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Non-stimulant Behavioral MedsA Staff Coffee Potpourri
Edward J. Coll, LTC(P), MC
Chief, Developmental Pediatrics
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The Usual Suspects
Methylphenidate
Dextroamphetamine
Racemic amphetamine mixture (Adderal)
Pemoline (Cylert)
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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
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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
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d-amphetamine/dl-amphetamineAdderal
Intermediate, long acting
Tablet: intermediate
Sprinkles/capsule: Adderal XR
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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
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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
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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
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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
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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
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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
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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
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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–
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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)
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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
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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
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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
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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
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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
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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
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Asleep at the Throttle