ADHD dall’infanzia all’età adulta€¦ · –High stimulus seeking behaviour: •Inherent component of ADHD (e.g. novelty seeking) •Shared genetic risk –Impaired social/academic/work

ADHD dall’infanzia all’età adulta:

evoluzione clinica e trattamento

Giulio Perugi, MD

Istituto di Scienze del Comportamento “G.De Lisio”, Pisa

Dipartimento di Medicina Clinica e Sperimentale, Sezione

di Psichiatria, Università di Pisa, Pisa

ES

Un paziente che nonostante la diagnosi e le

terapie corrette continua ad avere problemi

Descrive la sua vita come difficile e diversa

Grande disorganizzazione ed incapacità di

concludere a casa e sul lavoro

Grande difficoltà a raggiungere gli obiettivi

Bassa autostima

Sono sempre stato così

Come è il paziente adulto con ADHD

che chiede aiuto allo psichiatra?

Circa il 75% dei disturbi psichiatrici degli adulti è

preceduta da disturbi ad esordio prima dei 18 anni (50%

prima dei 15 anni).

La psicopatologia infantile è spesso diversa da quella

che ritroveremo nell’adulto (sviluppo eterotipico).

La definizione delle traiettorie evolutive dei più

importanti disturbi psichiatrici ha un importante valore

preventivo sulla salute mentale della popolazione.

Dall’infanzia all’età adulta:

la prospettiva evolutiva

• L’ADHD passa sotto la soglia clinica in 1/3 degli

adolescenti e nel 50% degli adulti.

• Non necessariamente le comorbidità seguono lo

stesso destino, per cui i disturbi “favoriti” dall’ADHD

possono seguire un percorso autonomo, sia in

adolescenza sia in età adulta.

Percorsi evolutivi dell’ADHD

I SINTOMI NUCLEARI DELL’ADHD

• Iperattività

• Impulsività

• Inattenzione/Disorganizzazione

• Disregolazione Emotiva (ciclotimia)

Sintomi aspecifici

Continuum normalità-patologia

“Comorbidità”

DSM 5: cambiamenti nei criteri

diagnostici

Inizio dei sintomi prima di 12 anni

Non più sottotipi ma “presentazioni”

Criteri più sensibili per soggetti adolescenti

o adulti

Per adolescenti > 17 anni ed adulti, sono

richiesti 5 anziché 6 sintomi.

Autismo non più criterio di esclusione

• Inattention

• Over-activity

• Impulsiveness

• Ceaseless mental activity (distracted mind)

• Mood lability / emotional dysregulation

• Low tolerance of frustration

• Low self-esteem

• Variable performance

DSM criteria (core symptoms)

Associated Symptoms

Symptoms of ADHD are non specific

1. Asherson. 1st European Network Adult ADHD Conference. London, 2011.

ADHD: TRAIETTORIA EVOLUTIVA

La fenomenica nell’età adulta cambia

rispetto a infanzia e adolescenza.Biederman et al. AJP 2000

… per l’interazione di

molteplici fattori …

• Disorganisation (“doesn’t plan ahead”)

• Forgetfulness (“misses appointments, loses things”)

• Procrastination (“starts projects but can’t complete”)

• Time management problems (“always late”)

• Premature shifting of activities (“starts something but then quickly distracted by something else”)

• Impulsive decisions (especially around spending, taking on projects, travelling, jobs or social plans)

• Criminal offences (speeding, illegal drugs)

• Unstable jobs and relationships

Clinical Presentation in Adults

1. Kooij & Francken. DIVA Foundation 2010.

• Disorganisation (“doesn’t plan ahead”)

• Forgetfulness (“misses appointments, loses things”)

• Procrastination (“starts projects but can’t complete”)

• Time management problems (“always late”)

• Premature shifting of activities (“starts something but then quickly distracted by something else”)

• Impulsive decisions (especially around spending, taking on projects, travelling, jobs or social plans)

• Criminal offences (speeding, illegal drugs)

• Unstable jobs and relationships

Clinical Presentation in Adults

1. Kooij & Francken. DIVA Foundation 2010.

Diverse tipologie di pazienti adulti

con ADHD

1. Predominanti sintomi di inattenzione e difficoltà di organizzazione

Lentezza sul piano cognitivo e pragmatico, difficolta prestazionali e di funzionamento

frequente la comorbidità con depressione e ansia

2. Impulsività marcata e iperattività ampia sovrapposizione con i disturbi dello spettro bipolare e di

personalità, spesso in comorbidità con uso di sostanze

Malingering e disturbi fittizi

Più complicati da gestire

• Anxiety:1

– Ceaseless thoughts, avoidance behaviour

• Depression:1

– Unstable mood, impatience, irritability, initial insomnia, low self-esteem

• Personality disorder:1

– Antisocial, borderline, emotionally unstable, poor social interactions, impulsive, adulthood instability trait-like quality

