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Diagnostic Assessment, Treatment, and Lifespan Clinic for ADHD

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1 Diagnostic Assessment, Treatment, and Lifespan Clinic for ADHD
Brescia– June 2014 Dr. J.J. Sandra Kooij, MD PhD Psychiatrist, head Department Adult ADHD and Expertise Centre Adult ADHD PsyQ, psycho-medical programs The Hague, the Netherlands

2 Topics Clinical picture Gender and age Prevalence
Diagnostic assessment, DIVA 2.0 Differential diagnosis Circadian rhythm disturbances in ADHD and relationship with mood and health Treatment Lifespan Clinic for ADHD

3 Adult ADHD Diagnostic Assessment and Treatment
Including DIVA 2.0 JJS Kooij, 3rd edition 2012 Search for ‘Adult ADHD’

4 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; Conners 1996

5 Decrease of hyperactivity
Hyperactivity is adjusted, compensated for, or experienced as more ‘inner restlessness’: 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

6 Inattention most invalidating symptom in adults
Adults need more attention than children: Procrastination Chaos Difficulty organising Being late Difficulty reading and remembering Forgetting things or appointments Using no watch or agenda!

7 ADHD in DSM-IV Attention-deficit/hyperactivity disorder
18 criteria: 9 attention problems (A) and 9 hyperactive/impulsive criteria (HI) Diagnosis in childhood from 6/9 of one or both domains 3 subtypes: ADHD, inattentive type (also ADD) (10-15%) ADHD, hyperactive/impulsive type (3%) ADHD, combined type (85%)

8 Impairment in ≥ 2 situations, but
DSM-5 changes in ADHD Cutoff adoles- cents & adults 5/9 NEURO- DEVELOP MENTAL DISORDERS Subtypes = now Presentation types Age of onset < 12 years ADHD + ASS More examples of behaviour Severity Impairment in ≥ 2 situations, but more situations given

9 Impairment in adult ADHD
In clinical as well as epidemiological samples compared to NCs: 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; Barkley 2002; Manor, 2010

10 ADHD and gender: Men more often ADHD?
Children M : F Adults Clinical studies 2 - 9 x 1 - 2 x General population studies 2 - 3 x x Taylor 2004; Nice guidelines 2008; Kessler 2006; Fayyad 2007; Kooij 2005

11 Gender differences children and adults
Childhood M>>F Adulthood M=F Underdiagnosis in girls

12 Girls have more ADD Biederman 1994, 2004

13 Causes of underdiagnosis of ADHD in girls

14 Complaints girls and women with AD(H)D

15 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

16 Room with a view?

17 Is ADHD like Chronic Fatigue Syndrome (CFS)
Is ADHD like Chronic Fatigue Syndrome (CFS)? Inattentive girls referred for being´tired´? Clinical studies: boys more often ADHD Epidemiological research: girls similar percentage ADHD as boys ADHD in girls is less well known, and their behaviour less disruptive than in boys … Boys have more often: ADHD, combined type More severe hyperactivity Externalising comorbidity (oppositional defiant or aggressive behaviour) Being disruptive helps to get help…. Biederman ea, 1994; 2002, 2004; 2005

18 Girls are not disruptive …
Inattention takes continuous mental effort, leading to exhaustion … … but may be chronically tired!

19 ADHD and CFS need further study
Screening for ADHD in Burnout or CFS group Methylphenidate treatment in subgroup with diagnosis of ADHD may ameliorate tiredness and inattention Physical complaints in ADHD need further study (RSI, burnout, neck- and backpains, obesity, chronic tiredness, chronic sleep-problems)


21 ADHD in older adults An epidemiological study by M. Michielsen,
E. Semeijn, H. Comijs, D.J.H. Deeg, A. Beekman, J.J.S. Kooij

22 ADHD IS NOT OUTGROWN ? Fayyad J Br J Psychiatry May;190:402-9; Kooij JJS Psychol Med Jun;35(6):817-27; Kessler RC J Occup Environ Med Jun;47(6): ; Kessler RC Am J Psychiatry Apr;163(4):

