Abstract
Adult ADHD is a frequent psychiatric disorder affecting relevant aspects of an individual’s life. The aim of our study group was to carry out the first randomized controlled multicenter study to evaluate the effects of psychotherapy compared to clinical management in combination with psychopharmacological treatment with methylphenidate (MPH) or placebo (Plac) in a factorial four-arm design. Here, we present the enrollment procedure and description of adult ADHD patients recruited for the trial. Four hundred and thirty-three adult patients with ADHD were randomized at seven study sites in Germany to four treatment conditions: manualized dialectical-behavioral-therapy-based group psychotherapy (GPT) plus MPH or Plac, or clinical management (CM) including supportive counseling plus MPH or Plac with weekly sessions in the first 12 weeks and monthly sessions thereafter. Assessment for eligibility included standardized scales and instruments. After prescreening of 1,480 patients, 518 were evaluated for trial participation and 433 were randomized. The main reasons for prescreening failure were lack of interest in participating (n = 205), difficulties in meeting the time and effort requirements for participation (n = 186), and contraindications for psychopharmacological treatment with MPH (n = 194). The full analysis set (FAS) comprised 419 adult ADHD patients (mean age 35.2 years, males/females 1:1). Fifty-seven percent of the patients suffered from the combined ADHD subtype. Prevalence of at least one current or lifetime axis-I comorbidity was 66 %. Axis-II comorbidity rates was 18 % (patients with comorbid borderline and antisocial personality disorders were excluded). Our network was able to recruit an adult ADHD sample essentially comparable to community samples. A selection bias was created by excluding patients unable or unwilling to participate, or who had somatic and psychiatric contraindications for stimulant treatment (Current Controlled Trials ISRCTN54096201, Funding: Federal Ministry of Education and Research 01GV0606).
Similar content being viewed by others
References
Biederman J (2004) Impact of comorbidity in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry 65(Suppl. 3):3–7
Bramham J, Young S, Bickerdike A, Spain D, McCartan D, Xenitidis K (2008) Evaluation of group cognitive behavioral therapy for adults with ADHD. J Atten Disord 12(5):434–441
Buitelaar JK, Kooij JJ, Ramos-Quiroga JA, Dejonckheere J, Casas M, van Oene JC, Schäuble B, Trott GE (2011) Predictors of treatment outcome in adults with ADHD treated with OROS® methylphenidate. Prog Neuropsychopharmacol Biol Psychiatry 35(2):554–560
Carpenter JR, Roger JH, Kenward MG (2012) Analysis of longitudinal trials with protocol deviation: a framework for relevant, accessible assumptions, and inference via multiple imputation. (in press with Journal of Biopharmaceutical Statistics, due to appear in issue 6 (November/December) in volume 23 (2013))
Castells X, Ramos-Quiroga JA, Rigau D, Bosch R, Nogueira M, Vidal X, Casas M (2011) Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis. CNS Drugs 25(2):157–169
Cumyn L, French L, Hechtman L (2009) Comorbidity in adults with attention-deficit hyperactivity disorder. Can J Psychiatry 54(10):673–683
de Zwaan M, Gruss B, Müller A, Graap H, Martin A, Glaesmer H, Hilbert A, Philipsen A (2012) The estimated prevalence and correlates of adult ADHD in a German community sample. Eur Arch Psychiatry Clin Neurosci 262(1):79–86
Ebert D, Krause J, Roth-Sackenheim C (2003) ADHD in adulthood-guidelines based on expert consensus with DGPPN support. Nervenarzt 74:939–946
Emilsson B, Gudjonsson G, Sigurdsson JF, Baldursson G, Einarsson E, Olafsdottir H, Young S (2011) Cognitive behaviour therapy in medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. BMC Psychiatry 11:116
Faraone SV, Spencer T, Aleardi M, Pagano C, Biederman J (2004) Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 24(1):24–29
