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The need for better long term outcomes -
personalised assessments, and treatments
ADHD
The Circadian Sleep-Wake cycle
N e u r o f e e d b a c k
Mark Ryan*, Trevor Brown* & Martijn Arns**n e u ro C a re A u s t r a l i a * and n e u r o C a r e M u n i c h **
Research Institute Brainclinics & Utrecht University, The Netherlands**
What we see is biased by what we believe/expect/predict to see
In this presentation the aim is to introduce some new beliefs/expectations about ADHD to enable seeing and treating it differently
Steps along the way to expanding attention and perception about inattention etc:
Efficacy & effectiveness of ADHD treatments
short and long term outcomes
Sleep, ADHD and neurofeedback
the causal role of sleep disorders &
effective treatment with neurofeedback
Cognitive & Behavioural Treatments & Medications
An overview of efficacy
Sonuga-Barke et al. (2013)
Psychological & non-pharmacological treatments for ADHD: Proximal treatment Outcomes
The conditionality of treatment efficacy of medication Medication and behaviour therapy - MTA Trial
Short term condition - remission rates 25-68%
* 68% combined CBT + meds
* 56% meds only
* 25% CBT & community treatment arms (+meds) = TAU
initial large ES shrinks by 14 months
Longer term condition - further shrinking; initial benefit not sustained
* @ 3yrs, initial advantage of meds over behavioural therapy disappears (Jensen et al., 2007)
* @ 8 yrs, no advantage of medication over other treatments (Molina et al.,2008; Swanson et al., 2018)
Medication does not improve outcomes in the longer term: ADHD patients continued to lag behind non-ADHD on academic & mental health measures (Molina et al., 2008; Swanson et al.; 2017)
Wang et al. (2013)
Up-regulation of dopamine transporter availability with continued use of Ritalin (Wang et al., 2013)
Well known stimulant medications side effects include : appetite and mood problems common (Cascade et al., 1010; McDonagh et al., 2017)
: reduced adult height (Swanson et al., 2017)
Both stimulant and non-stimulant meds (atomoxetine) reduce electric power in sleep EEG & alter CLOCK gene expression : : disrupts entrainment & amplitude of the diurnal circadian rhythm : resulting in prolongation SOL, increased nocturnal activity, reduced sleep duration and quality with more WASO (Boonstra et al., 2007; Coogan et al; in press)
Medication treatment outcomes in ADHD: receptor up-regulation and sleep
PET - dopamine transporter
N e u r o f e e d b a c k
An overview of efficacy: a closer look
Neurofeedback & ADHD: Treatment OutcomesSHORT-TERM EFFECTS
RCTs, cf semi-active control groups, ‘standard neurofeedback protocols’
Large ES for inattention & impulsivity
Medium ES for hyperactivity
32-47% remission rate (Arns et al., 2009)
More recent RCTs - Duric et al., 2012; Meisel et al., 2013
Theta/Beta Neurofeedback as effective as methylphenidate in reducing all ADHD symptoms
BUT superior academic performance (2 RCTs @
30-40 Neurofeedback sessions; no evidence for nonstandard protocols (e.g. Z-Score & LORETA NFB (Coben et al., 2018)
LONG-TERM EFFECTS All NFB studies show benefits persist / further improvement (ES) in the follow-up period after course of
Neurofeedback cf, medication effects
confirmed in a recent systematic review & meta-analysis
(Van Doren et al., 2018)
Effectiveness of treatment: Beyond the RCT, how well does it actually work in
everyday clinical practice
Purely statistical evidence is never enough
Medications & neu ro feedback
A comparison of effectiveness in everyday clinical practice
MTA Medication
In open label trials and clinical practice, medication benefits much lower than the original MTA trial results
ISPOT-A ** - open label multi-centre trial, included Australian centres; MTA algorithm used as control (Arns et al., 2018; Elliott et al., 2017)
the MTA 56-68% remission rates drop to 31%
loss of effect of medicat ion over t ime
Neurofeedback
Large ES with a remission rate of 53% in the clinical setting, using QEEG informed ‘standard NFB protocols’ (Arns et al., 2012)
NFB (standard protocols) translates well into clinical practice with efficacy similar to multicomponent behaviour therapy arm of MTA and only marginally below MTA medication arms
Currently in the NeuroCare clinics across the world we are achieving a 55% remission rate, based on the very strict Swanson et al (2001) criteria#
**
Conclusion: standard neurofeedback protocols achieve
clinically relevant benefits and better long-term outcomes C l i n i c a l b e n e f i t o f M TA m e d i c a t i o n a r m s n o t a c h i e v e d i n c l i n i c a l p r a c t i c e (Arns et al., 2018; Elliott et al., 2017).