23 Prevalence of ADHD in children and adults
USA % Adults USA % 10 countries (mean) 3.4% US incl diagnostiek NL alleen zelfrapportage, onderrapportage…? APA 2000; Faraone 2003; Kessler 2006; Murphy & Barkley, 1996; Kooij 2005; Fayyad 2007


25 Persistence of ADHD depends on definition of remission
Biederman, 2000

26 Treatment % per country in adults with ADHD
Medical treatment Mental Any Treatment for ADHD Belgium 10.4 13.8 21.5 Italy 10.6 4.4 11.9 NL 18.6 18.8 23.8 1.9 USA 27.9 28.6 49.7 13.2 Fayyad 2007

27 Old people reporting childhood ADHD symptoms
Swedish sample, 1599 people aged 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

28 Old people reporting childhood ADHD symptoms II
ADHD compared to no ADHD group: more divorce/no relationship (34% vs 12%) more childhood problems more jobs (> 5) worse current health, worse current memory Taina Guldberg- Kjär, 2009

29 Dutch epidemiological study ADHD in adults
N=1800, age 18-75 Self reported DSM-IV ADHD-Rating Scale Prevalence % (cutoff 6, resp. 4 current symptoms) Hyperactivity: small, significant age dependant decline, but not for Inattention and Impulsivity Group yrs = 17.7% of the study population Prevalence in this oldest group % (cutoff 6, resp. 4 current symptoms) Kooij ea 2005

30 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

31 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

32 Marieke Michielsen & Evert Semeijn
Presenting their posters in Berlin, ADHD Congress, 2011

33 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 In the 90’s random sample, stratified by age sex, was drawn three areas. Collection started in 1992/93 Study changes in physical emotional cognitive and social functioning in late life. 2008/ respondents particiapted To Limit diagnostic interview, two phase design was used. 33

34 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 High scoring group Invited N=84 Refused: 7 Unable: 2 Refused: 12 Deceased : 1 Refused: 12 Unable: 2 Deceased : 1 In the 90’s random sample, stratified by age sex, was drawn three areas. Collection started in 1992/93 Study changes in physical emotional cognitive and social functioning in late life. 2008/ respondents particiapted To Limit diagnostic interview, two phase design was used. First screening list, based on score, diagnostic interview (aged 61-95) For the screening, we used a screening list developed by Barkley, and his colleagues, for screening adults. The list has 9 items which can be answered with yes and no. If participants responded with a positive answer to any of these, an additional item about chronicity was asked. It has been validated among young adults, but not among older adults. For diagnosing ADHD, we used The Diagnostic Interview for Adult ADHD. This is a Dutch interview based on the DSM-IV criteria for diagnosing ADHD among adults, and the interview and it is widely used in dutch clinical practices and now also abroad. The interview consists of two parts: one for assessing the presence of all 18 DSM-IV TR criteria in childhood and at present; the other to assess impairment in functioning in daily life due to the ADHD symptoms  Now I will go in with the first question/study on prevalence after this study I will go on with the validation study of the screeninglist Phase 2 Interviewed N=85 Phase 2 Interviewed N=80 Phase 2 Interviewed N=69 34

35 Screening list by Barkley
1 Is often easily distracted by extraneous stimuli or irrelevant thoughts 2 Often makes decisions impulsively 3 Often has difficulty stopping his or her activities or behaviour when he or she should do so 4 Often starts a project or task without reading or listening to directions carefully 5 Often shows poor follow-through on promises or commitments he or she may make to others 6 Often has trouble doing things in their proper order or sequence 7 Often more likely to drive a motor vehicle much faster than others (excessive speeding) Alternative: Often has difficulty engaging in leisure activities or doing fun things quietly 8 Often has difficulty sustaining attention in tasks or play activities 9 Often has difficulty organizing tasks and activities  For the screening, we used a screening list developed by Barkley, and his colleagues, for screening adults. Tthey developed the questionnaire from 91 questions. The list has 9 items which can be answered with yes and no. If participants responded with a positive answer to any of these, an additional item about chronicity was asked. It has been validated among young adults, but not among older adults. Barkley RA, Murphy KR, Fischer M. ADHD in adults: What the science says. The Guilford Press; 2007. 35

