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The effects of atomoxetine on emotional control in adults with ADHD: An integrated analysis of multicenter studies

Published online by Cambridge University Press:  15 April 2020

P. Asherson ,
S. Stes ,
M. Nilsson Markhed ,
L. Berggren ,
P. Svanborg ,
A. Kutzelnigg  and
W. Deberdt
P. Asherson*
Affiliation:
Social, Genetic and Developmental Psychiatry, Institute of Psychiatry, King's College London, De Crespigny ParkSE5 8AF, United Kingdom
S. Stes
Affiliation:
ADHD Program, University Psychiatric Center, KU Leuven, Leuvensesteenweg 517, Campus Kortenberg, Belgium Code Thomas More, Jozef De Bomstraat 11, 2018Antwerpen, Belgium
M. Nilsson Markhed
Affiliation:
Department of Psychiatry, Uppsala University, 751 85, Uppsala, Sweden
L. Berggren
Affiliation:
Global Statistical Sciences, Eli Lilly & Co., Werner Reimers Str. 2-4, 61350Bad Homburg, Germany
P. Svanborg
Affiliation:
Neuroscience, Eli Lilly & Co., Sweden AB, Gustav III Boulevard 42, PO box 721, SE-169 27Solna, Sweden
A. Kutzelnigg
Affiliation:
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
W. Deberdt
Affiliation:
Medical Department, Eli Lilly & Co., Markiesstraat 1, 1000Brussels, Belgium
*
⁎Corresponding author. Tel.: +44 0207 8480 078. E-mail address:philip.asherson@kcl.ac.uk (P. Asherson).
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Abstract

Purpose:

To investigate the effects of atomoxetine on emotional control in adults with ADHD.

Methods:

We performed an integrated analysis using individual patient data pooled from three Eli Lilly-sponsored studies. An integrated analysis can be viewed as a meta-analysis of individual patient-level data, rather than study-level summary data.

Results:

Two populations were identified: a large sample of patients with pre-treatment baseline data (the “overall population”; n = 2846); and a subset of these patients with placebo-controlled efficacy data from baseline to 10 or 12 weeks after initiating treatment (the “placebo-controlled population”; n = 829). At baseline, in the overall population, ∼50% of ADHD patients had BRIEF-AS (Behavior Rating Inventory of Executive Function-Adult Version Self-Report) Emotional control subscores between 21 and 30, compared with ∼10% of normative subjects in the BRIEF-A manual. At endpoint, in the placebo-controlled population, atomoxetine led to a small (effect size 0.19) but significant (P = 0.013) treatment effect for emotional control. The effect size was 0.32 in patients with BRIEF-AS Emotional control scores > 20 at baseline. Improvements in emotional control correlated with improvements in the core ADHD symptoms and quality-of-life.

Discussion:

As deficient emotional control is associated with impaired social, educational and occupational functioning over and above that explained by core ADHD symptoms alone, improvements in emotional control may be clinically relevant.

Conclusion:

At baseline, adults with ADHD were more likely to have impaired emotional control than normative subjects. In the adult ADHD patients, atomoxetine treatment was associated with improvements in emotional control, as well as in core ADHD symptoms and quality-of-life.

Keywords

AtomoxetineADHDEmotional controlIntegrated analysis
Type
Original article
Information
European Psychiatry , Volume 30 , Issue 4 , June 2015 , pp. 511 - 520
Copyright
Copyright © Elsevier Masson SAS 2015