Fayyad J, De Graaf R, Kessler R, Alonso J, Angermeyer M, Demyttenaere K, De Girolamo G, Haro JM, Karam EG, Lara C, Lépine JP, Ormel J, Posada-Villa J, Zaslavsky AM, Jin R (2007) Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorder. Br J Psychiatry 190:402–409
Hesslinger B, Tebartz van Elst L, Nyberg E, Dykierek P, Richter H, Berner M, Ebert D (2002) Psychotherapy of attention deficit hyperactivity disorder in adults: a pilot study using a structured skills training program. Eur Arch Psychiatry Clin Neurosci 252(4):177–184
Hesslinger B, Philipsen A, Richter H (2004) Psychotherapy in adult ADHD: a workbook. Hogrefe Verlag, Goettingen
Hirvikoski T, Waaler E, Alfredsson J, Pihlgren C, Holmström A, Johnson A, Rück J, Wiwe C, Bothén P, Nordström AL (2011) Reduced ADHD symptoms in adults with ADHD after structured skills training group: results from a randomized controlled trial. Behav Res Ther 49(3):175–185
Jacob CP, Romanos J, Dempfle A, Heine M, Windemuth-Kieselbach C, Kruse A, Reif A, Walitza S, Romanos M, Strobel A, Brocke B, Schäfer H, Schmidtke A, Böning J, Lesch KP (2007) Co-morbidity of adult attention-deficit/hyperactivity disorder with focus on personality traits and related disorders in a tertiary referral center. Eur Arch Psychiatry Clin Neurosci 257(6):309–317
Jans T, Philipsen A, Graf E, Ihorst G, Gerlach M, Warnke A (2009) Does the treatment of maternal attention deficit and hyperactivity disorder (ADHD) enhance the efficacy of a behavioural parent training for the treatment of their children’s ADHD? Study protocol of a randomized controlled multicentre trail. Atten Defic Hyperact Disord 1(1):33–45
Jans T, Graf E, Jacob C, Zwanzger U, Groß-Lesch S, Matthies S, Perlov E, Hennighausen K, Jung M, Rösler M, Schulte-Altedorneburg M, von Gontard A, Hänig S, Sobanski E, Alm B, Poustka L, Bliznak L, Colla M, Gentschow L, Burghardt R, Salbach-Andrae H, Becker K, Holtmann M, Freitag C, Warnke A, Philipsen A (2013) A randomized controlled multicentre trial on the treatment for ADHD in mothers and children: enrolment and basic characteristics of the study sample. Atten Defic Hyperact Disord 5(1):29–40
Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Faraone SV, Greenhill LL, Howes MJ, Secnik K, Spencer T, Ustun TB, Walters EE, Zaslavsky AM (2006) The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 163(4):716–723
Lindemann C, Langner I, Kraut AA, Banaschewski T, Schad-Hansjosten T, Petermann U, Petermann F, Schreyer-Mehlhop I, Garbe E, Mikolajczyk RT (2012) Age-specific prevalence, incidence of new diagnoses, and drug treatment of attention-deficit/hyperactivity disorder in Germany. J Child Adolesc Psychopharmacol 22(4):307–314
Manuzza S, Klein RG, Bessler A, Malloy P, LaPadula M (1998) Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry 155(4):493–498
Matthies S, van Elst LT, Feige B, Fischer D, Scheel C, Krogmann E, Perlov E, Ebert D, Philipsen A (2011) Severity of childhood attention-deficit hyperactivity disorder–a risk factor for personality disorders in adult life? J Pers Disord 25(1):101–114
Mongia M, Hechtman L (2012) Cognitive behavior therapy for adults with attention-deficit/hyperactivity disorder: a review of recent randomized controlled trials. Curr Psychiatry Rep 14(5):561–567
Pérez de Los Cobos J, Siñol N, Pérez V, Trujols J (2012) Pharmacological and clinical dilemmas of prescribing in co-morbid adult attention-deficit/hyperactivity disorder and addiction. Br J Clin Pharmacol [Epub ahead of print]
Philipsen A (2012) Psychotherapy in adult attention deficit hyperactivity disorder: implications for treatment and research. Expert Rev Neurother 12(10):1217–1225
Philipsen A, Richter H, Peters J, Alm B, Sobanski E, Colla M, Münzebrock M, Scheel C, Jacob C, Perlov E, Tebartz van Elst L, Hesslinger B (2007) Structured group psychotherapy in adults with attention deficit hyperactivity disorder: results of an open multicenter study. J Nerv Ment Dis 195(12):1013–1019
