Transcript Adult ADHD - Psykiatrien i Syddanmark

Course Adult ADHD
including DIVA 2.0
Odense, November 28, 2014
Dr. J.J. Sandra Kooij, MD PhD
Psychiatrist, head Expertise Centre Adult ADHD
PsyQ, psycho-medical programs
The Hague, the Netherlands
Conflicts of interest
Sandra Kooij MD PhD
• Since 2012: none
• Before 2012:
– 2 unrestricted research grants from Shire and
Janssen
– Speakers bureau of Janssen, Shire and Eli
Lilly
Subjects
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Neurobiology, prevalence & gender
Assessment of ADHD, including comorbidity
DIVA 2.0 & DSM-5
Treatment
ADHD in older people
The lifespan ADHD clinic
Neurobiology of ADHD
• Highly heritable (80% of variance explained by
genetic factors)
• Neurobiological disorder:
– brain 5% smaller and less active
– 8 kandidate genes, esp. dopaminergic (DRD2,4,5,
DAT1)
– ADHD as an inhibition deficit (no brakes) based on
dopamine deficiency
– Methylphenidate: dopamine agonist; acts as inhibitor
of associations, moodswings, restlessness and
impulsivity
Thapar 1999; Faraone 2005; Castellanos 2002; Bush 2006
Kessler 2006; Kooij 2005
ADHD symptom scores in twin studies:
highly heritable
Boomsma 2003
Martin 2002
Kuntsi 2001
Coolidge 2000
Thapar 2000
Willcutt 2000
Hudziak 2000
Nadder 1998
Levy 1997
Sherman 1997
Silberg 1996
Gjone 1996
Thapar 1995
Schmitz 1995
Stevenson 1992
Edelbrock 1992
Gillis 1992
Goodman 1989
Matheny 1980
Willerman 1973
0
0.2
0.4
Heritability
0.6
0.8
1
Other biological,
non-hereditary factors
During pregnancy:
• High bloodpressure
• Smoking
• Alcoholabuse
• Bleeding/infections
Associated with premature birth and low birthweight
During delivery:
• Hypoxia (2%)
Developmental trajectories
of brainvolumes
(Castellanos et al., JAMA,2002)
Anterior Cingulate (Cognitive Division)
Fails to Activate in ADHD
MGH-NMR Center & Harvard- MIT CITP
Bush et al., Biol. Psychiatry, 1999
Normal Controls
y = +21 mm
1 x 10-2
1 x 10-3
ADHD
y = +21 mm
1 x 10-2
1 x 10-3
The brain in ADHD
compared to NCs:
Smaller,
Hypoactive
&
Impaired
functioning
ADHD IS NOT OUTGROWN …
… in boys only?
ADHD children grow up
• ADHD in adults is a relatively new diagnosis
• Professional recognition is increasing
• But ADHD in adults has not yet been integrated in
professional education
• Children with ADHD may stay as long as possible with
pediatrician or GP, or are lost to follow up …(until age
38!)
• Adults: aware of their condition and actively looking for
help (internet)
• Patient organisations for adults are emerging worldwide
Prevalence of ADHD
through the lifespan
Children:
USA
% persisting ADHD
4 - 8%
50 - 60%
Adults:
USA
10 countries (mean)
4 - 5%
3.4%
Older people:
Sweden
Netherlands
3.3%
2.8 - 4.2%
Faraone 2003; Kessler 2006; Murphy & Barkley, 1996; Kooij 2005;
Fayyad 2007; Guldberg 2013; Michielsen 2012
ADHD and gender:
Men more often ADHD?
Children
M:F
Adults
M:F
Clinical studies
2-9x
1-2x
General
population
studies
2-3x
1 - 1.5x
Taylor 2004; Nice guidelines 2008; Kessler 2006;
Fayyad 2007; Kooij 2005
Gender differences
children and adults
Childhood
M>>F
Adulthood
M=F
Underdiagnosis in girl
Prevalence (%)
Girls have more ADD
100
90
80
70
60
50
40
30
20
10
0
Combined
Hyperactive/ impulsive
Inattentive
Girls with ADHD
(n=140)
Boys with ADHD
(n=140)
Biederman 1994, 2004
Girls and women 2x more
often ADHD inattentive type
• But majority has still ADHD combined type
• Women have to organise themselves, family,
household, childrens’ agenda’s and their job
• Being a women with ADHD is ‘a job from hell’,
always late, forgetting things …
• Chaos and tiredness their daily bread
• Low selfesteem and uncertainty about
capabilities the result
Causes of underdiagnosis of
ADHD in girls
Referral bias
ADD subtype
Internalising
comorbidity
(depression, anxiety,
premenstrual dysphoric disorder)
Assessment is comprehensive
• Lifetime ADHD symptoms and impairment (DIVA
2.0)
• Collateral information parent/spouse on ADHD
• Comorbidity: anx/depr/bipolar/sud/sleep
personality/autism/physical/
• Biography
• DSM-IV classification & treatment proposal
including order of treatment
Adult ADHD is highly comorbid
with circadian based disorders
75% has comorbidity (mean 3 disorders):
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Depression (60% SAD)
Anxiety
Substance Use Disorders
Personality Disorders
Eating Disorders (BN)
Binge eating
Obesity
Sleepproblems, DSPS pattern
25-50%
25%
20-45%
6-25%
9%
86%
30%
75%
Kooij 2001 NTG;145(31):1498-501; Kooij 2004, Psychol Med;34(6):97382, Kooij 2012, book Adult ADHD; van Veen 2010, Biol Psychiatry 67(11):
1091-6; Biederman 1993, AJP;150(12):1792-8; Kessler 2006, AJP;163(4)
:716-23; Pagoto 2009, Obesity;17(3):539-44. Davis 2009, J Psychiatr
Res;43(7):687-96. Kooij & Bijlenga, 2013
Clinical picture of ADHD
Lifetime symptoms of Attention-Deficit/Hyperactivity Disorder:
• Inattention: distracted, chaotic, forgetful, late, difficulty making
decisions, organising and planning, no sense of time, procrastination
• Hyperactive: (inner) restlessness, tense, talkative, busy; coping by:
excessive sporting/alcohol abuse/avoiding meetings
• Impulsive: acting before thinking, impatient, difficulty awaiting turn,
jobhopping, binge eating, sensation seeking
In addition in 90% of adults, lifetime:
• Moodswings (5x/day) and Anger outbursts
APA 1994; Kooij 2001, 2010; Conners 1996
Decrease of hyperactivity
in adults
Hyperactivity is adjusted, compensated for, or experienced as more
‘inner restlessness’:
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Avoiding meetings where you have to sit stil
Excessive sporting
Hectic job full of change
Cannabis / alcohol / tranquillisers against restlessness
Talkativeness, inner restlessness
The decrease in marked outward visible hyperactivity has presumably
been the reason why we mistakenly have thought that ADHD was
outgrown
Inattention most invalidating
symptom in adults
Adults need more attention than children:
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Procrastination
Chaos
Difficulty organising
Being late
Difficulty reading and remembering
Forgetting things or appointments
And yet using no watch or agenda!
