2.  What is ADHD?  A chronic disorder  Begin during early childhood and continues to adolescence  Can be full or partial clinical picture in 60% of patients during adulthood

3.  Major syndromes defines by DSM IV:  Attention disorder  Hyperactivity  Impulsivity  Different concepts was defined by:  CAARS (Conners Adult ADHD Rating Scales, Conners et al. 1999)  BAADS (Brown Adult Attention Disorder Scales, Brown 1996)  Utah criteria of adult ADHD (P. Wender, 1995)

4. Hypothesis: co-occuring emotional symptoms accompany those 3 major syndromes can be detected  Inattention, hyperactivity and impulsivity are lifelong and chronic dimension, while others emotional symptoms (eg: poor temper control, affective lability, emotional overreactivity) are episodic phenomena

5.  1 st line therapy: MPH (methylphenidate)  Altenative drugs:  Amphetamine  Atomoxetine (ATX) in case of non-response to stimulant medication or high abuse potential  Limited knowledge of MPH effect to adult ADHD  Reimherr et al. (2007) :  positive response of MPH  a short 2x4-week not achieve robustness of the treatment over time

6.  Objective:  to access the medium- to long-term effects of extended release MPH on emotional symptom and other psychopathology frequently seen in ADHD patients  Subjects:  Outpatients with ADHD aged > 18 years, fulfill DSM-IV criteria for ADHD  Design:  MPH-ER (50% immediate release, 50% extended release)

7.  1 st five weeks:  Flexible dose schedule (10mg/day – 60mg/day)  Lower daily dose if :  Intolerable adverse event  Higher dose not increase improvement  Interval between two doses : 6-8 hours  After 5 weeks:  Min. maintenance dose : 20mg/day

8.  General assessments:  Medical history  Physical examination  Vital parameters, etc…  EEG, ECG, complete blood count  Emotional symptoms assessments:  EMS (Emotional Dysregulation Scale) :  10 items : 0-2 score per item, max score = 20  ELS (Emotional Lability Scale) :  6 items : 0-3 score per item, max score = 18  SCL-90-R (Symptom Checklist 90-Revised)

9.  ITT (intend-to-treat) population:  total:  363 - 4 (bad data quality/non-compliance)  = 359 patients  MPH ER: 241 patients  placebo: 118 individuals  Drop-out: 110 subjects (lower rate in MPH ER)  MPH ER : 13% adverse effect  Placebo : 25% lack of efficacy  PP (per protocol) population : 249 (183/66)

10.  Overall effect sizes of investigation, 0.37 by comparison study by Reimherr et al. (2007), 0.70  Use of low dose (0.55mg/kg/day) in comparison to Reimherr et al. (0.7mg/kg/day)  Concern of long term safety and tolerability of MPH  To find out whether low doses of MPH ER lead to positive response  Conclusion: differences of effect sizes is a consequence of low dose regimen

11.  Improvement of emotional psychopathology (affective lability, temper dyscontrol, and emotional overreactivity) with MPH treatment  Hypothesis : Emotional symptoms are part of ADHD psychopathology rather than comorbid condition  Robust decline of problems with self- concept and of obsessive-compulsive disorder  MPH treatment reduces classical ADHD psychopathology causing also decline of their coping strategy

12.  No improvement of anxiety and depression with MPH treatment  Anxiety and depression are only comorbid to ADHD, not part of ADHD emotional psychopathology

13.  Treatment with low doses of MPH-ER in adult patient with ADHD over a period of nearly 6 months leads to a small to medium but robust improvement of emotional symptoms.

14.  The World Journal of Biological Psychiatry, 2010; 11: 709-718  Michael Rosler, Wolfgang Retz, Roland Fischer, Claudia Ose, Barbara Alm, Jurgen Deckert, Alexandra Philipsen, Sabine Herpertz & Richard Ammer