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Safety, Tolerability, and Efficacy of Desvenlafaxine in Children and Adolescents with Major Depressive Disorder: Results from Two Open-Label Extension Trials

Published online by Cambridge University Press:  13 November 2018

Sarah Atkinson Open the ORCID record for Sarah Atkinson [Opens in a new window] ,
Louise Thurman ,
Sara Ramaker ,
Gina Buckley ,
Sarah Ruta Jones ,
Richard England  and
Dalia Wajsbrot
Sarah Atkinson*
Affiliation:
Finger Lakes Clinical Research, Rochester, New York
Louise Thurman
Affiliation:
IPS Research, Oklahoma City, Oklahoma
Sara Ramaker
Affiliation:
Pfizer Inc., Collegeville, Pennsylvania
Gina Buckley
Affiliation:
Pfizer Inc., Collegeville, Pennsylvania
Sarah Ruta Jones
Affiliation:
Pfizer Inc., Collegeville, Pennsylvania
Richard England
Affiliation:
Pfizer Inc., Groton, Connecticut
Dalia Wajsbrot
Affiliation:
Pfizer Inc., New York, New York
*
*Address for correspondence: Sarah Atkinson, Finger Lakes Clinical Research, 885 S. Winton Road, Rochester, NY 14618, USA. (Email: [email protected])
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Abstract

Objective

Two similarly designed extension studies evaluated the long-term safety and tolerability of desvenlafaxine for the treatment of children and adolescents with major depressive disorder (MDD). Efficacy was evaluated as a secondary objective.

Methods

Both 6-month, open-label, flexible-dose extension studies enrolled children and adolescents who had completed one of two double-blind, placebo-controlled, lead-in studies. One lead-in study included a 1-week transition period prior to the extension study. Patients received 26-week treatment with flexible-dose desvenlafaxine (20–50 mg/d). Safety assessments included comprehensive psychiatric evaluations, vital sign assessments, laboratory evaluations, 12-lead electrocardiogram, physical examination with Tanner assessment, and Columbia-Suicide Severity Rating Scale. Adverse events (AEs) were collected throughout the studies. Efficacy was assessed using the Children’s Depression Rating Scale–Revised (CDRS-R).

Results

A total of 552 patients enrolled (completion rates: 66.4 and 69.1%). AEs were reported by 79.4 and 79.1% of patients in the two studies; 8.9 and 5.2% discontinued due to AEs. Treatment-emergent suicidal ideation or behavior was reported for 16.6 and 14.1% of patients in the two studies. Mean (SD) CDRS-R total score decreased from 33.83 (11.93) and 30.92 (10.20) at the extension study baseline to 24.31 (7.48) and 24.92 (8.45), respectively, at week 26.

Conclusion

Desvenlafaxine 20 to 50 mg/d was generally safe and well tolerated with no new safety signals identified in children and adolescents with MDD who received up to 6 months of treatment in these studies. Patients maintained the reduction in severity of depressive symptoms observed in all treatment groups at the end of the lead-in study.

Keywords

Adolescentsantidepressantchildrenclinical trialsafety
Type
Original Research
Information
CNS Spectrums , Volume 24 , Issue 5 , October 2019 , pp. 496 - 506
Copyright
© Cambridge University Press 2018 

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Footnotes

This study was sponsored by Pfizer. Medical writing support was provided by Kathleen M. Dorries, PhD, of Peloton Advantage and was funded by Pfizer Inc.ClinicalTrials.gov Identifiers: NCT01371708, NCT01371721

