Palestra sobre Transtorno de Déficit de Atenção e Hiperatividade

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