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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
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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.