36 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 Two different cut-off scores Originally for children Clinical observation show that adults have different symptoms Consequently, in the last few years, a number of researchers have questioned the validity of this diagnosis in adults. New suggestions for the adjustment of the adult ADHD diagnosis have been proposed, such as reduction in the cut-off for diagnosis using DSM-IV. First is fullblown ADHD or syndromatic Second symptomatic We calculated the prevalence estimates and weighted it back to the general dutch population, 36

37 Prevalence of ADHD in older people in the general Dutch population
Age: years: lower prevalence of ADHD in the older old Women: 59% Syndromatic ADHD Symptomatic ADHD % 95% Cl Total 2.8 0.86–4.64 4.2 2.05–6.39 Sex 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 The prevalence of ADHD is 2.8%,of sub clinical ADHD is 4.2%. Among men the percentage is slightly higher Michielsen 2012 37

38 ADHD and anxiety/depression in older people
ADHD was associated with more anxiety and depressive symptoms cross-sectionally as well as longitudinally compared to controls. Michielsen 2013

39 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 self-perceived health. Semeijn 2013

40 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, submitted

41 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

42 Impairment is not diminishing Similar prevalence rates ADHD is not outgrown in older people Similar medication response Lifespan clinics needed! RCT’s needed

43 Can ADHD be treated in older people?
15 case studies: patients (m, f), age 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

44 Implications for patient care
ADHD is not outgrown in older persons Impairment is not diminishing Similar prevalence rates across the lifespan (3-5%) Lifespan patient services are needed Case reports indicate similar response to medication as in adults and children RCTs needed in older people with ADHD using stimulants More research needed into the impact of ADHD with age on social, psychiatric and somatic functioning


46 Comorbidity in adults with ADHD
ADHD comes seldom alone: 75% at least one other disorder 33% two or more Mean: 3 comorbid disorders Biederman 1993; Kooij 2001, 2004

47 Comorbidity in ADHD? Depression (60% SAD) 20-55%
Bipolar Disorder (88% BP II) 10% Anxiety Disorders % SUD % Smoking % Cluster B Pers. Disorders % Sleeping Problems (DSPS) 75% Muscle, joint, neck- and backpain ?? Biederman 1991,1993, 2002; Weiss 1985; Wilens 1994; Kooij 2001, 2004; van Veen 2010; Amons 2006

48 The other way round: ADHD is comorbid in 20% of psychiatric patients
SUD: 20% (Trimbos Institute) Anxiety disorders: 20% (PsyQ) Bipolar II: 20% (PsyQ) Borderline PD: 35% (Radboud University) And in accordance to epidemiological data USA: 20% vd Glind 2005; Rops 2010 in prep; Roodbergen 2010 in prep; Fones 2004; van Dijk 2010 in prep; Kessler APA 2007; Fayyad 2007

49 12 month comorbidity with ADHD in adults, epidemiological study USA
OR % ADHD % comorbid D in comorbid D in ADHD _____________________________________________ Mood Ds 3.8* Anxiety Ds 3.8* SUDs 2.8* 1 Disorder 3.0* 2 Disorders 3.9* 3+ Disorders 8.3* Any disorder 4.4* Kessler, APA 2007

50 OR for comorbidity in active ADHD compared to ADHD, in remission
8,2* 6,2 3,9* 4,3* 3,9* 3,9 3,5 OR 2,5 1,6 1,2 Kessler, APA 2007

51 Conclusions Epidemiological study Kessler
1 in 5 mood disorders are comorbid with ADHD Depression is comorbid in 30% of ADHD ADHD has an earlier onset than mood, anxiety or SUDs ADHD is a riskfactor for a range of comorbid disorders Treatment/remission of ADHD leads to lower occurence of mood-, panic disorder, and PTSD Kessler APA 2007

