Como eu trato TDAH? Luis Augusto Rohde Sao Paulo April, 2011
ADHD OUTPATIENT PROGRAM
Homepage manager and General Secretary: Clarissa Paim
Research assistants: Breno Matte, Henrique Ludwig, Renata Gonçalves, Gregory Zeni
School Program: Dra. Silvia Martins Reference manager: Dr. Carlos Maia (data set manager)
Nutritionist: Márcia Menegassi
Child Neurology: Lygia Ohlweiler, Rudimar Riesgo Psychiatry: Paulo Abreu, Eugênio Grevet, Carlos Salgado, Aline Fischer, Felpe Picon, Tatiana Laufer, Rafael Karam, Eduardo Vitola, Marcelo Victor, Nyvia Souza, Christian Kieling, Thiago Pianca Child and Adolescent Psychiatry: Cristian Zeni, Guilherme Polanczyk, Claudia Szobot, Marcelo Schmitz, Maria Elisa Graeff, Silvia Martins, Silza Tramontina, Carla Ketzer, Rodrigo Chazan, Carlos Maia Psychology: Luciana Anselmi, Flávia Lima, Cristina Souza Neuroimage: Neivo Júnior Genetics: Mara Hutz, Claiton Bau, Tatiana Roman, Julia Genro, Ana Paula Guimarães, Angélica Oliveira, Elisa Maggi, Evelise Polina, Verônica Contini Neuropsychology: Heloisa Kaefer, Katiane Kalil, Márcia Knjinik, Natalia Soncini Psychopedagogy: Beatriz Dorneles, Sonia Moojen, Adriana Costa, Luciana Corso CBT: Paulo Knapp, Lisiane Lyzkowski
Disclosure: Luis A Rohde, MD* Source
Consultant
Novartis JanssenCilag
X
Lilly
Speaker’s Bureau
Educational Grant**
Research Contract***
X
X
X
X
X
X
X
X
X
X
Advisory Board
Stock Equity
Abbott
X
Shire
X
Bristol
X
X
* Last 5 years ** Unrestricted Educational Grant for the ADHD outpatient Program and/or For the Pediatric Bipolar Disorder program *** Independent investigator trial- Unrestricted Research Grant
Como eu trato TDAH? Outline: Comparative efficacy & effectiveness data Doses The treatment along the day: individualizing treatment Costs
ADHD Treatment Includes a combined approach: Psychopharmacological interventions Psychosocial Interventions: a) with the family b) with the child /adolescents c) with the school • Psycho-pedagogical interventions
Psychosocial Interventions • Some level of evidence suggests the role for Behavior Parent training with school intervention for acute treatment in children
NICE - Overall conclusions for parent training in ADHD The results of the economic analysis indicate that: • Group-based parent training programmes (or CBT for children of school age) are likely to be cost-effective for children with ADHD, if the mode of delivery of such programmes does not affect their clinical effectiveness. • Individual parent training is unlikely to be a cost-effective option
Neurofeedback in ADHD - meta-analysis
Arns et al 2009
Choosing the first medication • Clearly the main choice is between stimulants and non-stimulants – Choice needs to be made on an individual basis and will depend on a range of factors including; • • • • • • • •
Strength of effect Adverse events Duration of effect Speed of response Comorbidity Abuse potential Patient and parental preference Impact in functional outcomes
Individualizing ADHD treatment
Algoritmo de Tratamento do TDAH Estágio 0
Avaliação Diagnóstica e Consulta Familiar Objetivando Alternativas de Tratamento Sem Medicação Tratamentos Alternativos
Estágios podem ser pulados dependendo do quadro clínico
Estágio 1
AMP = Anfetamina DEX = Dextroanfetamine MSA = Sais Mistos de Anfetamina TCA = Antidepressivo Tricíclico
1ª ESCOLHA
Metilfenidato ou Anfetamina Resposta Resposta Parcial Resposta Parcial ou Sem Resposta
Estágio 2
(se MAS ou DEX usados no estágio 1) Estimulante não usado no Estágio 1
Estágio A (opcional)
Resposta
Formulação de AMP não usada no Estágio 1
Continuação
Resposta Parcial ou Sem Resposta Resposta
Resposta Parcial Resposta Parcial ou Sem Resposta
Estágio 3
(se MAS ou DEX usados no estágio 2)
Atomoxetina
Estágio 2A Resposta
(opcional)
Formulação de AMP não usada no Estágio 2
Continuação
Resposta Parcial ou Sem Resposta
Pliszka et al. JAACAP 2006; 45:642-57.
Response to Methylphenidate: Double-blind Randomized Clinical Trial **
* P=.02 **P=.003
*
Szobot et al., (2004). J Att Disorders.