Impairment in adult ADHD
In clinical as well as epidemiological samples compared to
controls:
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Learning problems (60%)
Less graduated
Lower education
Lower income
Less employed, more sickness leave
More job changes (longest job 5 yrs)
More often arrested, divorced and more social problems
More driving accidents, teenage pregnancies, suicide attempts
Higher (mental) health care costs
Biederman 2006; Kooij 2001, 2005, 2010; Barkley 2002; Manor 2010
Aid for Differential Diagnosis
• Overlapping symptoms with other
disorders …
• Unique symptoms of every disorder …
• Age of onset
• Course
• Heritability
• Treatment response
Ultrashort screening
of ADHD in adults
1. Are you usually restless?
2. Are you usually easily distracted or chaotic?
3. Do you usually do things before thinking?
If 1 of 3 answers = yes:
4. Did you have this symptom all your life?
If yes, further diagnostic
assessment of ADHD
Kooij 2010
Diagnostic Assessment of
ADHD in adults,
using DIVA 2.0
Development of DIVA 2.0
• The DIVA was developed in 2007 because there
is a need for a structured diagnostic instrument
in the field, that is easily available at low costs,
in many different languages, for research and
clinical assessment purposes.
What does DIVA 2.0 look for?
• The DIVA investigates the DSM-IV criteria of ADHD in
childhood and adulthood, as well as impairment in five
areas of functioning in both life periods.
• In order to facilitate understanding of the criteria in daily
life in both childhood and adulthood, every DSM-IV
criterion is accompanied by several examples that can
be probed.
• The same is true for the five areas of impairment:
education, work, social relationships, social
activities/leisure time, partner/family relationships and
self-esteem.
DIVA 2.0
Diagnostic
Interview for
Adult ADHD
Translation in 17 languages
All DIVAs are online free of
charge at: www.divacenter.eu
ALSO: DIVA 2.0 App
DIVA 2.0
• DIVA 2.0 has been developed to facilitate appropriate
and careful diagnostic assessment of ADHD in adults
• This semi-structured diagnostic instrument still needs
interpretation by a (trained) clinician
• DIVA 2.0 should therefore not be used by patients for
selfreport
Set-up of DIVA 2.0
DSM-IV Criterion A
Part 1) The 9 criteria for Attention Deficit (A1)
Part 2) The 9 criteria for Hyperactivity-Impulsivity (A2)
DSM-IV Criteria B, C and D
Part 3) The Age of Onset and Impairment accounted
for by the ADHD symptoms
Summary form
Score form
Order of questioning
Part 1 and 2
• Always first read the full DSM-IV criterion aloud,
ask if it is recognised in adulthood, and if yes to
give (an) example(s)
• The frequency of behaviour has to be often
• ‘Often’ is not operationalised, but refers to a
symptom being more severe and/or frequent
compared to an age and IQ matched group, or
to be closely linked to impairment
• Tick the examples mentioned
Order of questioning II
• If no examples are given, read the examples that belong
to the criterion and tick those that apply
• Start always with the adult symptom (> 6 months),
continue with the childhood presentation of the same
symptom (between 5-12 yrs)
• It is not necessary to have many examples per criterion,
also one convincing example may be enough for the
investigator to be able to decide about the absence or
presence of the criterion
Order of questionning III
• If spouse and/or parent/sibs are present, ask them after
the patient about the same symptom in resp. adulthood
and childhood
• In case of disagreement, the patient usually is the best
informant in clinical settings
• The more outward visible hyperactive behaviour is i.e.
better remembered than inattention by family members
• Collateral information serves as additional information
about severity, chronicity and impairment
• The investigator weighs all information and decides per
criterion whether it applies
Kooij ea, 2008
No collateral information
• The patient can be the sole informant to make the
diagnosis
• Collateral information serves only to get a more
complete picture, but may as well induce doubt in case
of disagreement
• Disagreement about the symptoms is common in ADHD
families…
• School reports may be helpful if the behaviour is
described, but cannot be used to reject the diagnosis if
no remark was made
• Former reports of diagnostic assessments may be useful
regarding descriptions of the same symptoms earlier in
time
Part 3: Criterion B
Criterion B: Age of onset
• Have you always had these symptoms of attention deficit
and/or hyperactivity/impulsivity?
• ❑ Yes (a number of symptoms were present prior to the
7th year of age)
• ❑ No
• If no is answered above, starting as from …. year of
age.
Part 3: Criterion C and D
Criterion C: Clinical significant impairment of which
many examples are given in 5 specified areas in
adulthood as well as childhood:
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Work/ education
Relationship/ family
Social contacts
Freetime/ hobby
Self-confidence/ self-image
Conclude if there is clinical significant impairment in 2 or
more areas
Summary form
• Count the total number of criteria met for
inattention (A) and hyperactivity/impulsivity
(HI), in both adulthood and childhood
Score form
Answer the questions on the Score form on:
1.
2.
3.
4.
5.
6.
Sufficient number of symptoms in adulthood (≥4) and
childhood (≥6)*
A lifetime pattern of symptoms and limitations (rather
than a strict age of onset!)
