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Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine

Published online by Cambridge University Press:  24 October 2015

E. Sobanski ,
S. Leppämäki ,
C. Bushe ,
L. Berggren ,
M. Casillas  and
W. Deberdt
E. Sobanski*
Affiliation:
Central Institute of Mental Health Mannheim, Medical Faculty Mannheim, University of Heidelberg, J5, 68159Mannheim, Germany
S. Leppämäki
Affiliation:
Finnish Institute of Occupational Health, PL40, FIN-00250 Helsinki, Finland Department of Psychiatry, Helsinki University Central Hospital, PL590, FIN-00250 HUS, Helsinki, Finland
C. Bushe
Affiliation:
Medical Department, Eli Lilly & Co. Ltd, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey, GU20 6PH, United Kingdom
L. Berggren
Affiliation:
Global Statistical Sciences, Lilly Deutschland GmbH, Werner Reimers Str. 2-4, 61350Bad Homburg, Germany
M. Casillas
Affiliation:
Medical Department, Lilly S.A., Avenida de la Industria, 30, 28108 Alcobendas, Madrid, Spain
W. Deberdt
Affiliation:
Medical Department, S.A Eli Lilly Benelux N.V., Markiesstraat 1/4B, B - 1000Brussel, Belgium
*
⁎Corresponding author. Tel.: +49 0 621 1703 2852. E-mail address:Esther.Sobanski@zi-mannheim.de (E. Sobanski).
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Abstract

Background

Atomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns.

Methods

From 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24 weeks; n = 1443) and/or short-term (12 weeks; n = 2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling.

Results

Based on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12 weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e. ≥ 30% reduction in CAARS-Inv:SV total score, and CGI-S score ≤ 3) were observed at 8 and 24 weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4.

Conclusions

While many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24 weeks. Longer-term treatment may be associated with greater numbers of responders.

Keywords

ADHDLong-termResponsePatternsClustersAtomoxetine
Type
Original article
Information
European Psychiatry , Volume 30 , Issue 8 , November 2015 , pp. 1011 - 1020
Copyright
Copyright © European Psychiatric Association 2020

