Non-stimulant Behavioral MedsA Staff Coffee Potpourri

Edward J. Coll, LTC(P), MC

Chief, Developmental Pediatrics

The Usual Suspects

Methylphenidate

Dextroamphetamine

Racemic amphetamine mixture (Adderal)

Pemoline (Cylert)

Methylphenidate

Short, intermediate, long-acting options– rule of 3’s

Ritalin = Brand Name– Focus-in on The Simpsons

Sprinkles: Metadate CD Hard capsule, osmotic pump: Concerta d-threo-methylphenidate: Focalin

d-amphetamine

Short, intermediate options– rule of 3’s

Dexedrine = Brand Name– tablet, sprinkles

Sprinkles: Dexedrine spansules 1st used, but now 3rd place

– still good meds

d-amphetamine/dl-amphetamineAdderal

Intermediate, long acting

Tablet: intermediate

Sprinkles/capsule: Adderal XR

Atomoxetine

Selective norepinephrine uptake inhibitor Little effect on dopamine or serotonin

uptake Little effect on Ach, H1, alpha-2, DA

receptors Well-tolerated in adult studies

Atomoxetine…AD/HD…Randomized, Placebo-Controlled, Dose-Response...

297 children and adolescents 8-18 years old; 71 % male 70% had prior stimulant therapy Combined/Inattentive/Hyper-impulsive 63/33/2 % 37 % Oppositional-defiant disorder 1 depression, 1 anxiety disorder

Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Doses Measured

0.5 mg/kg/d div BID 1.2 mg/kg/d div BID 1.8 mg/kg/d div BID

– < highest studied doses in adults

8 week period

Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Measures: Behavioral

Parent rating only, not school Interviewer ADHD rating scale (ADHD RS) Parent ADHD rating scale (Conners’) Clinical Global Impressions of Severity Childhood Depression Rating Scale Child Health Questionnaire

Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Measures: Physiologic

Cytochrome P450 2D6 category– extensive vs– poor metabolizers (7% of US population)

#6 in placebo group, 11 in atomoxetine group

Side effects Heart rate, BP, EKG analysis, weight change

Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Conclusions

Well tolerated at all doses (1.2 = 1.8 mg/kg) Superior to placebo in most measures

– all core AD/HD measures BP, pulse changes similar to methylphenidate

studies Dose-dependent weight loss Poor metabolizers had comparable response

– small sample size–

Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

Open-label study 30 7-14 year olds; 89% with comorbid dx 0.25-1.9 mg/kg/day divided BID 11 week titration 39% reduction in ADHD interview scores 29 % reduction in CGI-ADHD-S rhinitis 33%, headache 20%, anorexia 16.7%,

dizziness 16.7%–

J of Child and Adolescent Psychopharm 2001; 11:521-265

Directions

1st Study extends to one year

Recruiting for study of ADHD + tic disorders Comparison to stimulant

– e.g. Concerta vs TID methylphenidate Best role in AD/HD comorbid management

– antidepressant properties–

Modafinil (ProVigil)

A non-stimulant stimulant Narcolepsy, daytime drowsiness in... 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/HDOpen-label study

11 5-15 years old, M:F = 9:6 started Combined/inattentive/hyper-impulsive 12/2/1 started

– 2 noncompliant with protocol– 1 hand-foot-mouth disease– 1 adverse rxn: episodic hand tremor + MS change

very mixed bag of comorbidities: PDD, TS...

J of Am Acad of Child and Adol Psychiatry 2001; 40:230-235

Modafinil in AD/HDOpen-label study

AD/HD measures– Conners’ Parent and Teacher– ADHD Rating Scale IV for Parent and Teacher– Test of Variables of Attention (TOVA)

Side effects Vital signs, weight

J of Am Acad of Child and Adol Psychiatry 2001; 40:230-235

Modafinil in AD/HDOpen-label study

Once daily dosing

Start 100 mg titrated to maximum 400 mg

Length of time avg 4.6 weeks (range 2-7 wks)

J of Am Acad of Child and Adol Psychiatry 2001; 40:230-235

Modafinil in AD/HDOpen-label study

AM dose effect into afternoon Improved Conners’ and ADHD Rating Scales Improved TOVA impulsivity scores

– but not inattention scores Delayed sleep (3), stomachache, headache,

lightheadedness, tremors, finger-biting (1)

J of Am Acad of Child and Adol Psychiatry 2001; 40:230-235

Modafinil BE AWAKE all you can be!

WRAIR

3 doses of modafinil vs 600 mg caffeine Performance testing in sleep deprivation Enhances performance and alertness No advantages over caffeine

Psychopharmacology (Berl) 2002 Jan;159(3):238-47

Modafinil BE AWAKE all you can be!

Aeromedical Research Lab., Ft. Rucker, AL Aviator alertness and performance 6 pilots, 40 hour wakeful periods compared Placebo vs 3 x 200 mg modafinil 4/6 performance measures improved, reduced

slow wave EEG, better mood, alertness side effects: vertigo, nausea, dizziness

Psychopharmacology (Berl) 2000 Jun;150(3):272-82

Asleep at the Throttle