Symptoms and impairment manifest in 2 or more areas
No better explanation of the symptoms by other
psychiatric disorders
Level of support for the diagnosis by collateral
information
Diagnosis and subtype***
DIVA 2.0 App
in App store & Google Play store
• The DIVA 2.0 (Diagnostic Interview for ADHD in
adults) is now available as DIVA 2.0 App in both the
App store as at Google Play, for Iphone, Android and
Ipad!
• The DIVA 2.0 App contains the Diagnostic Interview for
ADHD in adults; the DIVA 2.0 App adds the total number
of DSM-IV criteria for ADHD in both child- and
adulthood, for careful diagnostic assessment of
ADHD. Data will not be stored, but sent via email, both
as text and as SPSS file.
www.divacenter.eu
Website www.divacenter.eu
All DIVAs are published online for free, to facilitate carefull
diagnostic assessment of adult ADHD worldwide
Content divacenter.eu:
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Text ‘DIVA do´s and don´ts’
English instruction video will be developed
Development of DIVA 2.0
DIVA Board
Ongoing translations
Validation studies: first in Spanish
Publications on DIVA
Contact button/information about ADHD in all languages
DIVA Foundation
• The DIVA foundation is the responsible legal
body taking charge of the quality, coordination
and distribution of the translations of DIVA 2.0
• The DIVA Foundation is a non-profit
organization that is independent from
pharmaceutical industry. Every representative of
a language pays an entrance fee for the set up
of the DIVA Foundation and website
• Commercial companies and industry pay
royalties for use of DIVA 2.0
Board DIVA Foundation, 2010
Website www.divacenter.eu
All DIVAs are published online for free
Content www.divacenter.eu:
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•
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Text ‘DIVA do´s and don´ts’
Development of DIVA 2.0
DIVA Board
Ongoing translations
Validation studies
Publications on DIVA
Contact button/information about ADHD in all languages
Validation study
• Validation studies of DIVA 2.0 are
necessary
• The first is performed in Spanish, because
they have a formal validated and
translated CAADID in Spanish to compare
with DIVA 2.0
DSM-5 changes in ADHD
Subtypes = now
Presentation types
Cutoff adolescents & adults 5/9
Age of onset
< 12 years
ADHD + ASS
Severity
NEURODEVELOP
MENTAL
DISORDERS
More examples
of behaviour
Impairment in ≥ 2 situations, but
more situations given
Training DIVA 2.0
yourself
• You are now a certified
DIVA 2.0 trainer!
• To train those who want
to use DIVA 2.0 in your language
• These slides can be used for trainings and can
be send to you all (please write your email
address)
• More help will be available from the divacenter
website
Future of DIVA 2.0
• DSM-5 was published in 2013
• DIVA-5 will be developed in 2014
www.dsm5.org; www.divacenter.eu
New diagnostic tests?
• EEG test distinquishes subtypes of ADHD
• CPT tests, Qb-test for executive functioning and
hyperactivity measures
• Voxel based MRIs
Although FDA acknowledges these methods as
‘diagnostic aids’, they are still not capable to
replace the clinical diagnosis of ADHD.
Treatment of ADHD and
concurrent disorders
1.
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5.
6.
7.
8.
Psycho- education
Discontinue alcohol/drugs
Medication for ADHD and concurrent disorders
Light Therapy for late sleep and winter
depression
Coaching
Cognitive Behaviour Therapy
Relationship therapy
Support or Advocacy Groups
Safren 2005, Weiss 2003; Kooij 2012
Available medications for ADHD
Proven effective in controlled studies:
Stimulants:
• Methylphenidate (Ritalin, Equasym, Medikinet, Concerta)®: only
licensed for kids
• Dextro-amphetamine
Non-stimulants:
• Atomoxetine (Strattera)®: licensed for kids and adults (in NLs)
• Bupropion (Wellbutrin XR)
• Modiodal (Modafinil)
Place of medication in treatment
• Medication is very effective and comes first after psychoeducation
• ADHD patients have a short attention span
• After 3 months they quit treatment if medication is not
taken or ineffective
• Coaching without medication is less effective due to less
attentiveness, irritability, forgetting appointments and
tasks, and no show
Order of treatment in
comorbid ADHD
• First treat most severe disorder, usually
depression, anxiety, bipolar disorder, SUDs;
then add stimulant for ADHD
• In case of personality disorder: first treat
ADHD
Methylphenidate (Mph)
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Best studied (> 250 RCTs)
50 years of clinical experience
Response: 70% children, 50-70% adults
Effect size .9
Better executive functioning
Safe, little side effects
Effective 20 min. after ingestion
Not addictive when used orally (but short acting can be when injected or
snored)
• Inhibits reuptake of DA / NA
• Short acting: too difficult to use due to frequent dosing need and low
compliance; risk of abuse
• Long acting best advice
Faraone 2003, Volkow ea 2002, Pietrzak 2006
Compliance in adults with ADHD?
Using shortacting Mph
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ADHD patiënts: chaotic and forgetful
Need to dose 6-8x/day ON TIME
Forget tablets, timer, batteries, water bottle and ...