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References

Able, S.L.Johnston, J.A.Adler, L.A.Swindle, R.W.. Functional and psychosocial impairment in adults with undiagnosed ADHD. Psychol Med 2007;37(1):97–107.CrossRefGoogle ScholarPubMed
Adler, L.Cohen, J.. Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder. Psychiatr Clin North Am 2004;27(2):187–201.CrossRefGoogle ScholarPubMed
Adler, L.Dietrich, A.Reimherr, F.W.Taylor, L.V.Sutton, V.K.Bakken, R., et al.Safety and tolerability of once versus twice daily atomoxetine in adults with ADHD. Ann Clin Psychiatry 2006;18(2):107–113.CrossRefGoogle ScholarPubMed
Adler, L.A.Spencer, T.J.Levine, L.R.Ramsey, J.L.Tamura, R.Kelsey, D., et al.Functional outcomes in the treatment of adults with ADHD. J Atten Disord 2008;11(6):720–727.CrossRefGoogle ScholarPubMed
Adler, L.A.Liebowitz, M.Kronenberger, W.Qiao, M.Rubin, R.Hollandbeck, M., et al.Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorder. Depress Anxiety 2009;26(3):212–221.CrossRefGoogle ScholarPubMed
Adler, L.A.Spencer, T.Brown, T.E.Holdnack, J.Saylor, K.Schuh, K., et al.Once-daily atomoxetine for adult attention-deficit/hyperactivity disorder: a 6-month, double-blind trial. J Clin Psychopharmacol 2009;29(1):44–50.CrossRefGoogle ScholarPubMed
Asherson, P.Bushe, C.Saylor, K.Tanaka, Y.Deberdt, W.Upadhyaya, H.. 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.CrossRefGoogle ScholarPubMed
Barbaresi, W.J.Colligan, R.C.Weaver, A.L.Voigt, R.G.Killian, J.M.Katusic, S.K.. Mortality, ADHD, and psychosocial adversity in adults with childhood ADHD: a prospective study. Pediatrics 2013;131(4):637–644.CrossRefGoogle ScholarPubMed
Biederman, J.Spencer, T.J.Wilens, T.E.Weisler, R.H.Read, S.C.Tulloch, S.J.. Long-term safety and effectiveness of mixed amphetamine salts extended release in adults with ADHD. CNS Spectrum 2005;10(12 Suppl. 20):16–25.CrossRefGoogle ScholarPubMed
Biederman, J.Faraone, S.V.Spencer, T.J.Mick, E.Monuteaux, M.C.Aleardi, M.. Functional impairments in adults with self-reports of diagnosed ADHD: a controlled study of 1001 adults in the community. J Clin Psychiatry 2006;67(4):524–540.CrossRefGoogle Scholar
Biederman, J.Petty, C.R.Clarke, A.Lomedico, A.Faraone, S.V.. Predictors of persistent ADHD: an 11-year follow-up study. J Psychiatr Res 2011;45(2):150–155.CrossRefGoogle Scholar
Biederman, J.Petty, C.R.O’Connor, K.B.Hyder, L.L.Faraone, S.V.. Predictors of persistence in girls with attention deficit hyperactivity disorder: results from an 11-year controlled follow-up study. Acta Psychiatr Scand 2012;125(2):147–156.CrossRefGoogle ScholarPubMed
Brams, M.Weisler, R.Findling, R.L.Gasior, M.Hamdani, M.Ferreira-Cornwell, M.C., et al.Maintenance of efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: randomized withdrawal design. J Clin Psychiatry 2012;73(7):977–983.CrossRefGoogle ScholarPubMed
Bushe, C.J.Savill, N.C.. Systematic review of atomoxetine data in childhood and adolescent attention-deficit hyperactivity disorder 2009–2011: focus on clinical efficacy and safety. J Psychopharmacol 2014;28(3):204–211.CrossRefGoogle ScholarPubMed
Canadian Attention Deficit Hyperactivity Disorder Resource Alliance (CADDRA). Canadian ADHD practice guidelines. 4th ed.Toronto ON: CADDRA; 2011.Google Scholar
Chang, Z.Lichtenstein, P.D’Onofrio, B.M.Sjölander, A.Larsson, H.. Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication: a population-based study. JAMA Psychiatry 2014;71(3):319–325.CrossRefGoogle ScholarPubMed
Das, D.Cherbuin, N.Butterworth, P.Anstey, K.J.Easteal, S.. A population-based study of attention deficit/hyperactivity disorder symptoms and associated impairment in middle-aged adults. PLoS One 2012;7(2):e31500.CrossRefGoogle ScholarPubMed
Dickson, R.A.Maki, E.Gibbins, C.Gutkin, S.W.Turgay, A.Weiss, M.D.. Time courses of improvement and symptom remission in children treated with atomoxetine for attention-deficit/hyperactivity disorder: analysis of Canadian open-label studies. Child Adolesc Psychiatry Ment Health 2011;5(14.CrossRefGoogle ScholarPubMed
Durell, T.M.Adler, L.A.Williams, D.W.Deldar, A.McGough, J.J.Glaser, P.E., et 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.CrossRefGoogle ScholarPubMed
Eli Lilly & Co. Strattera®. Summary of product characteristics. [Available at: http://www.medicines.org.uk/emc/medicine/14482 (updated June 2015; accessed 17 August 2015)].Google Scholar
Epstein, J.Johnson, D.Conners, C.K.Conners’ Adult ADHD Diagnostic Interview for DSM-IV (CAADID). New York: Multi Health Systems Inc.; 1999.Google Scholar
Faraone, S.V.Asherson, P.Banaschewski, T.Biederman, J.Buitelaar, J.K.Ramos-Quiroga, J.A., et al.Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers 2015. 10.1038/nrdp.2015.20.CrossRefGoogle ScholarPubMed
Fredriksen, M.Halmøy, A.Faraone, S.V.Haavik, J.. Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: a review of controlled and naturalistic studies. Eur Neuropsychopharmacol 2013;23(6):508–527.CrossRefGoogle ScholarPubMed
Goodman, D.W.. Sustained treatment effect in attention-deficit/hyperactivity disorder: focus on long-term placebo-controlled randomized maintenance withdrawal and open-label studies. Ther Clin Risk Manag 2013;9:121–130.CrossRefGoogle ScholarPubMed
Goto, T.Hirata, Y.Takita, Y.Trzepacz, P.T.Allen, A.J.Song, D.H., et 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. http://dx.doi.org/10.1177/1087054713510352 [PMID: 24203774].Google Scholar