Faraone, 2010
Effect Sizes na Psiquiatria
Effect Size Neurolépticos Atípicos (esquizo)
0,25
ISRSs para Depressão
0,50
Medicação para TDAH Não- Estimulantes (como grupo) Estimulantes de Longa Ação*
0,62 0,95
* Faraone SV. Using a meta-analysis to draw conclusions about ADHD medication effects. American Psychiatric Association; May 21, 2003; San Francisco, Calif.
Treatment needs to target not only the core symptoms but also comorbid and coexisting disorders, other psychosocial adversities and functional impairments
Using the WHO multi-axial classificatory ICD-10 system as a routine tool can help to focus the mind on this
Comorbidity
Coghill, Rohde, Banashewski, 2008
ADHD and Anxiety • Methylphenidate – MTA data suggests that stimulants are effective at reducing ADHD symptoms in those with comorbid anxiety but strongly recommends concurrent psychological therapy – This is supported by other trial data
March, et al 2000, J.Abnorm.Child Psychol., vol. 28, no. 6, pp. 527-541.
ADHD and Anxiety ADHD RS
PARS
Geller et al 2007, J.Am.Acad.Child Adolesc.Psychiatry, vol. 46, no. 9, pp. 1119-1127.
Bloch et ., 2009
NO EFFECT ON DRUG USE!
Thurstone et al., 2010
ADHD and SUD
Doses of the main medications Methylphenidate: 1 mg/kg/day Lisdexanfetamine: 30 – 70 mg/day Atomoxetine: 1.2 – 1.4 mg/kg/day
ADHD treatment Pharmacological Interventions • Need of effectiveness across the day = ADHD is not a disorder that affects only the school life, mainly in adolescents and adults and in ADHD-C.
速 Ritalina
LA vs.
速 Concerta
MPH concentration (ng/mL)
10 8 6 4 2 0 0
4
8
12 Time (h)
Markowitz J, et al. Clin Pharmacokinet (2003) 42(4) 1-9
16
20
24
Concentração Previsível e Proporcional à Dose Sem “picos” e “vales” Concentraçao Média de d-anfetamina (ng/mL) *Crianças de 6 a 12 anos de idade
Farmacocinética Linear
Venvanse 70 mg/d Venvanse 50 mg/d
Venvanse 30 mg/d
n=18*
Tempo (h) TEMPO DE AÇÃO
Boellner SW et al. Clin Ther 2010;32:252-64
Atomoxetine Treatment Provides Continued Efficacy Into the Evening Evening Behavioral Improvements With Once-Daily Atomoxetine (Ages 6–12) Dosing
Mean Change from Baseline
Conners Global Index Parent (CGIP)-Evening Score
Atomoxetine Dosed AM Atomoxetine Dosed PM Placebo Dosed AM & PM
0 -1 -2 -3 -4
*
-5
*
*
* P < .05 vs Placebo ** P < .01 vs Placebo *** P < .001 vs Placebo
-6
**
-7
1
*
Weeks
3
*** 6
Overall LS Mean Comparison (N = 288) AM vs PLA, P < .001 PM vs PLA, P = .002 AM vs PM, P = .838
Block et al. Clin Pediatr 2009
Company Confidential Copyright© 2009 Eli Lilly and Company
Atomoxetine Treatment Provides Continued Efficacy the Next Morning Morning Behavioral Improvements With Once-Daily Atomoxetine (Ages 6–12) Dosing
Mean Change from Baseline
Conners Global Index Parent (CGIP) – Morning Score
Atomoxetine Dosed AM Atomoxetine Dosed PM Placebo Dosed AM & PM
0
-1 -2
-3 * P < .05 vs Placebo
-4 -5
*
*
-6
** ** *
-7 0
2
3
4
5
6
7
** P < .01 vs Placebo
** *
8
9
10
11
* 12
* 13
14
Days Overall LS Mean Comparison (N = 288) AM vs PLA, P = .023 PM vs PLA, P = .024 AM vs PM, P = .998
Block et al. Clin Pediatr 2009
Company Confidential Copyright© 2009 Eli Lilly and Company
NIMH Mood Chart
Wake up
AM Ready Getting Lessons for to School school
Lunch
PM Lessons
Back home
Early evening
Late Evening
Going to bed
Wake up
AM Ready Getting Lessons for to School school
Lunch
PM Lessons
Back home
Early evening
Late Evening
Going to bed
Low ADHD severity + more medication treatment at baseline
Individualizing ADHD Treatment ď&#x192;źClinical evidence-based tips: ď&#x201A;§ Treat up to no more room for improvement or presence of adverse events
Meta-analyses assessing combined treatment for children with ADHD
Majewicz-Hefley & Carlson, 2007
Relevance of treating parental ADHD
Rafael et al., 2002
QUESTIONS