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
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)
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
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
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)
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
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)
ITT (intend-to-treat) population: total: (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)
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
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
No improvement of anxiety and depression with MPH treatment Anxiety and depression are only comorbid to ADHD, not part of ADHD emotional psychopathology
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.
The World Journal of Biological Psychiatry, 2010; 11: Michael Rosler, Wolfgang Retz, Roland Fischer, Claudia Ose, Barbara Alm, Jurgen Deckert, Alexandra Philipsen, Sabine Herpertz & Richard Ammer