No one is able to do this properly for a longer time
Efficacy low due to bad compliance
Medication wearing off generates rebound several times a
day, ´roller coaster´ in stead of stability
• Patiënts stop short acting Mph: ‘medication is worse than
disorder´
Kooij 2005
Long Acting Mph in adults
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More stable effect during the day
Less rebound
Less chance of abuse (gel or small particles hard to snore or inject)
Safer in traffic
Dose Concerta between 36-108 mg/day
Usually after wearing off Concerta, second dose needed at 3 pm (2
x 8 hr duration, total of 16 hrs coverage)
• In case of later wearing off: 2nd dose mph of intermediate duration
(5-6 hrs) at 5 pm
• Combinations of Concerta and Equasym/Medikinet
• Still waiting for stimulant with 16 hour efficacy to better serve adults
…
Duration of effect and dosing frequency
of the methylphenidates
• Ritalin:
• Equasym and Medikinet:
• Concerta:
2 - 4 hrs
5 - 8 hrs
8 - 12 hrs
(6 - 8 x/day)
(1 - 2 x/day)
(1 - 2 x/day)
Combinations are possible:
• C 72 at 8 am and C 36 at 3 pm
• C 72 at 8 am and E or M 30 at 5 pm
• C 90 at 8 am and R 10 at 8 pm
Max. dose unknown, optimal titration based on efficacy and side effects,
under control of blood pressure, pulse and weight
Most frequent side effects
Methylphenidate
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Less appetite (weight loss 1-2 kg)
Difficulty getting asleep
Changes in bloodpressure (↑↓)
Tachycardia / palpitations (propanolol)
Rebound symptoms after wearing off (less
or not with longacting stimulants)
Rebound when
methylphenidate wears off
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Half life Mph = 2 hours
Max. plasmalevel after 1,5 - 2 hours
Wears off after 2 - 4 hours
Rebound = increase of restlessness,
impulsivity, irritability and decrease of
concentration
• Preventing rebound : timely dosing or using
longacting methylphenidate
Contra-indications and
abuse potential
Methylphenidate
• Contra-indications: pregnancy, psychosis
• Relative contra-indications: hyperthyroidy,
hypertension, epilepsy, glaucoma, tics
• Abuse potential : no indication after 40 yrs
experience with oral use in children and > 15 yrs in
adults, unless used intravenously or intranasally
• Longacting stimulants protect against abuse
Response looks like:
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‘Holiday in my head’
More quiet
Better able to inhibit talkativeness or action
Less moodswings or anger outbursts
Clearing and cleaning with less effort
Better able to remember/listen
Less time needed for tasks (reading, organising)
More efficient use of time
Living room before treatment with mph
Living room after treatment with mph
Homework before and
after mph
Non-response looks like:
• Tired, fatique, ‘zombie-feeling’
• No effect
• Only side-effects
Differentiate from patients with little
introspective skills; ask spouse to
comment
SYNAPS IN NORMAL STUDIES
dopamine
Dopamine receptors
SYNAPS IN ADHD
dopamine
dopamine receptors
SYNAPS IN ADHD WITH METHYLPHENIDATE
methylphenidate
dopamine
dopamine receptors
Update on stimulant
treatment for ADHD and the
brain
• Stimulants bring the increased density of
dopamine transporters back to a normal range
• Stimulants and atomoxetine may influence longterm brain maturation, esp. when given young
enough (during pre-puberty)
• Stimulants help catching up for developmental
delay (gray matter volume increases)
Roesner ea 2011; Andersen ea 2011; Rotherberger, 2013
Nakao ea 2011; Spencer 2013
Light therapy and ADHD
5 days – 30 min – 10.000 lux – 40 cm:
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For seasonal affective disorder: in 30%
For delayed sleep phase syndrome: in 70%
For ADHD?
For overeating?
Levitan 1999, 2002; Amons & Kooij 2006, Rybak 2006,2007
Psychological treatment
‘Coaching’: practical, supportive and directive, similar to
cognitive behaviour therapy interventions:
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time management (watch, timer, agenda, mobile phone/PDA)
organising daily life (household, children, administration)
reorientation on education or work
planning time/intimacy with spouse
getting overview over finances
addressing process of acceptance of the disorder and need for
medication
• learning social and organisational skills
Coaching and
Cognitive Behaviour Therapy
• Coaching is practical / skills oriented (planning, using watch and
agenda)
• CBT is more cognitive oriented (selfesteem, negative thinking,
impulscontrol)
• Both share: transparency, here and now, structured and goal
directed
• In ADHD patients too much homework or assignments (CBT) may
induce feelings of failure, coaching is more practical, decreasing
difficulty of tasks as needed by the patient
• The coach is more equal to the patient, in CBT the therapist is not
ADHD in older
adults
An epidemiological study by M. Michielsen,
E. Semeijn, H. Comijs, D.J.H. Deeg,
A. Beekman, J.J.S. Kooij
Michielsen 2012, 2013;
Semeijn 2013a,b
ADHD IS NOT OUTGROWN
?
Fayyad J Br J Psychiatry. 2007 May;190:402-9; Kooij JJS Psychol Med. 2005 Jun;35(6):81727; Kessler RC J Occup Environ Med. 2005 Jun;47(6):565-72.; Kessler RC Am J Psychiatry.
2006 Apr;163(4):716-23.
Old people reporting childhood
ADHD symptoms
• Swedish sample, 1599 people aged 65-80 yrs
• WURS, cutoff ≥ 36
• Prevalence of self rated childhood ADHD
symptoms 3.3%, comparable to ADHD in children
and adults
• M > F (71 % vs 29%)
• Young = older groups
Taina Guldberg- Kjär, 2009
Old people reporting childhood
ADHD symptoms II
ADHD compared to no ADHD group:
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more divorce/no relationship (34% vs 12%)
more childhood problems
more jobs (> 5)
worse current health, worse current memory
Taina Guldberg- Kjär, 2009
Case studies in older adults
• Case studies in older adults indicate
similar symptoms and impairment in old
age and similar treatment response
• Epidemiological and controlled clinical
trials lacking
- Manor I. Clin. Neuropharmacology 2011
- Biederman J. JAMA 1998
- Da Silva M.A. Journal of Attention Disorders 2008
- Parker R. JAMA 1999
- Brod M. Qual Life Res 2011
Marieke Michielsen & Evert Semeijn
Presenting their posters on ADHD in old age in Berlin,
ADHD Congress, 2011
Study on the prevalence of
ADHD in older people
• Data were used from the
Longitudinal Aging Study
Amsterdam (LASA)
• Collection started in 1992/93
• Physical, emotional, cognitive and
social functioning
• Follow-up every three years
Methods
Two - phase design: screening and diagnostic
interview
Phase 1
Screening list sample
N=1494
Low scoring group
Invited
N=94
Medium scoring group
Invited
N=93
Refused: 7
Unable: 2
High scoring group
Invited
N=84
Refused: 12
Unable: 2
Deceased : 1
Refused: 12
Deceased : 1
Phase 2
Interviewed
Phase 2
Interviewed
Phase 2
Interviewed
N=85
N=80
N=69
ADHD diagnoses
Two diagnostic categories, based on DIVA 2.0
were used:
Syndromatic ADHD, full blown DSM-IV diagnosis
- 6/9 symptoms in present time and childhood
Symptomatic ADHD, sub-clinical diagnosis
- 4/9 symptoms in present time and 6/9 childhood
Prevalence of ADHD in older people in
the general Dutch population
Age: 61-95 years: lower prevalence of ADHD in
the older old.