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References

Adler, LA, Spencer, TJ, Williams, DW, Moore, RJ, Michelson, DLong-term, open-label safety and efficacy of atomoxetine in adults with ADHD: final report of a 4-year study. J Atten Disord 2008;12(3):248–253. [PubMed: 18448861].CrossRefGoogle ScholarPubMed
Adler, LA, Clemow, DB, Williams, DW, Durell, TMAtomoxetine effects on executive function as measured by the BRIEF--A in young adults with ADHD: a randomized, double-blind, placebo-controlled study. PLoS One 2014;9(8):e104175 [PubMed: 25148243].CrossRefGoogle ScholarPubMed
Adler, L, Tanaka, Y, Williams, D, Trzepacz, PT, Goto, T, Allen, AJet al.Executive function in adults with attention-deficit/hyperactivity disorder during treatment with atomoxetine in a randomized, placebo-controlled, withdrawal study. J Clin Psychopharmacol 2014;34(4):461–466. [PubMed: 24977716].CrossRefGoogle Scholar
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Text Revision (DSM-IV-TR) 4th edWashington DC: American Psychiatric Press; 2000.Google Scholar
American Psychiatric Association Diagnostic Statistical Manual of Mental Disorders (DSM-III), 3rd ed., Washington DC: American Psychiatric Press; 1980.Google Scholar
American Psychiatric Association Diagnostic Statistical Manual of Mental Disorders (DSM-5), 5th ed., Washington DC: American Psychiatric Press; 2013.Google Scholar
Anastopoulos, AD, Smith, TF, Garrett, ME, Morrissey-Kane, E, Schatz, NK, Sommer, JLet al.Self-regulation of emotion, functional impairment, and comorbidity among children with AD/HD. J Atten Disord 2011;15(7):583–592. [PubMed: 20686097].CrossRefGoogle ScholarPubMed
Asherson, PClinical assessment and treatment of attention deficit hyperactivity disorder in adults. Expert Rev Neurother 2005;5(4):525–539. [PubMed: 16026236].CrossRefGoogle ScholarPubMed
Asherson, P, Bushe, C, Saylor, K, Tanaka, Y, Deberdt, W, Upadhyaya, HJPsychopharmacol. Efficacy of atomoxetine in adults with attention deficit hyperactivity disorder: an integrated analysis of the complete database of multicenter placebo-controlled trials. J Psychopharmacol 2014;28(9):837–846. [PubMed: 25035246].CrossRefGoogle ScholarPubMed
Banaschewski, T, Jennen-Steinmetz, C, Brandeis, D, Buitelaar, JK, Kuntsi, J, Poustka, Let al.Neurpsychological correlates of emtional lability in children with ADHD. J Child Psychol Psychiatry 2012;53(11):1139–1148. [PubMed: 22882111].CrossRefGoogle Scholar
Barkley, RADeficient emotional self-regulation: a core component of attention-deficit/hyperactivity disorder. J ADHD Relat Disord 2010;1(2):5–37.Google Scholar
Barkley, RA, Fischer, MThe unique contribution of emotional impulsiveness to impairment in major life activities in hyperactive children as adults. J Am Acad Child Adolesc Psychiatry 2010;49(5):503–513. [PubMed: 20431470].Google ScholarPubMed
Barkley, RA, Murphy, KRDeficient emotional self-regulation in adults with attention-deficit/hyperactivity disorder (ADHD): the relative contributions of emotional impulsiveness and ADHD symptoms to adaptive impairments in major life activities. J ADHD Relat Disord 2010;1(4):5–28.Google Scholar
Bradley, CThe behavior of children receiving benzedrine. Am J Psychiatry 1937;94:577–585.CrossRefGoogle Scholar
Brod, M, Johnston, J, Able, S, Swindle, RValidation of the adult attention-deficit/hyperactivity disorder quality-of-life Scale (AAQoL): a disease-specific quality-of-life measure. Qual Life Res 2006;15(1):117–129. [PubMed: 16411036].CrossRefGoogle ScholarPubMed
Brown, TE, Holdnack, J, Saylor, K, Adler, L, Spencer, T, Williams, DWet al.Effect of atomoxetine on executive function impairments in adults with ADHD. J Atten Disord 2011;15(2):130–138. [PubMed: 20026871].CrossRefGoogle ScholarPubMed
Conners, CK, Erhardt, D, Sparrow, EConners’ Adult A.D.H.D. Rating Scales (CAARS). North Tonawanda NY: Multi-Health Systems Inc; 1999.Google Scholar
Durell, TM, Pumariega, AJ, Rothe, EM, Tamayo, JM, Baron, D, Williams, DEffects of open-label atomoxetine on African-American and Caucasian pediatric outpatients with attention-deficit/hyperactivity disorder. Ann Clin Psychiatry 2009;21(1):26–37. [PubMed: 19239830].Google ScholarPubMed