Medication does not achieve long term maintenance of remission of symptoms of ADHD (Molina et al.,2008; Swanson et al., 2017).
Standard Neurofeedback protocols (SMR, Theta/Beta & SCP) translate well into cl inical practice achieving an effectiveness similar/better relat ive to medication in MTA Trial (Arns et al., 2012; Arns et., 2018; Elliott et al., 2017).
Neurofeedback benefits persist beyond cessation of NFB, with further improvement in the follow up period (Van Doren et al., 2018)
NFB is both non invasive and safe - no significant NFB specific side effects reported in the literature (Strehl et al., 2017)
What is neurofeedback?
Evidence based neurofeedback is the operant training of EEG activity using ‘standard protocols’
Effective Neurofeedback requires adequate training of the therapist and
strict adherence to principles of operant learning* & adequate intensity and duration of
treatment
Standard neurofeedback protocols, are efficacious and specific in the treatment of ADHD(Level 5 evidence; Updated APA Guidelines - Arns, Heinrich and Strehl., 2016)
Not neurofeedback: ‘double sham’
(2017)
Neurofeedback - the importance of doing it correctly = standard protocols and operant learning principles
So, what about sleep? Sleep as a biomarker
Sleep disorders in ADHD lurking in plain sight
What has neurofeedback got to do with it?
Common sleep problems in ADHDObstructive sleep apnoea - 20% prevalence (Silvestri et al., 2009)
Restless legs - 26% prevalence (Konofal et al, 2010; Silvestri et al, 2009)
Delayed onset circadian rhythm sleep disorder (sleep onset insomnia) ~ 80% prevalence and diurnal dysregulation of cortisol and melatonin (van der Heijden et al 2005: 2007: van Veen et al, 2010)
ADHD children deficient in sleep spindles (12-15Hz) (Saletin et al., 2017)
Gene-environment interactions
High prevalence (>40%) of evening chronotype - ‘night owl’ (Rybak et al., 2007) - more susceptible to sleep restriction due to poor sleep hygiene and social demands etc
Lower prevalence of ADHD in regions of higher solar intensity (Arns et al., 2013)
Sleep-Wake disturbances and ADHD 1. shorter sleep duration
Skimping on sleep - our dark deprived urban night time environment, social demands & lifestyle
self reported sleep duration declined > 1.5-2.0 hours/night in last 50 years (National Sleep Foundation in America poll, 2015)
children sleeping 75 minutes/night less than 100 years ago (Matricciani et al., 2012)
shorter sleep duration/sleep restriction in children & adolescents correlates with
reduced school performance impaired executive functioning, mood dysregulation, behavioural impulsivity and internalising and externalising behaviour problems (Astil et al, 2012: meta-analysis N = 35936; van Dongen et al., 2003)
ADHD symptoms in both healthy (Axelsson et al., 2008; Belenky et al., 2003: van Dongen et al., 2004; Calhoun et al.,
2017; Gau et al., 2007; Kass et al., 2003) and ADHD groups (Mahajan et al., 2010; Arns & Vollebregt., 2019; Becker et al., 2018)
Shorter sleep duration is causal of inattention in those with and without ADHD (Becket et l., 2018; Arns and Vollebregt., 2019)
Melatonin improves sleep onset but not cognitive performance and behaviours in short-medium term (Van der Heijden et al., 2007)
Early morning bright light improves mood and ADHD symptoms (Rybak et al, 2006)
8 9 10 11 1270.5
1.0
1.5
2.0
2.5
3.0
Conn
er’s
inat
tent
ion
(Tea
cher
)
Amount of sleep (hours)Sleep onset delay (onset longer than 20 minutes)
No Yes7
8
9
10
11
12
Amou
nt o
f sle
ep (h
ours
)
12
3
6
9
Slee
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elay
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No
Yes
% LED light <50≥50
++
-- -
-
d=0.390
OR=2.28
R2=3.4
a.
b.