Women: 59%
Syndromatic ADHD
Symptomatic ADHD
%
95% Cl
%
95% Cl
2.8
0.86–4.64
4.2
2.05–6.39
Men
3.0
-0.20–6.12
4.6
0.96–8.39
Women
2.6
0.38–4.72
3.8
1.39–6.24
Total
Sex
Michielsen 2012
ADHD and anxiety/depression
in older people
• ADHD was associated with more anxiety
and depressive symptoms crosssectionally as well as longitudinally
compared to controls.
Michielsen 2013
ADHD and physical health in
older people
• ADHD in older people was associated with
chronic nonspecific lung diseases
(CNSLD), cardiovascular diseases, and
number of chronic diseases.
• ADHD was negatively associated with selfperceived health.
Semeijn 2013
ADHD and social functioning
in older people
ADHD in older people:
• was associated with being divorced or never married
• less family members in their network
• emotional loneliness
Level of ADHD symptoms was associated with more
• emotional and social loneliness
• lower income level
• NB depressive symptoms play an important role in the
association between ADHD and loneliness
Michielsen ea 2013
Conclusions
• The prevalence and comorbidity with anxiety and
depression in older people with ADHD, show similar
patterns as in younger age groups
• Regarding physical health there are indications that older
people with ADHD may have worse health outcomes
and may die younger
• Lower income, less intimate relationships, less family
relationships, more loneliness and depression in older
people with ADHD
Can ADHD be treated
in older people?
• 15 case studies: patients (m, f), age 67-81 yrs
• ADHD from childhood, diagnosis in (grand)children, who respond
favorable to medication for ADHD
• Lifespan restlessness, irritability, impulsiveness and distractedness
leading to impairment
• Succesfully treated with stimulants in old age
• Monitoring cardiovascular side effects before and during treatment
Wetzel 2008; Da Silva & Louza, 2008;
Standaert, Kok & Kooij, 2010; Manor ea, 2011
Impairment is
not
diminishing
Similar
prevalence
rates
ADHD is not
outgrown
in older people
Similar
medication
response
Needed:
RCT’s!
Needed:
Lifespan clinics!
The ADHD Lifespan Clinic
The ADHD Lifespan Clinic?
• A place where ADHD patients of all ages can be
diagnosed and treated
• A place where professionals are specialists in
ADHD and comorbidities throughout the lifespan
• A place where you can easily return to in case of
relapse or need of adjustment of treatment, and
where your lifetime patient record file is always
available
• An excellent place for longitudinal cohort and
family studies of ADHD
Current organisation of
Mental Health Care for ADHD
1. General Child Psychiatry
2. General Adult Psychiatry
3. General Psychiatry for older people
IMAGINE HAVING ADHD …
… in childhood
• Your parents will turn to a pediatrician or to child
psychiatry where you usually get help after a long time
waiting
IMAGINE HAVING ADHD …
… in adulthood
• Your GP will tell you that ADHD
does not exist in adults, and send
you to general mental health care
… where you will be diagnosed
with one or more other disorders
that are usually comorbid with
ADHD, but your ADHD is not
recognised
• This is due to lack of knowledge in professionals who have never
been educated about this highly prevalent disorder in adulthood
IMAGINE HAVING ADHD
… in old age
• Your GP now really starts
laughing when you ask for
diagnostic assessment, although
your daughter and granddaughter
were recently diagnosed with
ADHD, and successfully treated
… you really thought there was still some hope for you
as well, but you find out that innovative new knowledge is
usually very reluctantly implemented in mental health care
IMAGINE HAVING ADHD
- IN OUR TIME • The good news is that new knowledge and treatment
options are available
• The bad news is that general mental health care
services usually don’t deliver it
• When you outgrow the safe heaven of child psychiatric
care, you’ re facing a desert of ignorance and disbelief
among professionals
• When you enter adult psychiatry YOU are the one to
teach your physician and therapist about ADHD
• When you enter old age psychiatry, you will have to
repeat the same effort for the second time
Conclusion
You will have difficulty finding
expertise on your disorder
during a lifetime
Or:
Your life will be over
before new knowledge will be implemented
in general mental health care!
Results of the current age
related gaps in services
• Adolescents stop their treatment in large numbers after
age 15
• … they only return as adults in their thirties, with an
increased rate of comorbidity and a lot of damage to
education, career, relationships
• Where parents are supposed to be the reliable persons
to educate their children with ADHD, they themselves
are often impaired by the same disorder
• This leads to impaired families, and high (mental) health
care costs without the desired outcomes
Who can deliver lifespan
services to ADHD patients?
• The hands of child psychiatry are too short to continue
treatment in / after adolescence
• The last two decades, adult psychiatry, let alone general
mental health care for older people, has not taken the
challenge of implementing care for ADHD in their daily
practice
• This has not happened anywhere in the world …
• So why wait any longer?
• An organisation that does not take into account the
lifespan course of ADHD cannot do the job
• So: let’s get started!!
The Lifespan ADHD Clinic?
IT’ S ABOUT TIME!
How to set up a lifespan
ADHD clinic?
1. Start cooperation with child, adult and old age psychiatry
involved, or interested in ADHD
2. Determine similar assessment routes and treatment
algorhythms for each age group, based on their needs
3. Pay special attention to adolescents who quit treatment
around age 15
4. Build a team that works together in the same building
Set up a lifespan clinic?
Is it easy?
•
•
•
•
•
•
Eh, not really!
It takes different organisations
Different people
Different management
Different financial routes
You must really be determined and
motivated to do it!
Is it rewarding?
• Yes!
• People with ADHD like it!