References

Fergusson, DM, Boden, JM, Horwood, LJ. Recurrence of major depression in adolescence and early adulthood, and later mental health, educational and economic outcomes. Br J Psychiatry. 2007; 191: 335–342.CrossRefGoogle ScholarPubMed
Kovacs, M, Obrosky, S, George, C. The course of major depressive disorder from childhood to young adulthood: Recovery and recurrence in a longitudinal observational study. J Affect Disord. 2016; 203: 374–381.CrossRefGoogle Scholar
Birmaher, B, Arbelaez, C, Brent, D. Course and outcome of child and adolescent major depressive disorder. Child Adolesc Psychiatr Clin N Am. 2002; 11(3): 619–637.CrossRefGoogle ScholarPubMed
Hirschfeld, RM, Vornik, LA. Recognition and diagnosis of bipolar disorder. J Clin Psychiatry. 2004; 65(suppl 15): 5–9.Google ScholarPubMed
Okasha, T, Fikry, M, Kowailed, A, El-Guwiely, T, Sadek, H. Screening for bipolar disorder among patients undergoing a major depressive episode: report from the BRIDGE study in Egypt. J Affect Disord. 2013; 147(1–3): 217–224.CrossRefGoogle Scholar
Bouchra, O, Maria, S, Abderazak, O. Screening of the unrecognised bipolar disorders among outpatients with recurrent depressive disorder: a cross-sectional study in psychiatric hospital in Morocco. Pan Afr Med J. 2017; 27: 247.Google ScholarPubMed
Martin, A, Young, C, Leckman, JF, Mukonoweshuro, C, Rosenheck, R, Leslie, D. Age effects on antidepressant-induced manic conversion. Arch Pediatr Adolesc Med. 2004; 158(8): 773–780.CrossRefGoogle ScholarPubMed
Siu, AL. Screening for Depression in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016; 164(5): 360–366.CrossRefGoogle ScholarPubMed
Birmaher, B, Ryan, ND, Williamson, DE, et al. Childhood and adolescent depression: a review of the past 10 years. Part I. J Am Acad Child Adolesc Psychiatry. 1996; 35(11): 1427–1439.CrossRefGoogle ScholarPubMed
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(11): 1503–1526.CrossRefGoogle ScholarPubMed
Wilson, S, Hicks, BM, Foster, KT, McGue, M, Iacono, WG. Age of onset and course of major depressive disorder: associations with psychosocial functioning outcomes in adulthood. Psychol Med. 2015; 45(3): 505–514.CrossRefGoogle ScholarPubMed
Oluboka, OJ, Katzman, MA, Habert, J, et al. Functional recovery in major depressive disorder: providing early optimal treatment for the individual patient. Int J Neuropsychopharmacol. 2018; 21(2): 128–144.CrossRefGoogle ScholarPubMed
Cheung, AH, Zuckerbrot, RA, Jensen, PS, Ghalib, K, Laraque, D, Stein, RE. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): II. Treatment and ongoing management. Pediatrics. 2007; 120(5): e1313–e1326.CrossRefGoogle ScholarPubMed
Emslie, GJ, Rush, AJ, Weinberg, WA, et al. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry. 1997; 54(11): 1031–1037.CrossRefGoogle ScholarPubMed
Emslie, GJ, Heiligenstein, JH, Wagner, KD, et al. Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial. J Am Acad Child Adolesc Psychiatry. 2002; 41(10): 1205–1215.CrossRefGoogle ScholarPubMed
Wagner, KD, Ambrosini, P, Rynn, M, et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA. 2003; 290(8): 1033–1041.CrossRefGoogle ScholarPubMed
Emslie, GJ, Ventura, D, Korotzer, A, Tourkodimitris, S. Escitalopram in the treatment of adolescent depression: a randomized placebo-controlled multisite trial. J Am Acad Child Adolesc Psychiatry. 2009; 48(7): 721–729.CrossRefGoogle ScholarPubMed
Wagner, KD, Robb, AS, Findling, RL, Jin, J, Gutierrez, MM, Heydorn, WE. A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents. Am J Psychiatry. 2004; 161(6): 1079–1083.CrossRefGoogle ScholarPubMed
Emslie, GJ, Heiligenstein, JH, Hoog, SL, et al. Fluoxetine treatment for prevention of relapse of depression in children and adolescents: a double-blind, placebo-controlled study. J Am Acad Child Adolesc Psychiatry. 2004; 43(11): 1397–1405.CrossRefGoogle ScholarPubMed
Emslie, GJ, Kennard, BD, Mayes, TL, et al. Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents. Am J Psychiatry. 2008; 165(4): 459–467.CrossRefGoogle ScholarPubMed
Cox, GR, Fisher, CA, De Silva, S, et al. Interventions for preventing relapse and recurrence of a depressive disorder in children and adolescents. Cochrane Database Syst Rev. 2012; 11: CD007504.Google ScholarPubMed
Kennard, BD, Emslie, GJ, Mayes, TL, et al. Sequential treatment with fluoxetine and relapse--prevention CBT to improve outcomes in pediatric depression. Am J Psychiatry. 2014; 171(10): 1083–1090.CrossRefGoogle ScholarPubMed