LED (blue) l ight exposure at night positively associated with the amount of sleep onset delay (> 20 minutes)
which in turn is negatively related to sleep duration which leads to worsening of attention blue l ight also penetrates the closed eyelids
Adolescent ratings - no reports of inattention; Teacher ratings - attention worse, more oppositional
Sleep restriction & ADHD: the causal role of blue light at night
Sleep-Wake disturbances and ADHD 2. disordered sleep breathing
Disordered breathing in sleep - OSA and snoring without obstruction
adenotonsillectomy substantially improves attention and ADHD behaviours (Huang et al, 2007; Swedky et al., 2016)
cpap use results in improved ADHD symptoms (Johnstone et al.,2001)
disturbed sleep breathing - snoring without OSA also disrupts sleep quality
and is associated with ADHD symptoms (Sedky et al., 2014) and particularly with hyperactivity/impulsivity in ADHD (Silvestri et al., 2009) and in the general population (Bonuck et al., 2012)
Disrupted sleep & ADHD: the role of disordered breathing
*Sleep apnoea an exclusion criteria
The inside-out of ADHD The circadian pathway model*
*Arns & Kenemens (2012)
ATTENTION DEFICIT / HYPERACTIVITY DISORDER
Hyperactive subtype Combined Subtype Inattentive Subtype
Unstable Vigilance Regulation (trait-like)
Sleep disordered breathing /Circadian Phase delay & restricted sleep duration
Vigilance Autostabilisation Syndrome(e.g. hyperactivity, sensation seeking,
talkativeness)
Cognitive Deficits(e.g. impaired sustained attention
NUMEROUS BRAIN AND BODY FUNCTIONS ARE RESTORED & REGULATED IN SLEEP – INSOMNIA AS A 24/7 DISORDER
Necessary for memory & learningDuring sleep we process memories and learning from the day - lack of sleep affects long-term and short-term memories and learning. Regulates emotions, steadies mood swings; we process emotional experiences in sleep; enabling us to cope and emotionally regulate better
Improves concentrationOur attention/concentration, motivation, energy and learning are reduced when we have not slept enough
Important to get good night’s sleep before and after any therapy!
Adequate sleep enhances and generalises learning (e.g.) fear response to stimulus addressed in therapy.
Lack of sleep reduces benefits of medications, psychotherapy, and of course neuromodulation therapies.
CRSD predicts non response to rTMS for OCD and is the major causal factor for most with ADHD
Restores, Repairs & Resetsmuscle recovery; BP reset; metabolic reset; hormone secretion; restores the immune system; drains beta amyloid from the brain
Improves social behaviour & occupational performance; Lack of sleep means we are less likely to correctly ‘read’ emotion and social cues/ feelings of others; less able to be empathic; less efficient and productive, make more errors
Improves behaviour & sporting performance; Lack of sleep results in irritability, impulsivity and disruptiveness; better sleep meansbetter sporting and other performances
30
For adequacy of awake state functioning Sleep is necessary for everything
W h i l e c a u s a l i t y i s n e v e r o n e t h i n g , b u t m a n y, s l e e p i s t h e m a j o r c a u s a l f a c t o r i n t h e
l a rg e s t s u b g ro u p w i t h A D H DNew DSM category? - “ADHD-SOM” - where sleep problems largely explain ADHD symptoms (Arns & Vollebregt, 2019)
sleep assessment and personalised treatment of sleep key to optimal outcome
Adolescents, sleep restriction & social demands: a particular concern (aggravates the adolescent circadian phase delay and CRSD)
increased SWS intensity in which synaptic pruning occurs begins posteriorly & progresses frontally (mirrors psychosocial development)
Disruption of this process resulting in abnormal synaptic & connectome development associated with risk of SZO, depression
caffeine, alcohol, stimulant use, further disrupt sleep, attention, mood and other self-regulation, learning and synaptic pruning
Summary: Sleep, ADHD and neurofeedback
A D H D s y m p t o m s c a n b e c a u s e d b y s l e e p p r o b l e m s ; t r e a t i n g t h e s l e e p p r o b l e m s c a n r e m i t A D H D s y m p t o m s & b e h a v i o u r s [Arns et al., 2012; Arns and Kenemans., 2012; Duric et al., 2012; Meisel et al., 2013]
S t a n d a r d N e u r o f e e d b a c k p r o t o c o l s a r e e f f i c a c i o u s , e f f e c t i v e a n d s p e c i f i c i n t h e t r e a t m e n t o f A D H D ( L e v e l 5 e v i d e n c e ; Updated APA Guidelines - Arns, Heinrich and Strehl., 2016)
S M R N e u ro f e e d b a c k e f f e c t s a re m e d i a t e d
b y n o r m a l i s a t i o n o f s l e e p o n s e t l a t e n c y ( A r n s e t a l . , 2 0 1 4 )
the e f fects o f neuro feedback are susta ined a t fo l low up wi th fu r ther ga ins a f te r neuro feedback t reatment has s topped ( Va n D o re n e t a l . , 2 0 1 8 )
New DSM category proposed: “ADHD-SOM” where ADHD symptoms can be largely explained by sleep problems (Arns & Vollbregt., 2019; Bijlenga et al., 2018)
Poor sleep duration / efficiency Impaired daytime vigilance ADHD-like symptoms
Psychostimulant medictions
ADHD medications adversely impact
on the electrical quality of sleep and
also the molecular clocks regulating circadian rhythm and sleep-wake
regulation [Korman et al., 2018]
Benefits of medication not sustained
over the longer term and do not
improve long term outcomes [Jensen et
al., 2007; Molina et al., 2008; Swanson et
al., 2017]
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