• Professionals are ready for it and like it as
well
• Mental health care is not ready, but this
will not happen unless we do get started!
ADHD, circadian rhytm, sleep, mood and
season
ADHD
100%
DSPS
75%
Over
weight
SAD
BP II
30%
10%
Goikolea 2007, Psychol Med;37 (11):1595-9;
Amons 2006, J Affect Disord;91(2-3):251-5;
Lewy 2006, Proc Natl Acad Sci U S
A;103(19):7414-9;
Van Veen 2010, Biol Psychiatry 67(11):
1091-6
Bijlenga 2013, J Att Disord; 17(3):261-75
Bijlenga 2013, J Sleep Res. Aug 16 epub
Sleep questionnaire in
120 adults with ADHD
Difficulty …
•
•
•
•
•
going to bed on time:
falling asleep:
sleeping through:
getting up in the morning:
daytime sleepiness:
78%
70%
50%
70%
62%
This pattern lifetime in 60%, suggestive of
Eveningness or Delayed Sleep Phase Syndrome
Kooij, Society of Light Treatment and Biological Rhythms 2007
Chronotypes:
being a lark or an owl
•
•
•
•
•
•
•
Morningtype: gets up early, active in morning (20-25%)
Eveningtype: late to bed, active in evening (20-25%)
In between: 50%
Normal variation may differ +/- 2 hrs
More variation disallows normal participation in society
Clockgenes define chronotype and biological rhythm
Zeitgebers: light through the eyes in the morning, and
melatonin production in the brain at night synchronise us
with the light/dark cycle of the world
• Artificial light may delay melatonin production at night
(computer!)
Are most adults with ADHD
evening types?
•
•
•
•
•
•
•
•
•
Evening types are more active at night, prefer to go to bed late
They get up late as well
Evening types may be late due to a delayed onset of melatonin
If sleeping longer is not possible due to work or school obligations, a
chronic sleep dept can result
Working in evening- or nightshifts may be adaptive
Question: do adults with ADHD work more often in nightshifts?
And if so, is that a problem?
Morningness is associated with low impulsiveness / sensation seeking.
Eveningness the other way round…
Barkley 1997, J Dev Behav Pediatr,18(4):271-9. Caci 2004, Eur Psychiatry.;19(2):79-84.
Levitan 2004, Biol Psychiatry;56(9):665-9. Van Veen 2010, Biol Psychiatry 67(11): 1091-6;
Kooij 2012, book Adult ADHD
ADHD patients lack
any sense of time
Clinical experience: adults with ADHD seem to lack
any sense of time, as well as any rhythm in day/night
Their habitually being late has been regarded as part of
their inattentiveness, a planning problem, but may in fact
reflect a fundamental problem of the biological clock
Nucleus supra chiasmaticus
(NSC): the biological clock
Hypothalamic nucleus, just above the chiasma opticum
Delayed Sleep Phase Syndrome
DSPS is characterized by:
- (Very) late chronotype
- A chronic pattern of (very) late sleep and preference for
late rise
- May result in daytime sleepiness and/or insomnia
- May be compensated for by an irregular sleep pattern
- Leads to dysfunctioning due to increased inattentiveness
and/or social problems
- Main complaint is sleep onset insomnia
Sleep phase delay in ADHD
30
25
20
normal type
eveningtype
15
10
Melatonin level
5
0
Time
Biological clock
and body rhythms
Characteristics of
40 consecutive ADHD patients
Sleep Onset
Insomnia (SOI)
No SOI
N
31 (78%)
9 (22%)
Male
17 (55%)
4 (44%)
Age, mean (SD)
28.2 (7.6)
30 (11.9)
ADHD, combined type
29 (94%)
5 (56%)
ADHD, inattentive type
2 (6%)
4 (44%)
Alcohol (U/wk)
6.76
5.67
Nicotine (Sig/day)
8.16
1.11
Sleep diagnosis
ns
ns
Van Veen 2010, Biological Psychiatry;67(11):1091-6.
Dim Light Melatonin Onset (DLMO): delayed
N=40 adults with ADHD w/wo Sleep Onset Insomnia
versus healthy controls
DLMO
(hr ± sd)
ADHD
Total
SOI
no-SOI
HC
p:
ADHD
vs HC
p:
SOI
vs HC
22:57 ± 1:20
23:15 ± 1:19
22:00 ± 0:54
21:34 ± 0:45
0.000
0.000
- 78% of consecutive ADHD patients had SOI
- DLMO: 105 min later in SOI vs HC
- After DLMO, it generally takes 2 hours to fall asleep
Van Veen ea, 2010
24 hour movement patterns ADHD + SOI compared to controls (actigraphy)
Van Veen ea 2010
New study: core and skin temperature,
DLMO and activity patterns
• N=12 ADHD+DSPS (medication naïve) and 12 controls
• 5 consecutive days and nights
Results:
• More variable bedtimes in ADHD, but melatonin onset is the same
every day in both groups
• DLMO 1.5 hours later in ADHD
• Sleep duration 1 hr shorter on days before workdays in ADHD
• Second delay, between DLMO and sleep onset was ≥ 1 hr longer in
ADHD
• Melatonin, activity and temperature were all delayed to a similar
degree in ADHD
• Overall temperatures were lower in ADHD
• Colder hands in ADHD, related to sleep onset difficulties
Bijlenga, J Sleep Res, 2013 Aug 16
24 hr Activity,
Core and Skin
Temperature,
in ADHD versus
controls
Bijlenga, J Sleep Res 2013,
Aug 16
ADHD and disturbed rhythms
ADHD may not only be associated with circadian, but also
with cyclical and seasonal disturbances, leading to
problems with impulsiveness, eating, sleeping and mood:
• Impulsivity/novelty seeking has been associated with eveningness
• Lack of sleep rhythm may lead to lack of rhythm in eating and activity
patterns as well
• Evening types, or those with a delayed sleep phase may prefer irregular
work or work in night-shifts, thereby increasing the sleep phase delay,
as well as obesity
• ADHD has a higher percentage of Seasonal Affective Disorder (SAD) or
winter depression, and possibly also of Premenstrual Dysphoric
Disorder than normal
Barkley 1997, J Dev Behav Pediatr,18(4):271-9;
Amons 2006, J Affect Disord;91(2-3):251-5
Caci 2004, Eur Psychiatry.;19(2):79-84.