Durell, TM, Adler, LA, Williams, DW, Deldar, A, McGough, JJ, Glaser, PEet al.Atomoxetine treatment of attention-deficit/hyperactivity disorder in young adults with assessment of functional outcomes: a randomized, double-blind, placebo-controlled clinical trial. J Clin Psychopharmacol 2013;33(1):45–54. [PubMed: 23277268].CrossRefGoogle ScholarPubMed
Epstein, JN, Conners, CK, Erhardt, D, Arnold, LE, Hechtman, L, Hinshaw, SPet al.Familial aggregation of ADHD characteristics. J Abnorm Child Psychol 2000;28(6):585–594. [PubMed: 11104319].CrossRefGoogle ScholarPubMed
Faraone, SV, Spencer, T, Aleardi, M, Pagano, C, Biederman, JMeta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 2004;24(1):24–29. [PubMed: 14709943].CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J, Mick, EThe age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med 2006;36(2):159–165. [PubMed: 16420712].CrossRefGoogle ScholarPubMed
Fayyad, J, De Graaf, R, Kessler, R, Alonso, J, Angermeyer, M, Demyttenaere, Ket al.Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorder. Br J Psychiatry 2007;190:402–409. [PubMed: 17470954].CrossRefGoogle ScholarPubMed
Ferrer, M, Andión, O, Matalí, J, Valero, S, Navarro, JA, Ramos-Quiroga, JAet al.Comorbid attention-deficit/hyperactivity disorder in borderline patients defines an impulsive subtype of borderline personality disorder. J Pers Disord 2010;24(6):812–822. [PubMed: 21158602].CrossRefGoogle ScholarPubMed
Goto, T, Hirata, Y, Takita, Y, Trzepacz, PT, Allen, AJ, Song, DHet al.Efficacy and safety of atomoxetine hydrochloride in Asian adults with ADHD: a multinational 10-week randomized double-blind placebo-controlled Asian study. J Atten Disord 2013 [Epub ahead of print, PubMed: 24203774].Google Scholar
Guy, WECDEU Assessment Manual for Psychopharmacology, revised 1976. Rockville, MD: National Institute of Mental Health, Psychopharmacology Research Branch; 1976. p. 217–222. [313–31].Google Scholar
Hoffman, LBPostencephalitic behavior disorders in children. Bull Johns Hopkins Hosp 1922;33:372–375.Google Scholar
Hulvershorn, LA, Mennes, M, Castellanos, FX, Di Martino, A, Milham, MP, Hummer, TAet al.Abnormal amygdala functional connectivity associated with emotional lability in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2014;53(3):351–361. [PubMed: 24565362].CrossRefGoogle ScholarPubMed
Jarratt, KP, Riccio, CA, Siekierski, BMAssessment of attention deficit hyperactivity disorder (ADHD) using the BASC and BRIEF. Appl Neuropsychol 2005;12(2):83–93. [PubMed: 16083397].CrossRefGoogle ScholarPubMed
Kessler, RC, Adler, L, Barkley, R, Biederman, J, Conners, CK, Demler, Oet al.The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006;163(4):716–723. [PubMed: 16585449].CrossRefGoogle ScholarPubMed
Koesters, M, Becker, T, Kilian, R, Fegert, JM, Weinmann, SLimits of meta-analysis: methylphenidate in the treatment of adult attention-deficit hyperactivity disorder. J Psychopharmacol 2009;23(7):733–744. [PubMed: 18562416].CrossRefGoogle ScholarPubMed
Marchant, BK, Reimherr, FW, Halls, C, Williams, ED, Strong, RE, Kondo, Det al.Long-term open-label response to atomoxetine in adult ADHD: influence of sex, emotional dysregulation, and double-blind response to atomoxetine. Atten Defic Hyperact Disord 2011;3(3):237–244. [PubMed: 21442440].CrossRefGoogle ScholarPubMed
McIntyre, RS, Kennedy, SH, Soczynska, JK, Nguyen, HT, Bilkey, TS, Woldeyohannes, HOet al.Attention-deficit/hyperactivity disorder in adults with bipolar disorder or major depressive disorder: results from the international mood disorders collaborative project. Prim Care Companion J Clin Psychiatry 2010;12(3.)[PubMed: 20944770].Google ScholarPubMed
Merwood, AExploring the aetiology of ADHD: rater effects, the comorbidity with temperament and emotional lability, and polygenic scores. [PhD thesis] London: King's College; 2013.Google Scholar
Merwood, A, Chen, W, Rijsdijk, F, Skirrow, C, Larsson, H, Thapar, Aet al.Genetic associations between the symptoms of attention-deficit/hyperactivity disorder and emotional lability in child and adolescent twins. J Am Acad Child Adolesc Psychiatry 2014;53(2):209–220. [PubMed: 24472255].CrossRefGoogle ScholarPubMed
Reimherr, FW, Marchant, BK, Strong, RE, Hedges, DW, Adler, L, Spencer, TJet al.Emotional dysregulation in adult ADHD and response to atomoxetine. Biol Psychiatry 2005;58(2):125–131. [PubMed: 16038683].CrossRefGoogle ScholarPubMed
