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• Slide Presentation for the lecture of: Jeremy TurkSouth London & Maudsley NHS Foundation Trust, UK

• Topic of lecture: Sleep Disorders in Children and Adolescents with Developmental Disabilities and their Managements

• The lecture was given at Beit Issie Shapiro’s 6th International Conference on Disabilities - Israel

• Year: 2015

Sleep Disorders in Children & Young Sleep Disorders in Children & Young People with Developmental People with Developmental DisabilitiesDisabilitiesJeremy TurkJeremy TurkAcademic Child & Adolescent Mental Health,Academic Child & Adolescent Mental Health,Institute of Psychiatry, King’s College, University of LondonInstitute of Psychiatry, King’s College, University of London&&Child & Adolescent Mental Health Neurodevelopmental Services,Child & Adolescent Mental Health Neurodevelopmental Services,South London & Maudsley Mental Health Foundation NHS TrustSouth London & Maudsley Mental Health Foundation NHS Trust

Turk, J. (2010)Turk, J. (2010)

Sleep Disorders in Children & Adolescents Sleep Disorders in Children & Adolescents with Learning Disabilities & Their with Learning Disabilities & Their

ManagementsManagements

Advances in Mental Health & Learning Advances in Mental Health & Learning DisabilitiesDisabilities

Volume 4, Issue 1, Volume 4, Issue 1, pp. 50-59.pp. 50-59.

Turk, J. (2014)

Use of Medication in Children & Young People with Intellectual Disability & Challenging

Behaviours

“Intellectual Disabilities & Challenging Behaviour”ACAMH Occasional Papers No. 32

(eds: Lovell, M. & Udwin, O.)

London: Association for Child & Adolescent Mental Healthpp. 36-44.

Common Sleep DifficultiesCommon Sleep Difficulties Insomnia

Settling difficulties

Recurrent night time waking

Early morning waking

Nightmares, night terrors, sleep talking, sleep

walking, sleep reversal, sleep paralysis

Sleep disorders in childhoodSleep disorders in childhood 15-20%, Isle of Wight study May be– Settling difficulties (“sleep induction”)– Repeated night-time waking– Early morning waking– Parasomnias e.g. sleep walking, night terrors

Strong association with– daytime behavioural difficulties– maternal stress & depression– Family discord & parental separation– Poor educational attainments & socialisation

QUINE 1991:QUINE 1991:Longitudinal study of sleep disturbance in 200 young

people with moderate-to-profound intellectual disability

51% settling problems

67% waking problems

32% of parents reported rarely getting enough sleep

Sleep & Autism Spectrum Conditions:Sleep & Autism Spectrum Conditions:44-83% sleep disturbanceSubjective & objective difficulties

- Falling asleep- Staying

Biochemical & genetic associations- Low plasma & saliva melatonin levels

? Low melatonin CNS receptor sensitivity? Lack of circadian secretion rhythm

Behavioural TechniquesBehavioural TechniquesExtinction

Positive reinforcement +/- fading

Shaping & graded approaches

Antecedent contingencies

Discriminant Learning

Regular, structured, predictable & calming bedtime routine

Sleep determinants:Sleep determinants:Primarily social in people with average intellectual

abilities

– “zeitgebers”

Strong neurological components in children and young

people with developmental disabilities

Melatonin Melatonin (Turk, 2003; Turk, 2010)(Turk, 2003; Turk, 2010)N-acetyl-5-methoxytryptaminePineal indolediurnal secretion variationwidely available as food supplement in North America

unlicensed for children & young people in U.K. - only prescribable on named patient basis

Tryptophan

Serotonin

N-acetylserotonin

Melatonin(N-acetyl-5-methoxytryptamine)

JAN ET AL 1994:JAN ET AL 1994: 15 children, most with multiple neurological 15 children, most with multiple neurological

disabilitiesdisabilities improved sleepimproved sleep ““significant health, behavioural & social significant health, behavioural & social

benefits”benefits”BUTBUT

responses not always completeresponses not always complete responses varied considerably depending on responses varied considerably depending on

type of sleep disturbancetype of sleep disturbance not double-blindnot double-blind

JAN & ESPEZEL 1995:JAN & ESPEZEL 1995: Subsequent reportSubsequent report full or partial correction of sleep-wake cycle full or partial correction of sleep-wake cycle

disturbance in almost 90 children with a range disturbance in almost 90 children with a range of developmental disabilities, neurological of developmental disabilities, neurological disorders & chromosomal anomaliesdisorders & chromosomal anomalies

continuing strict environmental sleep continuing strict environmental sleep structuring importantstructuring important

side effects & tolerance not notedside effects & tolerance not noted

MELATONIN IN SPECIFIC MELATONIN IN SPECIFIC GENETIC DISORDERS:GENETIC DISORDERS: O’Callaghan et al. 1999:O’Callaghan et al. 1999:

7 individuals with 7 individuals with tuberous sclerosis tuberous sclerosis and and severe sleep problemssevere sleep problems

small but significant improvement in total sleep small but significant improvement in total sleep timetime

non-significant improvement in sleep onset non-significant improvement in sleep onset timetime

? Responders & non-responders? Responders & non-responders McArthur & Budden 1998:McArthur & Budden 1998:

improved sleep-onset latency, total sleep time improved sleep-onset latency, total sleep time & sleep efficiency in 9 individuals with & sleep efficiency in 9 individuals with Rett Rett syndromesyndrome

Gringras et al., 2012Gringras et al., 2012 Randomised double masked placebo controlled trial for sleep

problems in children with neurodevelopmental disabilities 146 children aged 3-16 Total sleep time by 22.4 minutes Sleep onset latency by 37.5 minutes Melatonin earlier waking times than placebo Children fell asleep significantly faster But woke earlier And gained little additional sleep on melatonin Child behaviour & family functioning outcomes favoured melatonin but

were not significant But parents loved it!

Melatonin is:Melatonin is: Highly beneficial, short-term, rapid-onset & safe treatment for intractable

sleep disturbance Therapeutic dose not predicted by:– severity of sleep disturbance– severity of intellectual disability– presence/absence of autism

Habituation common but not universalConcomitant psychological, behavioural, educational, family & social

interventions essentialNo obvious short-term adverse effects but long-term safety has not been

confirmedNo adverse effects other than habituation up to 5 years after

commencement Modified-release version (Circadin) probably no better than immediate-

release – but cheaper!

Other Options:Other Options:α-2A noradrenergic receptor agonists– Clonidine, Guanfacine– Lack appetite and sleep disturbance– Good for tic disorders– But sedation & ↓ blood pressure

Tricyclic antidepressants– Imipramine, Amitriptyline– Good for anxiety, depression, enuresis, tics, insomnia– May need to do ECG

? Calming SSRIs – as above

Clonidine Clonidine (Ingrassia & Turk, 2005)α2A noradrenergic receptor agonistShown efficacy for anxiety, overactivity, impulsiveness,

inattentivenessMildly sedating, mildly hypnoticGood for tics & Tourette’sGood for repeated night time wakingNo effect on appetiteCan drop your blood pressure25-300 μg daily in divided doses

Acebutolol:Acebutolol:selective beta-1 adrenergic agonist De Leersnyder et al (2003)melatonin antagonistnine children with Smith-Magenis syndromesevere and intractable sleep difficultiessuccessful suppression of inappropriately high morning

melatonin levels improved behaviour and concentration, a reduction in

delays in sleep onset, increased sleep duration and delayed waking

Suggestion of usefulness in Prader-Willi syndrome – but exclude sleep apnoea first!

Puttaswamaiah & Turk (2015)Puttaswamaiah & Turk (2015)Prader-Willi Syndrome & dysfunctional sleep-wake cycle

Asleep mid-afternoon on return from schoolAwake early night and thereafterNo response to behavioural approachesNo response to evening melatoninStriking, rapid improvements with mid-afternoon acebutolol

AnxietyAnxietySSRIs especially mildly calming & sedating ones e.g. sertraline, citalopram

Beta blockers e.g. propranololAlpha agonists e.g. clonidineIn extremis, low-dose short-term risperidone – can commence as low as 0.125mg twice daily

Anticonvulsant Mood & Behaviour Anticonvulsant Mood & Behaviour Stabilisers:Stabilisers:Carbamazepine, sodium valproate, lamotrigineExcellent anticonvulsants with good safety profilesBeneficial in bipolar/cyclical mood disordersEmerging evidence base for child & adolescent

fluctuating mood disordersNow used increasingly for cyclical (and not so cyclical)

mood and behaviour challenges in children & young people with complex, multiple & severe developmental disabilities

Balancing mood & behaviour can enhance sleep.

Clinical GuidelinesClinical GuidelinesAlways commence with sleep hygiene measures & behavioural approaches

Sleep induction: melatoninSleep maintenance: clonidineEarly morning waking (especially in association with anxiety or mood disorder: sedating SSRI

In extremis, low-dose short-term risperidone – can commence as low as 0.125mg

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