Levitan 2004, Biol Psychiatry;56(9):665-9
Antunes 2010, Nutr Res Rev.(1):155-68.
ADHD & seasonal mood changes
• Adult ADHD co-occurs with lifetime
depressive disorder in 55%
• Most of them (60%) have
Seasonal Affective Disorder (SAD) or winterdepression
• Open trial of Light therapy effective for SAD and ADHD, as well as
for Delayed Sleep Phase
• SAD has a circadian phase delay in 70%
• Are SAD and ADHD related via circadian disturbances?
• Clockgenes associated with ADHD
Levitan 1999, Compr. Psychiatry, 40(4), 261-7;
Johansson 2003, Neuropsychopharmacol;28(4):734-9;
Amons 2006, J Affect Disord;91(2-3):251-5;
Rybak 2007, Compr Psychiatry;48(6):562-71;
Lewy 2006, Proc Natl Acad Sci U S A;103(19):7414-9;
Kissling 2008, Am J Med Genet B, Neuropsychiatr Genet;147(3):333-8.
Circadian disturbance, ADHD
and health
• ADHD is associated with chronic DSPS
• ADHD patients often work in night shifts or are active at night
• May be gene-environment interaction: circadian preference based
on (clock)genes and dopaminergic pathways
• But: chronic work (>30 yrs) in night shifts is associated with higher
risk of (breast)cancer
• Melatonin acts as a circadian anti-cancer signal at night
• Among others (light at night), chronic low melatonin levels may
protect less well against development of cancer
is ADHD a high riskgroup for cancer?
Schernhammer 2001, J Natl Cancer Inst;93(20):1563-8;
Schernhammer 2005, Eur J Cancer;41(13):2023-32; Hansen 2001, J
Natl Cancer Inst;93(20):1513-5; Blask 2005, Endocrine;27(2):179-88.
Moser 2006, Conf Proc IEEE Eng Med Biol Soc;1:424-8; Verkasalo
2005, Cancer Res;65(20):9595-600.
2.00
Relative risk of breastcancer
First degree relatives
Flight attendants
Hormone Replacement Therapy
Shiftwork
1.50
Alcohol > 45 g/day
BMI> 30
First birth > 35
Current use of contraceptives
Nulliparous
1.00
Physical activity
1 full time pregnancy
Increased
risk
Decreased
risk
First birth <20
Breastfeeding
0.50
>7 children
Moser 2006, Conf Proc IEEE Eng Med Biol Soc;1:424-8
Does cancer risk cluster in ADHD?
Several lifestyle risk factors may cluster in
ADHD individuals:
•
•
•
•
•
Night shift work
High BMI
Alcohol/drug abuse
Smoking
Low melatonin levels?
Short sleep and cancer risk
• Shift work is considered carcinogenic in the long term
(IARC 2007)
• Sleep loss by shiftwork is associated with higher
incidence of breast- and prostate cancer
• Short sleep
short exposure to and/or low levels of
melatonin
• Melatonin has anti-oxidative properties and protects
against cancer growth
• Animal research shows inhibiting effects of melatonin on
cancer growth and increased survival
• In humans, first studies with melatonin in cancer patients
ongoing
Schernhammer 2004, 2006; Parent ea 2012;
Sigurdardottir ea 2012; Anisimov ea 2012
Cancer risk and exposure
to light@night
• Use of artificial light at night stops melatonin production
through the eyes, feedback to pineal gland
• The light coming from TV, PC or Ipad also suppresses
melatonin production and delays natural sleep onset
easily by hours
• Light is the natural antidote to melatonin and wakes us
up every day …
• Timing of light may be crucial for health in general
• Women with total visual blindness have less cancer than
sighted women
Flynn-Evans ea, 2009
ASESA study
• To explore the sleep/wake patterns,
psychiatric and somatic comorbidity, BMI
and eating patterns in adults with ADHD
(n=202) compared to the general
population (n=189)
Bijlenga ea, 2013
General characteristics
ADHD, n=202
Controls, n=198
p
Women
47 %
65 %
<.001
Age: mean
34.9
33.0
.121
BMI: mean
24.8
23.2
<.001
BMI ≥ 30 (obese)
17 %
4%
<.001
Unemployed
27 %
6%
<.001
Smokes
52 %
18 %
<.001
>14 U alcohol p/wk
17 %
7%
.016
Self-reported Morbidities
(showing only significant differences)
% ADHD, n=202
% Controls, n=198
p
Depressed mood
18
6
<.001
Stress/ burnout/ fatigue
5
1
<.001
Pulmonary problems
31
16
<.001
Cardiovascular problems
43
18
<.001
Gastro-intestinal problems
33
19
.001
Metabolic problems
12
6
.042
Immune system problems
7
3
.049
Skeletal problems
50
36
.005
Sleep characteristics
Age ≤ 30 yrs
Age > 30 yrs
ADHD
n=83
Controls
n=106
P
ADHD
n=119
Controls
n=83
p
Bed time work days: mean
23:45
23:10
.002
23:33
23:00
.001
Bed time free days: mean
01:02
0:13
<.001
0:20
23:41
.002
Sleep length work days: mean
7:25
7:55
.029
7:01
7:42
<.001
Sleep-onset latency
work days: mean
0:39
0:22
.002
0:34
0:12
<.001
Indication of DSPS: 26% in ADHD vs. 2% in controls (p<.001)
Summary
• More morbidities, complaints, and unhealthy
lifestyle in ADHD
• More (extreme) evening chronotype in ADHD
• More sleep problems in ADHD: shorter sleep,
longer sleep-onset latency, later mid-sleep,
more variable bed times
• DSPS relates to SAD and to health issues
• This is also apparent within the control group
• Shorter sleep is related to a higher BMI
Next step: biomarkers in
ADHD and DSPS
PHASE study: Phase shift in ADHD of sleep
and appetite:
• 50 adults with ADHD and DSPS
• 3 wk treatment: Mel, Plac, Mel+LT
• Measurement at baseline, after 3 wks Tx
and after 3 wks washout: DLMO, cortisol,
leptin/ghrelin, glucose, insuline markers,
inflammation markers, HRV
Vogel ea, in preparation