52 ADHD or Borderline? Overlap Impulsivity is hallmark of both
Frequent moodswings & irritability in 90% of adults with ADHD Differential diagnosis Inattention and hyperactivity only in ADHD ADHD starts in childhood, borderline in adolescence Emptiness, manipulative behaviour, all good-all bad patterns specific to borderline History of neglect or sexual abuse typical in borderline, not ADHD Comorbidity 6-25% of adults with ADHD also have cluster B personality disorder 35% of borderline patients also have ADHD Kooij 2006; van Dijk in prep, 2009

53 Chance of addiction ADHD vs controls
Wilens, 2003

54 Substance Use Disorder: Age at onset in ADHD compared to controls
1 ADHD Controls 0.9 0.8 0.7 Likelyhood 0.6 p<0.05 0.5 0.4 0.3 This study evaluated the association between ADHD and the age of onset of psychoactive substance use disorders (PSUD) in adults with ADHD and tested the hypothesis that ADHD and psychiatric comorbidity would be risk factors for early onset PSUD 120 adults with a clinical diagnosis of childhood-onset ADHD were compared with 268 non-ADHD adults ADHD was associated with earlier onset of PSUD independently of psychiatric comorbidity ADHD with and without psychiatric comorbidity was associated with adolescent onset PSUD 0.2 0.1 10 20 30 40 50 60 Age at onset Wilens 1997

55 ADHD and SUD Medication treatment of ADHD does not increase chance of SUD Research suggest a protective effect of stimulants against substance abuse Wilens 2003

56 ADHD & the circadian rhythm in adults with ADHD Implications for sleep, mood and health
J.J. Sandra Kooij, MD PhD Psychiatrist, Head Dutch Expertise Center Adult ADHD, PsyQ, psycho-medical programs The Hague, The Netherlands

57 Adult ADHD is highly comorbid with circadian based disorders
75% has comorbidity (mean 3 disorders): Depression (60% SAD) % Anxiety % Substance Use Disorders 20-45% Personality Disorders 6-25% Eating Disorders (BN) 9% Binge eating 86% Obesity % Sleepproblems, DSPS pattern 75% Kooij 2001 NTG;145(31): ; Kooij 2004, Psychol Med;34(6):973-82, Kooij 2012, book Adult ADHD; van Veen 2010, Biol Psychiatry 67(11): ; Biederman 1993, AJP;150(12):1792-8; Kessler 2006, AJP;163(4) :716-23; Pagoto 2009, Obesity;17(3): Davis 2009, J Psychiatr Res;43(7): Kooij & Bijlenga, in press.

58 ADHD and sleepproblems in children
Corkum 1998, JAACAP;37(6):637-46;Corkum 1999, JAACAP;38(10): ; Corkum 2001, Sleep;24(3):303-12; Konofal 2007, Sleep Med;8(7-8):711-5; Philipsen 2006, Sleep Med Rev, 10(6): ; Gaultney 2005, Behav Sleep Med;3(1):32-43; Lecendreux 2000, J Child Psychol Psychiatry;41(6):803-12; Golan 2004, Sleep;27(2):261-6; Boonstra 2007, Sleep;30(4):433-42; Oosterloo 2006, Psychiatry Res;143(2-3):293-7; van der Heijden 2005, Chronobiol Int;22(3): Van der Heijden 2006, J Sleep Res;15(1):55-62 ; Sobanski 2008, Sleep;31(3):375-81; Sadeh 2006, Sleep Med Rev;10(6): Subjective measures: Sleep onset latency / bedtime resistance Difficulty waking up Fragmented sleep Decreased sleep efficiency Excessive daytime sleepiness Objective measures (MSLT, actigraphy, PSG, DLMO): Excessive Daytime Sleepiness (EDS) Periodic limb movement disorder (PLMD) / Restless Leg Syndrome (RLS) Reduced % REM sleep Obstructive Sleep Apnea Syndrome (OSAS) Delayed Sleep Phase Syndrome (DSPS): DLMO 45 min delayed

59 Sleep questionnaire in 120 adults with ADHD
Difficulty … going to bed on time: 78% falling asleep: % sleeping through: 50% getting up in the morning: 70% daytime sleepiness: 62% This pattern lifetime in 60%, suggestive of Eveningness or Delayed Sleep Phase Syndrome Kooij, Society of Light Treatment and Biological Rhythms 2007

60 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!)

