L., Torres-Sanchez, S., Bravo, L., Mico, J. A., & Berrocoso, E. (2014). Fluoxetine: a case history of its discovery and preclinical development. Expert Opinion on Drug Discovery, 9(5), 567–578. Scholar
  32. Poirier, M., Déry, M., Toupin, J., Verlaan, P., Lemelin, J. P., & Jagiellowicz, J. (2015). Correlates of conduct problems and depression comorbidity in elementary school boys and girls receiving special educational services. Psychology in the Schools, 52(4), 403–418. Scholar
  33. Ramachandraih, C. T., Subramanyam, N., Bar, K. J., Baker, G., & Yeragani, V. K. (2011). Antidepressants: From MAOIs to SSRIs and more. Indian Journal of Psychiatry, 53(2), 180–182. Scholar
  34. Rynn, M., Puliafico, A., Heleniak, C., Rikhi, P., Ghalib, K., & Vidair, H. (2011). Advances in pharmacotherapy for pediatric anxiety disorders. Depression and Anxiety, 28(1), 76–87. Scholar
  35. Rynn, M. A., Siqueland, L., & Rickels, K. (2001). Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. American Journal of Psychiatry, 158(12), 2008–2014. Scholar
  36. Siegel, R. S., & Dickstein, D. P. (2012). Anxiety in adolescents: Update on its diagnosis and treatment for primary care providers. Adolescent Health, Medicine and Therapeutics, 3, 1–16. Scholar
  37. Small, D. M., Simons, A. D., Yovanoff, P., Silva, S. G., Lewis, C. C., Murakami, J. L., & March, J. (2008). Depressed adolescents and comorbid psychiatric disorders: are there differences in the presentation of depression? Journal of Abnormal Child Psychology, 36(7), 1015–1028. Scholar
  38. Southammakosane, C., & Schmitz, K. (2015). Pediatric psychopharmacology for treatment of ADHD, depression, and anxiety. Pediatrics, 136(2), 351–359. Scholar
  39. Strawn, J. R., Welge, J. A., Wehry, A. M., Keeshin, B., & Rynn, M. A. (2015). Efficacy and tolerability of antidepressants in pediatric anxiety disorders: A systematic review and meta-analysis. Depression and Anxiety, 32(3), 149–157. Scholar
  40. Taylor, A. M. (2015, March). Pediatric focused safety review: Cymbalta (duloxetine). Retrieved from
  41. Valluri, S., Zito, J. M., Safer, D. J., Zuckerman, I. H., Mullins, C. D., & Korelitz, J. J. (2010). Impact of the 2004 food and drug administration pediatric suicidality warning on antidepressant and psychotherapy treatment for new-onset depression. Medical Care, 48(11), 947–954. Scholar
  42. Van Ameringen, M., Mancini, C., & Farvolden, P. (2003). The impact of anxiety disorders on educational achievement. Journal of Anxiety Disorders, 17(5), 561–571. Scholar
  43. von der Embse, N., Barterian, J., & Segool, N. (2013). Test anxiety interventions for children and adolescents: A systematic review of treatment studies from 2000–2010. Psychology in the Schools, 50(1), 57–71. Scholar
  44. Walkup, J. T., Albano, A. M., Piacentini, J., Birmaher, B., Compton, S. N., Sherrill, J. T., … Iyengar, S. (2008). Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. New England Journal of Medicine, 359(26), 2753–2766. Scholar
  45. Whittington, C. J., Kendall, T., Fonagy, P., Cottrell, D., Cotgrove, A., & Boddington, E. (2004). Selective serotonin reuptake inhibitors in childhood depression: Systematic review of published versus unpublished data. Lancet, 363(9418), 1341–1345.CrossRefGoogle Scholar
  46. Zhou, X., Qin, B., Whittington, C., Cohen, D., Liu, Y., Del Giovane, C., … Xie, P. (2015). Comparative efficacy and tolerability of first-generation and newer-generation antidepressant medications for depressive disorders in children and adolescents: Study protocol for a systematic review and network meta-analysis. BMJ Open, 5(9), e007768.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Brian Smith
    • 1
  • Alyse Ley
    • 1
  • Katherine Krive
    • 1
  • Jed Magen
    • 1
    Email author
  1. 1.Michigan State UniversityEast LansingUSA

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