Presentation on theme: "Ritalin ® & AD/HD just calming the troublemaker ??? Dr.med.Sven Schellberg Global Communications & Brand Manager Psychiatry NOVARTIS Pharma AG, Basel,"— Presentation transcript:
Ritalin ® & AD/HD just calming the troublemaker ??? Dr.med.Sven Schellberg Global Communications & Brand Manager Psychiatry NOVARTIS Pharma AG, Basel, Switzerland
Dont worry, potentially a new Ritalin ® customer
What do these gentlemen have in common ?
ICD-10 versus DSM IV Inattentiveness Impulsivity Disturbed activity (Hyperactivity) hyperactive impulsive Type inattentive Type hyperkinetic Syndrome F90 combined Type
ADHD School Occupational status Social/financial status Peer relationships Marital status Traffic accidents Drug abuse Delinquency
Statistics % of pupils (age 6 – 16) show symptoms of AD/HD Hyperactivity is more common in boys in 70 % of the patients, symtomatology calms in adolescence 30 % keep symptoms which need therapy in adulthood
AD/HD in adolescence / adulthood
Attention, evaluation of situations, learning and activity are functions which are located in dopaminergic areas of the brain In animal experiments a depression of dopaminergic function leds to hyperactivity, aggression and worsening of learning procedures
Etiology Krause et al.
Etiology Bush et al.
Etiology Family and Interactions Education Environmental Effects Food
Diagnosis History and anamnesis including interviews with patient, parents, teachers Symptomatology (differing criterias between DSM IV (AAP) and ICD-10) Rating Scales (CRS, CBCL etc.) Exclusion of other medical disorders (e.g. epilepsy, brain damage, schizophrenia, hyperthyreosis) physical examination including EEG, lab, intelligence testing
Treatment of AD/HD always has to combine educational, psychotherapeutical and psychopharmacological methods
Stimulants The use of stimulants started in the 1930s when their stimulative effects on the dopamingergic system and their psychotropic effects were discovered First Amphetamine and Metamphetamine were used First descriptions of an use of Methylphenidate in MCD in the 1960s Detailed descriptions in the 1980s by Wender et al.
Mode of action First a paradox way of action was assumed when Methylphenidate, a stimulant, improved attention and hyperactivity of the children AD/HD was explained as a dopamine deficit syndrome, which is treated by stimulants by an increase in neurotransmitter release This theory was not able to explain the missing tolerance effect of the drug and its efficacy in non hyperactive only inattentive patients
Mode of action Krause et al.
AD/HD Because of time one example of efficacy only
Substance Abuse relative risk
Product backgrounder and competitors Ritalin ® LA
Methylphenidat IR vs. SR
Facts and Problems Onset of action after 20 – 40 minutes Duration of action 2-4 hours Repeated dosing – often over school-time - mandatory Acute tolerance requires peaked doses with raising plasma levels over the day and drug free interval at night Stable plasma levels show poor clinical efficacy, sharp increase in plasma levels in the morning required
Ritalin ® LA - Objectives Fast onset of action in the morning, with a high morning dose Double peak pharmacokinetic with raising plasma levels over the day Duration of action about 8 – 10 h to cover schoolday, but not to interfer with sleep at night Easy to swallow, no food interaction Easy switch from standard medication Individualized dosing
Ritalin ® LA - SODAS
Ritalin ® LA 20 mg (n=19) Markowitz J, et al. Clin Pharmacokinet. In press. Ritalin ® LA
Concerta ® - OROS Concerta ® is a trademark of Janssen Cilag, / J&J
Ritalin ® LA 20 mg (n=19) Time (h) Concerta ® 18 mg (n=19) MPH concentration (ng/mL) Markowitz J, et al. Clin Pharmacokinet (2003) 42(4) 1-9 Ritalin ® LA vs. Concerta ®
Important differences Concerta ® Dose strenghts 18, (27), 36, (54) mg Initial dose 22 % Sustained dose 78 % Duration of action up to 12 h Capsule must not be opened Ritalin ® LA Dose strenghts 20, 30, 40 mg Initial dose 50 % Sustained dose 50 % Duration of action up to 8 h Capsule may be opened and sprinkled on soft food Concerta ® is a trademark of Janssen Cilag, / J&J
How to switch ? Switching can be done from day to day Switching sometimes needs new dose adjustment Always remind initial 50 % of dose (10 mg, 15 mg, 20 mg) Starting with too high doses may lead to initial side effects and bad compliance ! Previous methylphenidate doseRecommended Ritalin Uno dose 10 mg methylphenidate b.i.d or 20 mg methylphenidate SR 20 mg qd 15 mg methylphenidate b.i.d30 mg qd 20 mg methylphenidate b.i.d or 40 mg of methylphenidate SR 40 mg qd
Pharmacodynamics Or what does this mean in daily practice ?
School Day Efficacy of Ritalin ® LA vs. Concerta ® Randomized, rater blind, placebo controlled clinical trial 36 children, 6-12 years, 29 boys, 7 girls All stabilized on 20 mg MPH/die ahead of trial 4 way crossover design Study medication on days 7, 14, 21, 28, standard medication in-between Swanson, Kotkin, Alger M-Flynn, Pelham (SKAMP) Attention/Deportment Scale Age/intelligence-appropriate, 400-question, 10-minute written math test
*P=0.015 for Ritalin ® LA 20 mg vs Concerta ® 18 mg. P=0.043 for Ritalin ® LA 20 mg vs Concerta ® 36 mg. P<0.001 vs all active treatment groups. Change from Baseline (Predose) 0-4 Hours N=36 WorseningImprovement Ritalin ® LA 20 mg Concerta ® 18 mg Concerta ® 36 mg * Placebo Ritalin ® LA vs. Concerta ® SKAMP Attention over first 4 hours
Change from Baseline (Predose) 0-8 Hours N=36 * WorseningImprovement Ritalin ® LA 20 mg Concerta ® 18 mg Concerta ® 36 mg Placebo *P=0.074 for Ritalin ® LA 20 mg vs Concerta ® 18 mg. P=0.208 for Ritalin ® LA 20 mg vs Concerta ® 36 mg. P<0.001 vs all active treatment groups. Ritalin ® LA vs. Concerta ® SKAMP Attention over schoolday
Time (h) Mean change from predose in SKAMP-combined N=36 Placebo Concerta ® 36 mg Concerta ® 18 mg Ritalin ® LA 20 mg *P<0.05 for Ritalin ® LA 20 mg vs Concerta ® 36 mg. P<0.05 for Ritalin ® LA 20 mg vs Concerta ® 18 mg. * * * * 0 Ritalin ® LA vs. Concerta ® SKAMP Combined
Strattera ® (Atomoxetine, Eli Lilly) Atomoxetine is a norepinephrine-reuptake inhibitor, orginally developed as antidepressant (Pharmacia) Atomoxetine has no dopaminergic activity Atomoxetine is the first non-stimulant approved for treatment of AD/HD Atomoxetine is the first pharmacologic treatment, approved for the use of adult AD/HD Onset of action as with other antidepressants is delayed (4 – 6 weeks at minimum)
Strattera ® (Atomoxetine, Eli Lilly) Efficacy of Atomoxetine seems to be lower than that of stimulants Common side effects are nervousness, sleeplesness, loss of appetite, decreased body weight, sexual dysfunction, especially in boys In US Atomoxetine gained 15 % market share in AD/HD market within 6 months after launch Approval and launch in EU has been delayed several times – expected currently for H2/2004