Hirata, Y.Goto, T.Takita, Y.Trzepacz, P.T.Allen, A.J.Ichikawa, H., et al.Long-term safety and tolerability of atomoxetine in Japanese adults with attention deficit hyperactivity disorder. Asia Pac Psychiatry 2014;6(3):292–301.CrossRefGoogle ScholarPubMed
Kessler, R.C.Green, J.G.Adler, L.A.Barkley, R.A.Chatterji, S.Faraone, S.V., et al.Structure and diagnosis of adult attention-deficit/hyperactivity disorder: analysis of expanded symptom criteria from the Adult ADHD Clinical Diagnostic Scale. Arch Gen Psychiatry 2010;67(11):1168–1178.CrossRefGoogle ScholarPubMed
Kooij, S.J.Bejerot, S.Blackwell, A.Caci, H.Casas-Brugué, M.Carpentier, P.J., et al.European consensus statement on diagnosis and treatment of adult ADHD: the European Network Adult ADHD. BMC Psychiatry 2010;10:67.CrossRefGoogle ScholarPubMed
Lara, C.Fayyad, J.de Graaf, R.Kessler, R.C.Aguilar-Gaxiola, S.Angermeyer, M., et al.Childhood predictors of adult attention-deficit/hyperactivity disorder: results from the World Health Organization World Mental Health Survey Initiative. Biol Psychiatry 2009;65(1):46–54.CrossRefGoogle ScholarPubMed
Lichtenstein, P.Halldner, L.Zetterqvist, J.Sjölander, A.Serlachius, E.Fazel, S., et al.Medication for attention deficit-hyperactivity disorder and criminality. N Engl J Med 2012;367(21):2006–2014.CrossRefGoogle ScholarPubMed
Marchant, B.K.Reimherr, F.W.Halls, C.Williams, E.D.Strong, R.E.Kondo, D., et 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.CrossRefGoogle ScholarPubMed
Matza, L.S.Paramore, C.Prasad, M.. A review of the economic burden of ADHD. Cost Eff Resour Alloc 2005;3:5.CrossRefGoogle ScholarPubMed
Matza, L.S.Johnston, J.A.Faries, D.E.Malley, K.G.Brod, M.. Responsiveness of the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life Scale (AAQoL). Qual Life Res 2007;6(9):1511–1520.CrossRefGoogle Scholar
Medicines, Healthcare Products Regulatory Agency (MHRA). Public assessment report. Strattera®. 2013. [Available at: http://www.webarchive.nationalarchives.gov.uk/20141205150130/ http://www.mhra.gov.uk/home/groups/pl-a/documents/websiteresources/con020684.pdf (accessed 02 February 2015)]Google Scholar
National Institute for Health and Care Excellence (NICE). Attention deficit hyperactivity disorder: diagnosis and management of ADHD in children, young people and adults, Clinical guideline 72. 2008. [Available at: http://www.nice.org.uk/guidance/cg72 (updated November 2011; accessed 02 July 2014)].Google Scholar
Pliszka, S.R.Pharmacologic treatment of attention-deficit/hyperactivity disorder: efficacy, safety and mechanisms of action. Neuropsychol Rev 2007;17(1):61–72.CrossRefGoogle ScholarPubMed
Powers, R.L.Marks, D.J.Miller, C.J.Newcorn, J.H.Halperin, J.M.Stimulant treatment in children with attention-deficit/hyperactivity disorder moderates adolescent academic outcome. J Child Adolesc Psychopharmacol 2008;18(5):449–459.CrossRefGoogle ScholarPubMed
Reimherr, F.Amsterdam, J.Dunner, D.Adler, L.Zhang, S.Williams, D., et al.Genetic polymorphisms in the treatment of depression: speculations from an augmentation study using atomoxetine. Psychiatry Res 2010;175(1–2):67–73.CrossRefGoogle ScholarPubMed
Rösler, M.Fischer, R.Ammer, R.Ose, C.Retz, W.A randomized, placebo-controlled, 24-week, study of low-dose extended-release methylphenidate in adults with attention-deficit/hyperactivity disorder. Eur Arch Psychiatry Clin Neurosci 2009;259(2):120–129.CrossRefGoogle ScholarPubMed
Shaw, M.Hodgkins, P.Caci, H.Young, S.Kahle, J.Woods, A.G., et al.A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment. BMC Med 2012;10(1):99.CrossRefGoogle ScholarPubMed
Takahashi, M.Takita, Y.Goto, T.Ichikawa, H.Saito, K.Matsumoto, H., et al.An open-label, dose-titration tolerability study of atomoxetine hydrochloride in Japanese adults with attention-deficit/hyperactivity disorder. Psychiatry Clin Neurosci 2011;65(1):55–63.CrossRefGoogle ScholarPubMed
Takahashi, M.Goto, T.Takita, Y.Chung, S.K.Wang, Y.Gau, S.S.Open-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.CrossRefGoogle ScholarPubMed
Upadhyaya, H.Adler, L.A.Casas, M.Kutzelnigg, A.Williams, D.Tanaka, Y., et 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.CrossRefGoogle Scholar
Upadhyaya, H.Ramos-Quiroga, A.Adler, L.A.Williams, D.Tanaka, Y.Lane, J.R., et al.Maintenance of response after open-label treatment with atomoxetine hydrochloride in international European and non-European adult outpatients with attention deficit/hyperactivity disorder: a placebo-controlled, randomized withdrawal study. Eur J Psychiatry 2013;27:185–205.CrossRefGoogle Scholar
Wilens, T.E.Adler, L.A.Weiss, M.D.Michelson, D.Ramsey, J.L.Moore, R.J., et al.Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders. Drug Alcohol Depend 2008;96(1–2):145–154.CrossRefGoogle ScholarPubMed
Wilens, T.E.Adler, L.A.Tanaka, Y.Xiao, F.D'Souza, D.N.Gutkin, S.W., et al.Correlates of alcohol use in adults with ADHD and comorbid alcohol use disorders: exploratory analysis of a placebo-controlled trial of atomoxetine. Curr Med Res Opin 2011;27(12):2309–2320.CrossRefGoogle ScholarPubMed
Young, J.L.Sarkis, E.Qiao, M.Wietecha, L.Once-daily treatment with atomoxetine in adults with attention-deficit/hyperactivity disorder: a 24-week, randomized, double-blind, placebo-controlled trial. Clin Neuropharmacol 2011;34(2):51–60.Google ScholarPubMed
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