61 Sleep phase delay in ADHD
Melatonin level Time

62 40 consecutive ADHD patients
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%) Alcohol (U/wk) 6.76 5.67 Nicotine (Sig/day) 8.16 1.11 Sleep diagnosis ns Van Veen 2010, Biological Psychiatry;67(11):

63 Dim Light Melatonin Onset (DLMO): delayed N=40 adults with ADHD w/wo Sleep Onset Insomnia versus healthy controls ADHD Total SOI no-SOI HC p: ADHD vs HC p: DLMO (hr ± sd) 22:57 ± 1:20 23:15 ± 1:19 22:00 ± 0:54 21:34 ± 0:45 0.000 Melatonine onset: duidelijk verschillend - sterk verlaat op gang komen van melatonine productie bij ADHD 83 minuten later verschil zit mn in SOI groep n = 26 vs 8 vs 28 5 patienten onvoldoende speeksel 5 van 26 onset na 01:00 1 van 26 en 3 van 8 voor 21:00 als je deze conservatieve schattingen eruit laat: dan nog steeds zeer significante verschillen We measured summer and winter, evenly distributed along groups, and the average day length did not differ between groups (around 13 hrs) en geen correlatie DLMO met daglengte - 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

64 24 hour movement patterns ADHD + SOI compared to controls (actigraphy)
Combinatie voorgaande slides: 24 uurs activiteit - uitleg lijnen 24 hr rhythm shifts by about 1 hour backwards SO / SE SOI groep vergeleken met no-SOI en HC amplitude: SOI minder actief overdag en meer actief in de nacht In this graph : real resting period at night seems shorter and less deep And now our main outcome: dim light melatonin onset Van Veen ea 2010 64

65 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

66 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

67 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

68 Nucleus supra chiasmaticus (NSC): the biological clock
Hypothalamic nucleus, just above the chiasma opticum

69 ADHD, circadian rhytm, sleep, mood and season
100% DSPS 75% Over weight 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): Bijlenga 2013, J Att Disord; 17(3):261-75 Bijlenga 2013, J Sleep Res. Aug 16 epub SAD 30% BP II 10%

70 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):

71 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): ; Hansen 2001, J Natl Cancer Inst;93(20):1513-5; Blask 2005, Endocrine;27(2): Moser 2006, Conf Proc IEEE Eng Med Biol Soc;1:424-8; Verkasalo 2005, Cancer Res;65(20):

72 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

73 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

74 Hypothesized relations
Ramsey & Bass 2009, Proc Natl Acad Sci USA;106(11): ; Rüger 2009, Rev Endocr Metab Disord;10(4): Kooij 2012 74

75 ADHD index predicts weight and binge eating
Binge eating group Obese group Probability Normal weight group ADHD index CAARS Davis 2009, J Psychiatr Res;43(7):687-96

76 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 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):

77 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): Spiegel 2005, J Appl Physiol;99(5): ; Copinschi 2005, Essent Psychopharmacol;6(6):341-7; Shea 2005, J Clin Endocrinol Metab;90(5): ;

78 Sleep duration USA 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

79 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 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

80 Lewy 2005, 2006, continued; Kooij 2012 Book Adult ADHD
Melatonin treatment To fall sleep: 3 mg at 22:00 in order to sleep at 23:00 To reset the clock: 0.1 mg 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

81 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 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

82 Adult ADHD Diagnostic Assessment and Treatment
Including DIVA 2.0 JJS Kooij, 3rd edition 2012 Search for ‘Adult ADHD’

83 Outline Diagnostic Assessment
Early onset in life Chronic persistent course Chronic impairment or compensation/coping causing secondary impairment Mainstay of ADHD diagnosis is: CHRONICITY The period that ADHD symptoms are remembered will be longest in older adults

84 DIVA 2.0 Diagnostic Interview
Ongoing translations, now 15 languages Available DIVAs: Danish Dutch Catalan English Finnish French German Italian Norwegian Romanian Swedish Spanish Turkish Portuguese Brazilian Portuguese Next: Hebrew Japanese Iranian Italian translation: Luana Salerno & Stefano Pallanti Emphasize it can be used in adolescents 84