Hughes, CW, Emslie, GJ, Crismon, ML, et al. Texas Children’s Medication Algorithm Project: update from Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. J Am Acad Child Adolesc Psychiatry. 2007; 4(6): 667–686.CrossRefGoogle Scholar
Prozac package insert. Indianapolis, IN: Eli Lilly and Company; 2017.Google Scholar
Lexapro package insert. St. Louis, MO: Forest Pharmaceuticals Inc.; 2017.Google Scholar
Pristiq package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.; 2017.Google Scholar
Atkinson, S, Lubaczewski, S, Ramaker, S, et al. Desvenlafaxine versus placebo in the treatment of children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2018; 28(1): 55–65.CrossRefGoogle ScholarPubMed
Weihs, K, Murphy, W, Abbas, R, et al. Desvenlafaxine vs placebo in a fluoxetine-referenced study of children and adolescents with MDD. J Child Adolesc Psychopharmacol. 2018; 28(1):34–36.CrossRefGoogle Scholar
International Council for Harmonisation. ICH Harmonised Tripartite Guideline: Statistical Principles for Clinical Trials E9. http://www.ich.org/products/guidelines/efficacy/efficacy-single/article/statistical-principles-for-clinical-trials.html. Accessed May 15, 2017.Google Scholar
Kaufman, J, Birmaher, B, Brent, D, et al. Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997; 36(7): 980–988.CrossRefGoogle ScholarPubMed
Weihs, KL, Murphy, W, Abbas, R, et al. Desvenlafaxine versus placebo in a fluoxetine-referenced study of children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2018; 28(1): 36–46.CrossRefGoogle Scholar
Posner, K, Brent, D, Lucas, C, et al. Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline. New York: Columbia University Medical Center. http://cssrs.columbia.edu/wp-content/uploads/C-SSRS1-14-09-Baseline.pdf. Accessed September 8, 2018.Google Scholar
Posner, K, Brent, D, Lucas, C, et al. Columbia-Suicide Severity Rating Scale (C-SSRS), Since Last Visit. New York: Columbia University Medical Center. http://cssrs.columbia.edu/wp-content/uploads/C-SSRS1-14-09-SinceLastVisit.pdf. Accessed September 8, 2018.Google Scholar
Carrasco, JL, Kornstein, SG, McIntyre, RS, et al. An integrated analysis of the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder. Int Clin Psychopharmacol. 2016; 31(3): 134–146.CrossRefGoogle ScholarPubMed
Atkinson, SD, Prakash, A, Zhang, Q, et al. A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2014; 24(4): 180–189.CrossRefGoogle ScholarPubMed
Emslie, GJ, Prakash, A, Zhang, Q, Pangallo, BA, Bangs, ME, March, JS. A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2014; 24(4): 170–179.CrossRefGoogle ScholarPubMed
Findling, RL, Robb, A, Bose, A. Escitalopram in the treatment of adolescent depression: a randomized, double-blind, placebo-controlled extension trial. J Child Adolesc Psychopharmacol. 2013; 23(7): 468–480.CrossRefGoogle ScholarPubMed
Rynn, M, Wagner, KD, Donnelly, C, et al. Long-term sertraline treatment of children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2006; 16(1–2): 103–116.CrossRefGoogle ScholarPubMed
Findling, RL, Groark, J, Chiles, D, Ramaker, S, Yang, L, Tourian, KA. Safety and tolerability of desvenlafaxine in children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2014; 24(4): 201–209.CrossRefGoogle ScholarPubMed
Hammad, TA, Laughren, T, Racoosin, J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry. 2006; 63(3): 332–339.CrossRefGoogle ScholarPubMed
Medicines and Healthcare Products Regulatory Agency. Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs): Use and Safety. 2014. https://www.gov.uk/government/publications/ssris-and-snris-use-and-safety/selective-serotonin-reuptake-inhibitors-ssris-and-serotonin-and-noradrenaline-reuptake-inhibitors-snris-use-and-safety. Accessed June 26, 2017.Google Scholar
Young, AS, Meers, MR, Vesco, AT, Seidenfeld, AM, Arnold, LE, Fristad, MA. Predicting therapeutic effects of psychodiagnostic assessment among children and adolescents participating in randomized controlled trials. J Clin Child Adolesc Psychol. 2016: 1–12. doi: 10.1080/15374416.2016.1146992.Google ScholarPubMed
Emslie, GJ, Ryan, ND, Wagner, KD. Major depressive disorder in children and adolescents: clinical trial design and antidepressant efficacy. J Clin Psychiatry. 2005; 66(suppl 7): 14–20.Google ScholarPubMed
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