Philipsen A, Graf E, Tebartz van Elst L, Jans T, Warnke A, Hesslinger B, Ebert D, Gerlach M, Matthies S, Colla M, Jacob C, Sobanski E, Alm B, Rösler M, Ihorst G, Gross-Lesch S, Gentschow L, Kis B, Huss M, Lieb K, Schlander M, Berger M (2010) Evaluation of the efficacy and effectiveness of a structured disorder tailored psychotherapy in ADHD in adults: study protocol of a randomized controlled multicentre trial. Atten Defic Hyperact Disord 2(4):203–211
Rösler M, Fischer R, Ammer R, Ose C, Retz W (2009) A randomised, placebo-controlled, 24-week, study of low-dose extended-release methylphenidate in adults with attention-deficit/hyperactivity disorder. Eur Arch Psychiatry Clin Neurosci 259(2):120–129
Rösler M, Casas M, Konofal E, Buitelaar J (2010) Attention deficit hyperactivity disorder in adults. World J Biol Psychiatry 11(5):684–698
Rostain AL, Ramsay JR (2006) A combined treatment approach for adults with ADHD–results of an open study of 43 patients. J Atten Disord 10:150–159
Safren SA, Otto MW, Sprich S, Winett CL, Wilens TE, Biederman J (2005) Cognitive-behavioral therapy for ADHD in medication-treated adults with continued symptoms. Behav Res Ther 43(7):831–842
Safren SA, Sprich S, Mimiaga MJ, Surman C, Knouse L, Groves M, Otto MW (2010) Cognitive behavioral therapy vs relaxation with educational support for medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. JAMA 304(8):875–880
Salakari A, Virta M, Grönroos N, Chydenius E, Partinen M, Vataja R, Kaski M, Iivanainen M (2010) Cognitive-behaviorally-oriented group rehabilitation of adults with ADHD: results of a 6-month follow-up. J Atten Disord 13(5):516–523
Sobanski E, Brüggemann D, Alm B, Kern S, Philipsen A, Schmalzried H, Hesslinger B, Waschkowski H, Rietschel M (2008) Subtype differences in adults with attention-deficit/hyperactivity disorder (ADHD) with regard to ADHD-symptoms, psychiatric comorbidity and psychosocial adjustment. Eur Psychiatry 23(2):142–149
Solanto MV, Marks DJ, Wasserstein J, Mitchell K, Abikoff H, Alvir JM, Kofman MD (2010) Efficacy of meta-cognitive therapy of adult ADHD. Am J Psychiatry 167(8):958–968
Spencer TJ, Biederman J, Wilens TE, Faraone SV (2002) Overview and neurobiology of attention-deficit/hyperactivity disorder. J Clin Psychiatry 63(Suppl. 12):3–9
Statistisches Bundesamt (Federal Statistical Office) (2009) Statistisches Jahrbuch 2009 für die Bundesrepublik Deutschland (Statistical Yearbook 2009 for the Federal Republic of Germany). Statistisches Bundesamt, Wiesbaden
Stevenson CS, Whitmont S, Bornholt L, Livesey D, Stevenson RJ (2002) A cognitive remediation programme for adults with attention deficit hyperactivity disorder. Aust N Z J Psychiatry 36(5):610–616
Surman CB, Monuteaux MC, Petty CR, Faraone SV, Spencer TJ, Chu NF, Biederman J (2010) Representativeness of participants in a clinical trial for attention-deficit/hyperactivity disorder? Comparison with adults from a large observational study. J Clin Psychiatry 71(12):1612–1616
Virta M, Vedenpää A, Grönroos N, Chydenius E, Partinen M, Vataja R, Kaski M, Iivanainen M (2008) Adults with ADHD benefit from cognitive-behaviorally oriented group rehabilitation: a study of 29 participants. J Atten Disord 12(3):218–226
Weiss M, Hechtman L (2006) Adult ADHD Research Group. A randomized double-blind trial of paroxetine and/or dextroamphetamine and problem-focused therapy for attention-deficit/hyperactivity disorder in adults. J Clin Psychiatry 67(4):611–619
Weiss M, Murray C, Wasdell M, Greenfield B, Giles L, Hechtman L (2012) A randomized controlled trial of CBT therapy for adults with ADHD with and without medication. BMC Psychiatry 12:30
Wilens TE, Dodson W (2004) A clinical perspective of attention-deficit/hyperactivity disorder into adulthood. J Clin Psychiatry 65(10):1301–1313
Williams ED, Reimherr FW, Marchant BK, Strong RE, Halls C, Soni P, Gale PD, Robison RJ (2010) Personality disorder in ADHD Part 1: assessment of personality disorder in adult ADHD using data from a clinical trial of OROS methylphenidate. Ann Clin Psychiatry 22(2):84–93
