Non-stimulant Behavioral Meds A Staff Coffee Potpourri Edward J. Coll, LTC(P), MC Chief, Developmental Pediatrics

The Usual Suspects n Methylphenidate n Dextroamphetamine n Racemic amphetamine mixture (Adderal) n Pemoline (Cylert)

Methylphenidate n Short, intermediate, long-acting options – rule of 3’s n Ritalin = Brand Name – Focus-in on The Simpsons n Sprinkles: Metadate CD n Hard capsule, osmotic pump: Concerta n d-threo-methylphenidate: Focalin

d-amphetamine n Short, intermediate options – rule of 3’s n Dexedrine = Brand Name – tablet, sprinkles n Sprinkles: Dexedrine spansules n 1st used, but now 3rd place – still good meds

d-amphetamine/dl-amphetamine Adderal n Intermediate, long acting n Tablet: intermediate n Sprinkles/capsule: Adderal XR

Atomoxetine n Selective norepinephrine uptake inhibitor n Little effect on dopamine or serotonin uptake n Little effect on Ach, H1, alpha-2, DA receptors n Well-tolerated in adult studies

Atomoxetine…AD/HD…Randomized, Placebo-Controlled, Dose-Response... n 297 children and adolescents n 8-18 years old; 71 % male n 70% had prior stimulant therapy n Combined/Inattentive/Hyper-impulsive n 63/33/2 % n 37 % Oppositional-defiant disorder n 1 depression, 1 anxiety disorder Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Doses Measured n 0.5 mg/kg/d div BID n 1.2 mg/kg/d div BID n 1.8 mg/kg/d div BID – < highest studied doses in adults n 8 week period Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Measures: Behavioral n Parent rating only, not school n Interviewer ADHD rating scale (ADHD RS) n Parent ADHD rating scale (Conners’) n Clinical Global Impressions of Severity n Childhood Depression Rating Scale n Child Health Questionnaire Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Measures: Physiologic n Cytochrome P450 2D6 category – extensive vs – poor metabolizers (7% of US population) n #6 in placebo group, 11 in atomoxetine group n Side effects n Heart rate, BP, EKG analysis, weight change Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Conclusions n Well tolerated at all doses (1.2 = 1.8 mg/kg) n Superior to placebo in most measures – all core AD/HD measures n BP, pulse changes similar to methylphenidate studies n Dose-dependent weight loss n Poor metabolizers had comparable response – small sample size – Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Open-label study n year olds; 89% with comorbid dx n mg/kg/day divided BID n 11 week titration n 39% reduction in ADHD interview scores n 29 % reduction in CGI-ADHD-S n rhinitis 33%, headache 20%, anorexia 16.7%, dizziness 16.7% – J of Child and Adolescent Psychopharm 2001; 11:

Directions n 1st Study extends to one year n Recruiting for study of ADHD + tic disorders n Comparison to stimulant – e.g. Concerta vs TID methylphenidate n Best role in AD/HD comorbid management – antidepressant properties –

Modafinil (ProVigil) n A non-stimulant stimulant n Narcolepsy, daytime drowsiness in... n Mechanism ? – Alter balance of GABA and glutamate which activates the hypothalamus – Increases metabolic rate of amygdala and hippocampus – activates hypocretin(orexin)-containing neurons, (which are disrupted in narcolepsy)

Modafinil in AD/HD Open-label study n years old, M:F = 9:6 started n Combined/inattentive/hyper-impulsive n 12/2/1 started – 2 noncompliant with protocol – 1 hand-foot-mouth disease – 1 adverse rxn: episodic hand tremor + MS change n very mixed bag of comorbidities: PDD, TS... J of Am Acad of Child and Adol Psychiatry 2001; 40:

Modafinil in AD/HD Open-label study n AD/HD measures – Conners’ Parent and Teacher – ADHD Rating Scale IV for Parent and Teacher – Test of Variables of Attention (TOVA) n Side effects n Vital signs, weight J of Am Acad of Child and Adol Psychiatry 2001; 40:

Modafinil in AD/HD Open-label study n Once daily dosing n Start 100 mg titrated to maximum 400 mg n Length of time avg 4.6 weeks (range 2-7 wks) J of Am Acad of Child and Adol Psychiatry 2001; 40:

Modafinil in AD/HD Open-label study n AM dose effect into afternoon n Improved Conners’ and ADHD Rating Scales n Improved TOVA impulsivity scores – but not inattention scores n Delayed sleep (3), stomachache, headache, lightheadedness, tremors, finger-biting (1) J of Am Acad of Child and Adol Psychiatry 2001; 40:

Modafinil BE AWAKE all you can be! n WRAIR n 3 doses of modafinil vs 600 mg caffeine n Performance testing in sleep deprivation n Enhances performance and alertness n No advantages over caffeine Psychopharmacology (Berl) 2002 Jan;159(3):238-47

Modafinil BE AWAKE all you can be! n Aeromedical Research Lab., Ft. Rucker, AL n Aviator alertness and performance n 6 pilots, 40 hour wakeful periods compared n Placebo vs 3 x 200 mg modafinil n 4/6 performance measures improved, reduced slow wave EEG, better mood, alertness n side effects: vertigo, nausea, dizziness Psychopharmacology (Berl) 2000 Jun;150(3):272-82

Asleep at the Throttle