• Hypomania, bipolar ll disorder, cyclothymia:2

– Differentiated by grandiosity, clear focus of thoughts, episodic, reduced need for sleep, psychosis

Comorbidity and symptoms of ADHD

1. Asherson. 1st European Network Adult ADHD Conference. London, 2011.

2. Babcock and Ornstein. Postgraduate Medicine. 2009;121(3):73-82.

ADHD as a Risk Factor for Development

of Co-occurring Conditions Later in Life

Environmental and genetic risks:

(maltreatment / COMT* genotype)

Risk Model

Adult with ADHD

• Antisocial behavior• Addiction• Depression/low self-esteem• Anxiety

*Catechol-O-methyl transferase

1. Asherson. 1st European Network Adult ADHD Conference. London, 2011.

• Dyslexia (overlapping genetic risk factors)1

• Specific and general learning difficulties (overlapping genetic risk factors, inattention)1

• Pervasive developmental disorder1

• Dyspraxia1

• Tic disorders/Tourette's disorder1

• Speech problems2

• Autism spectrum disorder1

Overlapping Neurodevelopmental Disorders

1. Kooij et al. BMC Psychiatry 2010;10:67

2. Tannock et al J Abnl Child Psychol, 2000; 28(3):237–252

aPrevalence estimates of ADHD in the subsamples with the comorbid disordersbPrevalence estimates of the comorbid disorders in the subsample with ADHD

Conditional Prevalence Estimates, %(SE)1

OR (95% CI)ADHD in other

disorderaOther disorder in

ADHDb

Classes of co-occurring disorders

Mood 11 (1.2) 25 (2.6) 3.9 (3.0–5.1)

Anxiety 10 (1.0) 38 (3.1) 4.0 (3.0–5.2)

Substance use 12.5 (2.3) 11 (2.0) 4.0 (2.8–5.8)

Comorbidities in ADHD

1. Fayyad et al. Br J Psychiatry 2007;190:402–9.

• Reason for the relationship:

– High stimulus seeking behaviour:

• Inherent component of ADHD (e.g. novelty seeking)

• Shared genetic risk

– Impaired social/academic/work function:

• Secondary consequence of psychosocial

impairments

– Relief from symptoms:

• Self-treatment of symptoms (e.g. cannabis, alcohol,

cocaine)

ADHD and Substance Misuse

1. Arias et al. Addictive Behaviors 2008;33(9):1199–207.

2. Asherson. 1st European Network Adult ADHD Conference. London, 2011.

• Lifetime prevalence 9.5% (14.7% males, 5.8%

Females

• Early onset of BD (5 years before)

• Comorbid anxiety, alcohol and substance use

disorders

• Increased rates• ADHD in relatives of BD-I probands

• BD-I in relatives of ADHD probands

• Not accounted for by misdiagnosis

• Comorbidity as a distinct familial subtype ?

Prevalence: 17/96-19.1%

Early onset

Comorbidity (ICD, SUD, GAD)

Problems with antidepressants

Treatment

• Children’s Guidelines for Treatment

• Adults = ???

• Overview

– Symptom reduction/minimize

– Education

– Psychotherapy

– Pharmacological

ADHD is an heterogeneuos disorder

DSM-IV Clinical subtypes

• Inattentive

• Hyperactive/Impulsive

• Combined

Neuropsychology Models

• Executive Dysfunction

• Motivational Dysfunction

• Delay Adversion

• Response Variability

• Speed in Cognition & Arausal

DSM-IV ADHD vs

ICD-10 Hyperkinetic Dis.

Comorbidities

• Disruptive behaviours (ODD, CD, Antis P)

• Neurodevelopmental (i.e.dyslexia, ASD)

• Tics & Tourette Syndrome

• Severe Mood Disregulation (bipolar ?)