Wittchen HU, Zaudig M, Fydrich T (1997) SKID: Strukturiertes Klinisches Interview für DSM IV. Achse I und II, Hogrefe
Young S, Amarasinghe JM (2010) Practitioner review: non-pharmacological treatments for ADHD: a lifespan approach. J Child Psychol Psychiatry 51(2):116–133
Zylowska L, Ackerman DL, Yang MH, Futrell JL, Horton NL, Hale TS, Pataki C, Smalley SL (2008) Mindfulness meditation training in adults and adolescents with ADHD: a feasibility study. J Atten Disord 11(6):737–746
Acknowledgments
Our network on psychotherapy of ADHD is supported by the German Federal Ministry of Education and Research (BMBF; 01GV0605, 01GV0606) within the framework research networks on psychotherapy. Furthermore, we want to thank all members of COMPAS teams at the study sites: Wuerzburg: PD C. Jacob, Dr. T. Jans, Dr. S. Groß-Lesch, M. Heine, A. Boreatti-Hümmer, J. Heupel, S. Reichert, S. Müller, S. Kreiker, A. Gessner, A. Conzelmann, and C. Bähne; Berlin: Dr. M. Colla, L. Gentschow, P. Kunze, and D. Langner; Mannheim: PD Dr. E. Sobanski, Dr. B. Alm, M. Schumacher-Stien, S. Bukow, and S. Argiriou-Martin; Homburg: Prof. Dr. M. Rösler, Prof. Dr. Wofgang Retz, PD Dr. P. Retz-Junginger, Dr. K. Römer, Dr. B. Leipnitz, Dr. S Doyran, and Dr. M. Schulte-Altedorneburg; Essen: Dr. Kis, Dr. M. Abdel-Hamid, V. Heinrich, PD Dr. M. Krämer, and PD Dr. J. Uekermann; Mainz: Prof. Dr. M. Huss, C. Kornmann, A. Bürger, G. Chervenkova, and P. Meinhardt; Freiburg: Prof. Dr. A. Philipsen, Dr. E. Graf, Dr. S. Matthies, Dr. M. Löwer, P. Borel, I. Jansen, S. Bonfico, M. Jooßens, C. Sadohara, M. Weber, M. Kamp, T. Dopatka, Dr. E. Perlov, and Dr. G. Ihorst; and Lörrach: Dr. C. Carl and Dr. C. Keutler. We thank Medice Arzneimittel Puetter GmbH & Co. KG for providing the trial medication (Medikinet retard licensed as Medikinet adult and matching placebo) and particularly Dr. R. Fischer for his advice in preparing the study protocol and his assistance in SAE management. We gratefully thank all participating patients for their cooperation.
Conflict of interest
A. Philipsen: advisory boards, lectures, phase III studies or travel grants within the last 3 years: Eli Lilly, Janssen-Cilag, Medice Arzneimittel Pütter GmbH, Novartis, and Shire, she is an author of books or articles on psychotherapy published by Elsevier, Hogrefe, Schattauer, Kohlhammer, and Karger publishers; E. Graf: none; T. Jans: none; S. Matthies: none; P. Borel: none; M. Colla: advisory boards, speaker’s honoraria or phase III studies within the last 3 years: Shire, Eli Lilly, and Novartis; L. Gentschow: none; D. Langner: none; C. Jacob received speaker’s honoraria by Medice and is member of the advisory boards of Medice; S. Groß-Lesch: none; E. Sobanski: advisory boards, IITs, lectures or Phase III studies within the last 3 years: Medice, Shire, Eli Lilly, and Novartis; B. Alm: advisory boards, lectures or phase III studies within the last 3 years: Medice, Eli Lilly; M. Schuhmacher-Stien: none; M. Rösler is member of the speakers bureau of Medice, Janssen, and Shire; he is a member of the advisory boards of Lilly, Shire, Medice, and Janssen. He performed clinical trials for Medice and Lilly; P. Retz-Junginger received salaries from Hogrefe Publishers; W. Retz received speaker’s honoraria by Medice, is member of the advisory boards of Novartis and Medice, has been involved in clinical trials conducted by BMBF, Vifor, Novartis, and Medice, and is an author of manuals, handbooks, and diagnostic tools published by Hogrefe, Springer, Kohlhammer, and Karger publishers; B. Kis received travel grants by Servier Deutschland GmbH and speaker’s honoraria by Medice and Servier Deutschland GmbH, is a member of the advisory boards of Medice and Novartis Pharma GmbH, and has been involved in clinical trials conducted by Eli Lilly/Lilly Deutschland GmbH; M. Abdel-Hamid: none; V. Heinrich has been involved in clinical trials conducted by Eli Lilly/Lilly