Reimherr, FW, Williams, ED, Strong, RE, Mestas, R, Soni, P, Marchant, BK:. A double-blind, placebo-controlled, crossover study of osmotic release oral system methylphenidate in adults with ADHD with assessment of oppositional and emotional dimensions of the disorder. J Clin Psychiatry 2007;68:93–101.CrossRefGoogle ScholarPubMed
Reimherr, FW, Marchant, BK, Olsen, JL, Halls, C, Kondo, DG, Williams, EDet al.Emotional dysregulation as a core feature of adult ADHD: its relationship with clinical variables and treatment response in two methylphenidate trials. J ADHD Relat Disord 2010;1(4):53–64.Google Scholar
Retz, W, Stieglitz, RD, Corbisiero, S, Retz-Junginger, P, Rösler, MEmotional dysregulation in adult ADHD: What is the empirical evidence?. Expert Rev Neurother 2012;12(10):1241–1251. [PubMed: 23082740].CrossRefGoogle ScholarPubMed
Rösler, M, Retz, W, Fischer, R, Ose, C, Alm, B, Deckert, Jet al.Twenty-four-week treatment with extended release methylphenidate improves emotional symptoms in adult ADHD. World J Biol Psychiatry 2010;11(5):709–718. [PubMed: 20353312].CrossRefGoogle ScholarPubMed
Roth, RM, Isquith, PK, Gioia, GABehavior Rating Inventory of Executive Function®–Adult Version (BRIEF®-A). Lutz, Florida: PAR Inc.; 2005.Google Scholar
Shaw, P, Stringaris, A, Nigg, J, Leibenluft, EEmotion dysregulation in attention deficit hyperactivity disorder. Am J Psychiatry 2014;171(3):276–293. [PubMed: 24480998].CrossRefGoogle ScholarPubMed
Simon, V, Czobor, P, Bálint, S, Mészáros, A, Bitter, IPrevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry 2009;194(3):204–211. [PubMed: 19252145].CrossRefGoogle ScholarPubMed
Skirrow, C, Asherson, PEmotional lability, comorbidity and impairment in adults with attention-deficit hyperactivity disorder. J Affect Disord 2013;147(1–3):80–86. [PubMed: 23218897].CrossRefGoogle ScholarPubMed
Skirrow, C, Hosang, GM, Farmer, AE, Asherson, PAn update on the debated association between ADHD and bipolar disorder across the lifespan. J Affect Disord 2012;141(2–3)|:143–159. [PubMed: 22633181].CrossRefGoogle ScholarPubMed
Skirrow, C, McLoughlin, G, Kuntsi, J, Asherson, PBehavioral, neurocognitive and treatment overlap between attention-deficit/hyperactivity disorder and mood instability. Expert Rev Neurother 2014;9(4):489–503. [PubMed: 19344301].CrossRefGoogle Scholar
Sobanski, E, Sabljic, D, Alm, B, Baehr, C, Dittmann, RW, Skopp, Get al.A randomized, waiting list-controlled 12-week trial of atomoxetine in adults with ADHD. Pharmacopsychiatry 2012;45(3):100–107. [PubMed: 22174029].Google ScholarPubMed
Still, GFSome abnormal psychical conditions in children. Lancet 1902; 1: 1008–1012. 1077–82, 1163–8].Google Scholar
Surman, CB, Biederman, J, Spencer, T, Yorks, D, Miller, CA, Petty, CRet al.Deficient emotional self-regulation adult attention deficit hyperactivity disorder: a family risk analysis. Am J Psychiatry 2011;168(6):617–623. [PubMed: 21498464].CrossRefGoogle ScholarPubMed
Surman, CB, Biederman, J, Spencer, T, Miller, CA, McDermott, KM, Faraone, SVUnderstanding deficient emotional self-regulation in adults with attention deficit hyperactivity disorder: a controlled study. Atten Defic Hyperact Disord 2013;5(3):273–281. [PubMed: 23413201].CrossRefGoogle ScholarPubMed
Takahashi, M, Goto, T, Takita, Y, Chung, SK, Wang, Y, Gau, SSOpen-label, dose-titration tolerability study of atomoxetine hydrochloride in Korean, Chinese, and Taiwanese adults with attention-deficit/hyperactivity disorder. Asia Pac Psychiatry 2014;6(1):62–70. [PubMed: 23857916].CrossRefGoogle ScholarPubMed
Tamayo, JM, Pumariega, A, Rothe, EM, Kelsey, D, Allen, AJ, Vélez-Borrás, Jet al.Latino versus Caucasian response to atomoxetine in attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 2008;18(1):44–53. [PubMed: 18294088].CrossRefGoogle ScholarPubMed
Upadhyaya, H, Adler, LA, Casas, M, Kutzelnigg, A, Williams, D, Tanaka, Yet al.Baseline characteristics of European and non-European adult patients with attention deficit hyperactivity disorder participating in a placebo-controlled, randomized treatment study with atomoxetine. Child Adolesc Psychiatry Ment Health 2013;7(1):14 [PubMed: 23648011].CrossRefGoogle Scholar
Wingo, AP, Ghaemi, SNA systematic review of rates and diagnostic validity of comorbid adult attention-deficit/hyperactivity disorder and bipolar disorder. J Clin Psychiatry 2007;68(11):1776–1784. [PubMed: 18052572].CrossRefGoogle ScholarPubMed
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