• Anxiety and Depression

• Bipolar Disorder

• Drug and alcohol abuse

A TRIPLE PATHWAY HYPOTHESIS

CORTICO-DORSAL

STRIATAL LOOP

DISTURBANCE

INHIBITORY

DEFICITS

EXECUTIVE

DEFICITS

CORTICO-VENTRAL

STRIATAL LOOP

DISTURBANCE

IMPAIRED SIGNAL

DELAYED REWARD

DELAY AVERSION

ADHD subtypes

CORTICO-

CEREBELLAR LOOP

DISTURBANCE

TEMPORO-SENSORY-

MOTOR INTEGRATION

DEFICITS

MOTOR

ASYNCHRONY

Psychosocial Intervention

– CBT

– Self-Mgmt Skills Training

– Environmental Restructuring

– Psycho-education

– Individual Psychotherapy

– Family Therapy

– Marital/Couple Therapy

– Vocational Counseling

– ADHD Coaching

DRUGS

– Well established in children with ADHD

• Stimulants (first line drugs)

• Atomoxetine (Strattera)

• Children (70-80% respond)

• Adults (25-78% respond) (30% don’t!!!!)

– Atomoxetine (Strattera)

– Methylphenidate (Ritalin)

– Amphetamine compounds (Adderall)

– Dextroamphetamine (Dexedrine)

Stimulant administration • Metilphenidate

– Short-acting,low dose = titrate up

• Ritalin = 3 – 4 hours

– Move towards longer acting stimulants

• Equasym = 6-12 hours

• Medikinet = 8-16 hours

Stimulants: Pros & Cons• Pros:

– Highly effective

– Long history of use

• Cons:

– Limited duration of action

– Side effects [e.g., Nausea, headache, insomnia,

decreased appetite, tics (up to 65% w/MPH),

anxiety, HTN/tachycardia, psychosis]

– Contraindications [HTN, symptomatic

cardiovascular disease, glaucoma,

hyperthyroidism, tics/Tourette’s (relative), drug

abuse (relative), psychosis (relative)]

Stimulants, Abuse,

and ADHD Patients

• CNS stimulants are rarely abused by children and

adolescents with ADHD

• Used properly, they decrease the likelihood of

later substance abuse in these patients

• In adults long-term stimulants may be associated

with misuse

• In adults with comorbid substance abuse,

malingering and stimulant misuse is frequent

Anti-depressants

– Atomoxetine (Strattera)**

– Tri-cyclics (Desipramine-Norpramin)

– MAOI (tranilcipromine)

– Bupropion (Wellbutrin)-atypical

– Venlafaxine (Effexor)-atypical

**= Strattera, indicated for ADHD

• Bipolar-ADHD

• Severity

• Substance abuse

• Malingering-diversion

• Stimulants very effective in ADHD

• Mood instability

• Atomoxetine

• Substance abuse

• Malingering-diversion

TEST IMPLEMENTATION

Saliva Sample

DNA Analysis & Interpretation

User-friendly Pharmacogenetic Report

Stable at room temperature

CLINICAL CASE 2

• Demographics: Male 19 y/o

• Condition: ADHD, DSA, Long-lasting mood instability, impulsivity, severe functional disability

• Treatment:

1. Fluoxetine: Poor tolerability

2. Citalopram, quetiapine, olanzapine: Very poor tolerability

3. Valproate: no effect

Conclusioni

• L’ADHD nell’adulto è poco diagnosticato

– Scarsa familiarità con I disturbi del neurosviluppo

– Elevata comorbidità con disturbi dell’umore, d’ansia, da uso di

sostanze, di personalità.

• ADHD può essere considerato un fattore di rischio per lo

sviluppo di altri disturbi mentali

• La co-occorrenza di ADHD, Disturbo Bipolare e uso di

sostanze sembra delineare un fenotipo specifico

• Richiede un trattamento specifico anche nell’adulto

• Atomoxetina approvata nell’adulto

• Gli stimolanti richiedono procedura off-label

Domande e Commenti ?

“La mente umana deve

costruire le forme,

indipendentemente, prima

di poterle trovare nelle

cose.”

Albert Eisnstein, 1927

CORSO PRATICO DI FARMACOTERAPIA

PSICHIATRICAAdulto, età evolutiva, anziano, doppia diagnosi

ROMA, 7-10 OTTOBRE e 16-19 DICEMBRE 2015

OLY HOTEL - Via Santuario Regina degli Apostoli, 36

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[email protected]

Faculty

Albert U.Brugnoli R.De Bartolomeis A.Di Sciascio G. Girardi P.Koukopoulos A.Maina G.Maremmani I.

Masi G.Mazzarini L.Mecocci P.Medda P.Perugi G.Pompili M.Sani G.Tondo L.Toni C.Vampini C.Zuddas A.