Deutschland GmbH; M. Huss: within the past 3 years, he received speaker honoraria from Eli Lilly, Janssen-Cilag, Medice, Novartis, and Shire, he is principal investigator of phase II study sponsored by Lundbeck, principal investigator of several phase III studies sponsored by Shire and Novartis, and principal investigator/sponsor of three IIT studies (investigator initiated trials, phase III and IV) in unrestricted cooperation with Engelhardt Arzneimittel, Steiner Arzneimittel, and Medice; he worked as consultant for Engelhardt, Medice, Shire, and Steiner Arzneimittel and member in the Advisory boards of Eli Lilly, Medice, Novartis, and Shire; C. Kornmann: none; A. Bürger received travel grants by MSAGD in RLP (Ministerium für Soziales, Arbeit, Gesundheit und Demografie) and MBWWK in RLP (Ministerium für Bildung, Wissenschaft, Weiterbildung und Kultur); L. Tebartz van Elst received travel grants by Medtronic, Janssen, Otsuka, Lilly, and SCS and speaker’s honoraria by Otsuka, SCS, Lilly, Medtronic, and Janssen-Cilag; M. Berger: none.
Author information
Authors and Affiliations
Corresponding author
Additional information
This study was conducted by the Comparison of Methylphenidate and Psychotherapy Study (COMPAS) group.
Please refer to the “Appendix” section for COMPAS group members.
Appendix
Appendix
Members of the COMPAS study group (Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study; coordinating investigator: Prof. Dr. A. Philipsen, Department of Psychiatry and Psychotherapy, Freiburg University Medical Center, Director: Prof. Dr. M. Berger) are our colleagues at the study sites at Wuerzburg (Wuerzburg University Hospital, Department of Psychiatry, Psychosomatics and Psychotherapy, Director: Prof. Dr. J. Deckert; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Director: Prof. Dr. A. Warnke), Berlin (Charité–University Medicine, Campus Benjamin Franklin, Department of Psychiatry and Psychotherapy, Director: Prof. Dr. I. Heuser), Mannheim (Central Institute for Mental Health, Clinic for Psychiatry and Psychotherapy, Director: Prof. Dr. A. Meyer-Lindenberg), Homburg (Saarland University Hospital and Saarland University Faculty of Medicine, Institute for Forensic Psychology and Psychiatry, Director: Prof. Dr. M. Roesler), Essen (LVR-Hospital Essen, Department for Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Director: Prof. Dr. J. Wiltfang), Mainz (University Medicine Mainz, Clinic for Child and Adolescent Psychiatry and Psychotherapy, Director: Prof. Dr. M. Huss), Lörrach (St. Elisabethen Krankenhaus, Department of Child and Adolescent Psychiatry and Psychotherapy, Director: Dr. C. Keutler), members of the Clinical Trials Unit at University Medical Center Freiburg (Director: R. Bredenkamp) as well as members of the Data Monitoring and Safety Committee (Prof. Dr. Dr. H. Remschmidt, Prof. Dr. G. Wassmer, and PD Dr. N. Wodarz). Independent supervision is carried out at the Institute for Psychology of Freiburg University (Dr. U. Frank) in cooperation with colleagues in private practice (Dr. F. Mayer-Bruns, K. Schehr). Other projects in our network on psychotherapy research in ADHD (speaker: Prof. A. Philipsen, Freiburg University Medical Center & Prof. Dr. A. Warnke, Wuerzburg University Hospital) are coordinated by Dr. T. Jans (Wuerzburg University Hospital, AIMAC (ADHD in mothers and children)), Prof. Dr. L. Tebartz van Elst (University Medical Center Freiburg, functional and morphometric brain mapping), and Prof. Dr. K.P. Lesch (Wuerzburg University Hospital, molecular genetics).
Rights and permissions
About this article
Cite this article
Philipsen, A., Graf, E., Jans, T. et al. A randomized controlled multicenter trial on the multimodal treatment of adult attention-deficit hyperactivity disorder: enrollment and characteristics of the study sample. ADHD Atten Def Hyp Disord 6, 35–47 (2014). https://doi.org/10.1007/s12402-013-0120-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12402-013-0120-z