Institute 1:Timothy E. Wilens Institute 1: Timothy E. Wilens
ADHD Pharmacological Straegies in Treatment Refractory ADHD
Substance Use Disorders Advanced Psychopharmacologic Interventions
for Adolescent Substance Use Disorders Bipolar Disorder
Pharmacologic Strategies and Tactics for Treating Bipolar Disorder
Juvenile Depression Juvenile Depression Anxiety Disorders
Pharmacological Treatment of Anxiety Disorders Tics and Tourettes
Disorder Tics and Tourettes Disorder Autism Psychopharmacology of
Autism and Related Disorders
Refractory ADHD: Prominent Executive Function Deficits Use of
Norepi agent Atomoxetine, TCA, Bupropion (alone or combined with
stimulant) Nicotinic/cholinergic agents Indirect: Donepezil,
Galantamine Ineffective Direct: Nicotinic agents/patch -
Effective
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Atomoxetine Uses Uncomplicated ADHD Refractory ADHD Comorbid
ADHD Anxiety or depressive disorders Tic disorders Disruptive
disorders Substance use disorders
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Atomoxetine Dosing (Wilens Method): Dosing (Wilens Method):
Start at 0.5 mg/kg/day for 2 weeks, then increase to 1.2 mg/kg/d
After 6 weeks if partial response, increase to 1.4 mg/kg/d (FDA
approval) 1.8 mg/kg/d (studied) Reduce dose to 0.5 mg/kg/d if using
known inhibitors of p448 (e.g. paroxetine, fluoxetine,
ketoconazole)
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Atomoxetine Adverse effects: Adverse effects: - Somnolence,
insomnia, nausea, headache, appetite suppression, GI
upset/dyspepsia, BP/pulse (adults), sexual dysfunction (adults)
Drug interactions: Drug interactions: - Other p448 inhibitors can
inhibit Atomoxetine catabolism (paroxetine, fluoxetine) - No drug
interactions with stimulants
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MGH Study: Atomoxetine + OROS MPH in ADHD (Wilens et al.
unpublished data) Improved ADHD RS (p=0.028) Improved CGI-Severity
of ADHD (p=0.009) 85% of combined group considered much/very much
improved Significant effect on executive functioning High rates of
side effects
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Bipolar Disorder Pharmacologic Strategies and Tactics for
Treating Bipolar Disorder
Newer Antiepileptic Drug (AEDs): Gabapentin Mimics GABA, low
S/E Adults: 2 controlled studies did not demonstrate efficacy in
acute mania Cases of Disinhibition in children Dosing Start 150-300
mg Target range 900-2400 mg/d
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Newer Antiepileptic Drug (AEDs): Lamotrigine Adults: 2
controlled studies demonstrated efficacy for bipolar depression Not
FDA-indicated in children age < 16 years Concern: serious
rashes, Steven-Johnsons syndrome, serum sickness Small open label
study in 20 adolescents with bipolar depression: 84% response (by
CGI- C), 63% response (by CDRS-R)
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Newer Antiepileptic Drug (AEDs): Topiramate Blocks
voltage-gated sodium channels Half-life: 21 hours (with inducers
12-15 hours) Controlled adolescent trial was negative. 2 adult BPD
controlled studies were also negative. Start dose at 25 mg bid;
increase to 200 mg bid
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Newer Antiepileptic Drug (AEDs): Oxcarbazepine 10-keto analogue
of carbamazepine Lower adverse effects than CBZ Results of
child/adolescent trial pending Dosing Start 150-300 mg/d Effective
range 900-1800 mg/d
Treatment of Adolescent Depression Study (TADS) Approximate 400
adolescents with MDD 11 sites, NIMH Randomized to 12 weeks:
Fluoxetine up to 40 mg CBT Fluoxetine plus CBT Placebo TADS: JAMA
2004;292:807-20
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TADS: CGI-I response at the end of 12-weeks of Px
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Effect Size for CGI-I (ITT)
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Suicidal Behavior General population: 17% of teens think about
suicide in given year 12% of girls and 5% of boys make a suicide
attempt Complete suicide: Girls = 2/100,000 Boys = 12/100,000
35-50% of depressed teens make a suicide attempt
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Pharmacological Treatment of Anxiety Disorders
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Pediatric OCD Treatment Study (POTS) Multicenter NIMH-funded
study of 112 youths (7-16 yrs) with OCD Comparison of 12-wk
CBT+Sertraline, CBT alone, Sertraline alone and placebo JAMA,
2004
School-Based CBT for Anxious Children Comparison of group CBT
for children, group CBT + parent training, and no-treatment control
Both active CBT interventions were more effective than control in
decrease anxiety level. Adding parent training to child CBT
resulted in additional benefits.
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Psychopharmacology of Autism and Related Disorders
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Risperidone Best studied Efficacious in controlling aggression,
irritability, stereotypy, and hyperactivity Not efficacious in
social impairment and communication deficit
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Other atypical antipsychotic trials in autism Clozapine:
efficacious in 3 case reports Olanzapine: efficacious in 2
open-label trials Quetiapine: mixed efficacy in 4 retrospective
studies Ziprasidone: efficacious in 1 case series Aripiprazole:
efficacious in 1 case series
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Atomoxetine in PDDs with ADHD symptoms Prospective open-label
study in 16 drug-free children with PDDs + significant ADHD
symptoms Dosing: 0.5 mg/kg/d x 1 wk, then 0.8 mg/kg/d x 1 wk, then
1.2 mg/kg/d Dose increased to 1.4 mg/kg/d at week 4 for
nonresponders Mean dose = 1.2 +/- 0.3 mg/kg/d
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Atomoxetine in PDDs with ADHD symptoms 12/16 (75%) much or very
much improved on the CGI 2/16 (13%) much worse due to irritability
Conclusions Encouraging results Possible alternative to stimulants
and clonidine Placebo-controlled studies needed
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Core Symptom: Social Withdrawal Donepezil (Aricept) better than
placebo in crossover study of 43 PDDS children Ongoing single site
trials of donepezil and galantamine (Reminyl) D-cycloserine (NMDA
partial agonist) reduced ABC social withdrawal in small pilot study
(N=10)