ADHD index predicts
weight and binge eating
Binge eating group
Probability
Obese group
Normal weight group
ADHD index
CAARS
Davis 2009, J Psychiatr Res;43(7):687-96
Late sleep = short sleep
late meals
Possible impact of a delayed rhythm on weight and health:
•
•
•
•
•
•
•
•
Sleeping late may lead to a short sleep duration
Short sleep duration is associated with obesity
Adults with ADHD tend to skip breakfast
Breakfast skipping is associated with obesity
ADHD patients suffer from eating problems in 80%, mostly binge eating
Their weight fluctuates 10 - 20 kg’s
ADHD is associated with increased BMI
Obesity is associated with diabetes, cardiovascular disease and cancer
Kooij 2012, book Adult ADHD;
Dubois 2009, Public Health Nutr;12(1):19-28;
Boere 2008, NTG;152(6):324-30;
Davis 2009, J Psychiatr Res;43(7):687-96;
Mota 2008, Ann.Hum.Biology;35(1)1-10;
Copinschi 2000, Novartis Found Symp;227:143-57
Spiegel 2005, J Appl Physiol;99(5):2008-19
Sleep loss causes
loss of control over appetite
Leptin (satiety hormone) and ghrelin (hunger hormone):
• Reducing sleep duration by 2 hours already lowers levels of
leptin, the satiety ("fullness") signal
• Sleep restriction study (n=12): leptin ↓ by 18% and ghrelin ↑
by 28%, leading to increased appetite and feelings of
hunger
• 13 epidemiologic studies in adults and 8 in children: sleep
loss is associated with increased BMI
• Sleep loss is a novel risk factor for insulin resistance and
type 2 diabetes
Lauderdale 2006, Am J Epidemiol;164(1):5-16; Lauderdale 2009, Am J
Epidemiol;170(7):805-13. Spiegel 2005, J Appl Physiol;99(5):2008-19;
Copinschi 2005, Essent Psychopharmacol;6(6):341-7; Shea 2005, J Clin
Endocrinol Metab;90(5):2537-44;
Sleep duration USA
10
9
8
7
6
5
sleep duration
4
3
2
1
0
1960
2002
2004
2006
As sleep time fell in USA, average weights rose
Whether and how sleep time and weight are connected is still unclear
Kripke 2002; Keith 2006; Lauderdale 2006
Treatment of ADHD
in obese patients
•
•
•
•
•
N=242 patiënts with severe therapy resistent obesity, ADHD in 32%!
Comorbidity: depression, sleep apnea, binge eating
75% of the ADHD group got stimulant treatment
Stimulants: effective for ADHD, and inhibit appetite
Weight loss: 15 kg in stimulant treated group, while others increased
3 kg during treatment for obesity
• After follow up at 1.5 yrs, in which medication was continued, the
results remained
• Patiënts: less restlessness, anxiety and tiredness, & needed less
food to compensate for these feelings. Binge eating disappeared,
better contact with feeling of hunger and satiety.
• Better able to plan and comply to the treatment for obesity.
Pagoto ea 2010; Albayrak ea 2011; Levy ea 2009
Proposed treatment / prevention
of obesity in ADHD
To reset the clock and increase sleep duration:
• Psycho education on the meaning of time, the light/dark cycle for sleep,
appetite, metabolic entrainment, mood and health
• Sleep hygiene (early to bed and early to rise …)
• No light@night, shower before going to bed, bedsocks
• Melatonin in evening*
• Light in morning
To reduce binge eating and weight gain:
• Treatment of comorbidity (depr/anx)
• Treatment of ADHD with stimulant
• Exercise, diet
*Melatonin has not been reviewed or approved by the FDA for the
treatment of sleep disorders. Kooij, book Adult ADHD 2012
Melatonin treatment
• To fall sleep: 3 mg at 22:00 in order to sleep at
23:00
• To reset the clock: 0.1 mg - 0.5 mg between
16:00 and 19:00, in steps of 1.5 hour/wk from
the normal sleep time to the desired bedtime
• Circadin 2 mg for those who wake up
nevertheless at 03:00 am
• No light exposure of tablets of melatonin!
Lewy 2005, 2006, continued; Kooij 2012 Book Adult ADHD
Desired sleep time – 8 uur =
time of intake of 0.5 mg melatonine
Desired sleep time
01:00 am
Time of intake
Melatonin
5 pm
00:30 am
4.30 pm
11-12 pm
4 pm
Do not use melatonine < 4 pm or > 12 pm!
Light therapy in the morning
• Especially in winter more sleep phase delay
• More difficult to get up on time
• Inducing strong early morning light artificially, usually
does work as sunlight in summer
• Melatonin is reduced through closed eyelids by light,
which is our natural wake up call
• Light box of 500 W, or Light therapy device 10.000 lux
and timer 30 min before wake up time
• Wake Up Light uses only 75 W and does not wake all
patients with delayed sleep phase
• Warning: 500 W light becomes hot and contains UVA+B
Rybak ea 2006
Adult ADHD
Diagnostic Assessment and Treatment
Including DIVA 2.0
JJS Kooij, 3rd edition
2012
www.springer.com
Search for ‘Adult ADHD’
10 year Anniversary of (the 28) PsyQ Programs Adult
ADHD in the Netherlands, October 2013
• For patient driven & patient oriented research
• First: online questionnaire inventarising most
needed subjects from both patients and
researchers
• Preferred research subjects (n=219): ADHD &
Mood, Health, ASS, and Sleep
• Patients determine which research will be
funded
• ADHDFund = Patient empowerment!
www.adhdfund.com
Support Taina’s Guldberg’s
research at ADHDFund!
www.adhdfund.com
First study on ADHD in older
people with cognitive decline!
Online: December 2014 – February 2015!