Advertisement

Efficacy and safety of mixed amphetamine salts extended release (adderall XR) in the management of oppositional defiant disorder with or without comorbid attention-deficit/hyperactivity disorder in school-aged children and adolescents: A 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Background:

      Oppositional defiant disorder (ODD)is associated with a high degree of impairment in social skills, family interaction, and academic functioning. Comorbid ODD is reportedly present in 40% to 70% of children and adolescents with attention-deficit/hyperactivity disorder (ADHD).

      Objective:

      The goal of this study was to assess theefficacy and safety of mixed amphetamine salts extended release (MAS XR) for the treatment of ODD in children and adolescents aged 6 to 17 years.

      Methods:

      This was a 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study. Patients were randomized to receive active treatment with MAS XR 10, 20, 30, or 40 mg/d or placebo. The primary efficacy end point was the ODD subscale of the Swanson, Nolan, and Pelham-IV (SNAP-IV) parent rating. Primary safety measures included adverse events recorded at each visit and for 30 days after study drug discontinuation, and changes in vital signs, 12-lead electrocardiographic (ECG) findings, laboratory tests and physical examinations, and body weight. A post hoc efficacy reanalysis was completed based on the results for the per-protocol population. For this analysis, patients were divided into high and low baseline severity categories according to the dichotomized baseline ODD parent or teacher score or dichotomized baseline ADHD parent or teacher score (high defined as scores at the median or greater and low defined as scores less than the median).

      Results:

      A total of 308 children and adolescents (age range, 6–17 years; 213 males, 95 females) were randomized to receive active treatment with MAS XR 10 mg/d (n = 60) 20 mg/d (n = 58), 30 mg/d (n = 69), or 40 mg/d (n = 61) or placebo (n = 60). Of the 308 study patients, 244 (79.2%) had comorbid ADHD. A significant change from baseline in the ODD symptoms measured with the SNAP-IV parent rating subscale was found for the MAS XR 30-mg/d (-0.52; P < 0.001) and 40-mg/d (−0.56; P = 0.002) groups in the per-protocol analysis and for the MAS XR 30-mg/d group in the intent-to-treat analysis (−0.42; P < 0.005). Throughout the study, MAS XR was well tolerated in these children and adolescents with ODD, and most adverse events were mild to moderate in intensity. The most frequently reported adverse events occurring in MAS XR-treated patients were anorexia/decreased appetite (25.3%), insomnia (19.5%), headache (18.5%), and abdominal pain (10.7%). Statistically, but not clinically, significant decreases in body weight were seen with MAS XR (range, -1.1 to −3.5 lb; P < 0.001 vs placebo). Changes in laboratory values, ECG measurements, and physical and other vital signs were also not clinically significant. The post hoc reanalysis was based on the per-protocol population (n = 229). An assessment of the high baseline symptom severity subgroups showed a good response to MAS XR treatment for the SNAP-IV parent and teacher rating scales (both, P < 0.05).

      Conclusion:

      This study found that higher doses ofMAS XR (30 and 40 mg) were effective and well tolerated in the management of ODD in these schoolaged children and adolescents in the presence or absence of ADHD.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Loeber R.
        • Burke J.D.
        • Lahey B.B.
        • et al.
        Oppositional defiant and conduct disorder: A review of the past 10 years, part I.
        J Am Acad Child Adolesc Psychiatry. 2000; 39: 1468-1484
      1. (Available at:)
        • American Academy of Child & Adolescent Psychiatry
        Children with oppositional defiant disorder. Facts for families. No. 72.
        (Accessed)January 4, 2005
      2. (Text Revision)
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders.
        Fourth Edition. American Psychiatric Association, Washington, DC2000
        • Maughan B.
        • Rowe R.
        • Messer J.
        • et al.
        Conduct disorder and oppositional defiant disorder in a national sample: Developmental epidemiology.
        J Child Psychol Psychiatry. 2004; 45: 609-621
        • Anastopoulos A.D.
        • Guevremont D.C.
        • Shelton T.L.
        • DuPaul G.J.
        Parenting stress among families of children with attention deficit hyperactivity disorder.
        J Abnorm Child Psychol. 1992; 20: 503-520
        • Greene R.W.
        • Biederman J.
        • Zerwas S.
        • et al.
        Psychiatric comorbidity, family dysfunction, and social impairment in referred youth with oppositional defiant disorder.
        Am J Psychiatry. 2002; 159: 1214-1224
        • Wells K.C.
        • Epstein J.N.
        • Hinshaw S.P.
        • et al.
        Parenting and family stress treatment outcomes in attention deficit hyperactivity disorder (ADHD): An empirical analysis in the MTA study.
        J Abnorm Child Psychol. 2000; 28: 543-553
        • Anderson J.C.
        • Williams S.
        • McGee R.
        • Silva P.A.
        DSM-III disorders in preadolescent children. Prevalence in a large sample from the general population.
        Arch Gen Psychiatry. 1987; 44: 69-76
        • Bird H.R.
        • Canino G.
        • Rubio-Stipec M.
        • et al.
        Estimates of the prevalence of childhood maladjustment in a community survey in Puerto Rico. The use of combined measures.
        Arch Gen Psychiatry. 1988; 45 ([published correction appears in Arch Gen Psychiatry. 1994;51:429]): 1120-1126
        • Bird H.R.
        • Gould M.S.
        • Staghezza B.M.
        Patterns of diagnostic comorbidity in a community sample of children aged 9 through 16 years.
        J Am Acad Child Adolesc Psychiatry. 1993; 32: 361-368
        • Szatmari P.
        • Boyle M.
        • Offord D.R.
        ADDH and conduct disorder: Degree of diagnostic overlap and dif ferences among correlates.
        J Am Acad Child Adolesc Psychiatry. 1989; 28: 865-872
        • Barkley R.A.
        • Fischer M.
        • Edelbrock C.S.
        • Smallish L.
        The adolescent outcome of hyperactive children diag nosed by research criteria: I. An 8-year prospective follow-up study.
        J Am Acad Child Adolesc Psychiatry. 1990; 29: 546-557
        • Barkley R.A.
        • McMurray M.B.
        • Edelbrock C.S.
        • Robbins K.
        The response of aggressive and nonaggres sive ADHD children to two doses of methylphenidate.
        J Am Acad Child Adolesc Psychiatry. 1989; 28 ([published correction appears in J Am Acad Child Adolesc Psychiatry. 1990;29:670]): 873-881
        • Burns G.L.
        • Walsh J.A.
        The influence of ADHD-hyperactivity/impulsivity symptoms on the development of oppositional defiant disorder symptoms in a 2-year longitudinal study.
        J Abnorm Child Psychol. 2002; 30: 245-256
        • Kadesjo C.
        • Hagglof B.
        • Kadesjo B.
        • Gillberg C.
        Attentiondeficit-hyperactivity disorder with and with out oppositional defiant disorder in 3- to 7-year-old children.
        Dev Med Child Neurol. 2003; 45: 693-699
        • Jensen P.S.
        • Hinshaw S.P.
        • Kraemer H.C.
        • et al.
        ADHD comorbidity findings from the MTA study: Compar ing comorbid subgroups.
        J Am Acad Child Adolesc Psychiatry. 2001; 40: 147-158
        • Abikoff H.
        • Hechtman L.
        • Klein R.G.
        • et al.
        Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment.
        J Am Acad Child Adolesc Psychiatry. 2004; 43: 802-811
        • Newcorn J.H.
        • Spencer T.J.
        • Biederman J.
        • et al.
        Atomoxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder.
        J Am Acad Child Adolesc Psychiatry. 2005; 44: 240-248
        • Swanson J.M.
        • Kraemer H.C.
        • Hinshaw S.P.
        • 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: 168-179
      3. (Revised.)
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders. Third Edition. American Psychiatric Association, Washington, DC1987
        • Landgraf J.M.
        • Abetz L.
        • Ware J.E.
        The CHQ: A User's Manual.
        2nd ed. HealthAct, Boston, Mass1999
        • Clinical Global Impressions (CGI)
        Guy W. ECDEU Assessment Manual for Psychopharmacology. US Dept of Health and Human Services, Public Health Service, Alcohol Drug Abuse and Mental Health Administration, National Institute of Mental Health Psych opharmacology Research Branch, Rockville, Md1976: 218-222
      4. Coding Symbols for Thesaurus of Adverse Reaction Terms (COSTART).
        5th ed. US Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, Md1995
        • Sallee F.R.
        • Ambrosini P.J.
        • Lopez F.A.
        • et al.
        Health-related quality of life and treatment satisfaction and preference in a community assessment study of extended-release mixed amphetamine salts for children with attention-deficit/hyperactivity disorder.
        J Outcomes Res. 2004; 8: 27-49
        • Harada Y.
        • Yamazaki T.
        • Saitoh K.
        Psychosocial problems in attentiondeficit hyperactivity disorder with oppositional defiant disorder.
        Psychiatry Clin Neurosci. 2002; 56: 365-369
      5. Adderall XR. Shire US Inc, Wayne, Pa2004
        • McCracken J.T.
        • Biederman J.
        • Greenhill L.L.
        • et al.
        Analog classroom assessment of a once-daily mixed amphetamine formulation, SLI381 (Adderall XR), in children with AD HD.
        J Am Acad Child Adolesc Psychiatry. 2003; 42: 673-683
        • Biederman J.
        • Lopez F.A.
        • Boellner S.W.
        • Chandler M.C.
        A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attentiondeficit/hyperactivity disorder.
        Pediatrics. 2002; 110: 258-266
      6. (Washington, DC)
        • Grcevich S.
        • Read S.C.
        • Sea D.
        • et al.
        Safety and efficacy of MAS XR in adolescents with ADHD.
        in: Poster presented at the 51st Annual Meeting of the American Academy of Child and Adolescent Psychiatry. October 20, 2004
      7. (Miami, Fla)
        • Findling R.L.
        • Biederman J.
        • Wilens T.E.
        • et al.
        Cardiovascular effects of extended-release mixed amphetamine salts.
        in: Poster presented at: 50th Annual Meeting of the American Academy of Child and Adolescent Psychiatry. October 18, 2003