85 Diagnostic Assessment
3 hour interview with patient, spouse and family (DIVA) Childhood onset and lifetime ADHD symptoms and impairment Comorbidity Order and content of proposed treatment

86 DIVA 2.0 DIVA 2.0 has been developed to facilitate appropriate and careful diagnostic assessment of ADHD in adults DIVA-5 will be developed in 2014 This semi-structured diagnostic instrument still needs interpretation by a (trained) clinician DIVA 2.0 should therefore not be used by patients for selfreport

87 ADHD is a clinical diagnosis
Interview patient and partner: lifetime symptoms and impairment of ADHD and comorbid disorders School reports if available If possible, parents/sibs about childhood onset Patient is best informant, though tends to underreport severity No neuropsychological diagnostic test (battery) No validated instruments in Europe Kooij 2003, 2008; Ferdinand 2004

88 Treatment of ADHD in adults
Psycho- education Medication for ADHD and comorbid disorders Coaching / Cognitive Behaviour Therapy Light therapy for SAD and delayed sleep Support or Advocacy Groups Safren 2005, Weiss 2003; Kooij 2003

89 Medication Proven Effective for ADHD
Stimulants - Methylphenidate (short and longacting) - Dex-amphetamine (short and longacting, combination preparations) Atomoxetine Bupropion XL Modiodal Tricyclic antidepressants

90 Place of medication in treatment
Medication is very effective and comes first after psycho-education 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

91 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

92 Methylphenidate (Mph)
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

93 Combination treatment the rule in adult ADHD
75% of adult ADHD patients has comorbidity mostly sleep problems, anxiety, depression or SUDs Combined treatment is the rule rather than the exception

94 Light therapy and ADHD 5 days – 30 min – 10.000 lux – 40 cm:
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

95 Psychological treatment
‘Coaching’: practical, supportive and directive, similar to cognitive behaviour therapy interventions: 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

96 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

97 Adults want help PsyQ, in the Hague and in the Netherlands:
1300 patients in the Hague, only local referrals Mean age 38 yrs Males: females = 1.5 : 1 PsyQ currently has now 28 locations and teams around the country Most referrals at new locations are for adult ADHD (40-50%): unmet need … Rapid increase in expertise and availability of patient care for adult ADHD in the Netherlands

98 The ADHD Lifespan Clinic

99 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

100 Current organisation of Mental Health Care for ADHD
General Child Psychiatry General Adult Psychiatry General Psychiatry for older people

101 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

102 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

103 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

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

105 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!

106 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

107 10 year Anniversary of (the 28) PsyQ Programs Adult ADHD in the Netherlands, October 2013

108 AIMS AND ACTIONS Raising awareness that ADHD is a lifelong condition
Improving diagnosis and treatment in Europe (Consensus Statement, conferences, publications, European textbook, DIVA 2.0 translations) Ongoing research and development Increasing availability and access to services Italian representatives: prof. Pallanti & Luana Salerno


110 Conclusions Treatment of ADHD requires a lot of effort, no one can do it alone ADHD treatment needs a specialised multi-disciplinary team, best in lifetime perspective After spreading the word to the media and patient organisations, The unmet need will lead to a rapid increase of requests for diagnosis and treatment Start educating young professionals from the beginning Cooperate and support each other nationally, i.e.: How is your Italian ADHD Network doing? Dedication, not money is the most important factor for success

111 For patient driven & patient oriented research
First online questionnaire inventarising most needed subjects from both patients and researchers Preferred research subjects (n=219): ADHD and Mood, Health, ASS, and Sleep) Patients determine which research will be funded: patient empowerment!

112 Independent, no sponsoring pharma
Researchers determine research, based on patients’ preferences, and contribute as well Limited time to get funded, private and professional networks get involved Only succesful when large crowd of people is involved, international, worldwide fund Independent, no sponsoring pharma Started: April 2014 at Follow ADHDFund at Facebook and Twitter!

113 4th UKAAN CONGRESS: Mind, Brain and Body Sept 10-12, 2014
London UKAAN, European Network Adult ADHD & APSARD

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