+ All Categories
Home > Documents > The Pediatric Sleep Disorders

The Pediatric Sleep Disorders

Date post: 05-Aug-2016
Category:
Upload: herbert-wertheim-college-of-medicine
View: 220 times
Download: 1 times
Share this document with a friend
Description:
The International Symposium on Primary Care July 2, 2016
71
Pediatric Sleep Disorders: Evidence Based Use of Medications For The Primary Care Physician Daniel Castellanos, MD Assistant Dean for Graduate Medical Education Founding Chair, Department of Psychiatry & Behavioral Health; Professor of Psychiatry & Behavioral Health and Pediatrics Herbert Wertheim College of Medicine, Florida International University
Transcript
Page 1: The Pediatric Sleep Disorders

Pediatric Sleep

Disorders: Evidence

BasedUse

ofMedications

ForThe

PrimaryCare

Physician

Daniel Castellanos, MDAssistant Dean for Graduate Medical Education

Founding Chair, Department of Psychiatry & Behavioral Health; Professor of Psychiatry & Behavioral Health and Pediatrics

Herbert Wertheim College of Medicine, Florida International University

Page 2: The Pediatric Sleep Disorders

Disclosures

Consultant, Florida Medicaid Drug Therapy Management Program for Behavioral HealthUniversity of South Florida/AHCA

No other relevant financial disclosures

Castellanos 2016

Page 3: The Pediatric Sleep Disorders

Castellanos 2016

I. Identify of pediatric sleep disorders

II. Recognize non-pharmacologic management of pediatric sleep issues

III. Identify medication treatment of these disorders, with emphasis on evidence based use of medications.

Learning Objectives

Page 4: The Pediatric Sleep Disorders

Castellanos 2016

I. Overview

of pediatric

sleep disorders

Page 5: The Pediatric Sleep Disorders

Castellanos 2016

Page 6: The Pediatric Sleep Disorders

Castellanos 2016

Overview of

pediatric sleep

disorders

Pediatric sleep disorders represent highly common phenomena that often interfere with daily patient and family functioning

Dysomnias

Parasomnias

Page 7: The Pediatric Sleep Disorders

Castellanos 2016

Overview of

pediatric sleep

disorders

Dyssomnias

Patients with dyssomnias present with difficulty initiating or maintaining sleep or with excessive daytime somnolence.

Insomnia disorder (DSM-5) - primary insomnia (DSM-IV)

Includes changes with normal sleep efficiency, sleep-wake cycles, and sleep architecture.

This may be a lifelong pattern.

Defined as primary disturbances in the quantity, quality, or timing of sleep.

Page 8: The Pediatric Sleep Disorders

Castellanos 2016

Insomnia Disorder Criteria

The problems with sleep are often associated with the following:

Difficulty initiating sleep:

In children, this includes difficult initiating sleep without a caregiver.

Difficulty initiating sleep means that the subjective sleep latency is greater than 20-30 minutes.

Page 9: The Pediatric Sleep Disorders

Castellanos 2016

Insomnia Disorder Criteria

Difficulty maintaining sleep:

In children, this includes difficulty returning to sleep without caregiver

Difficulty maintaining sleep is the subjective time awake after sleep onset is longer than 20-30 minutes.

Page 10: The Pediatric Sleep Disorders

Castellanos 2016

Insomnia Disorder Criteria

Early morning awakening with difficulty returning to sleep.

There is no standard definition of early morning awakening, but it usually requires awakening 30 minutes before the scheduled time or before total sleep time reaches 6.5 hours.

Significant distress or impairment, occurring 3 nights per week, present for at least 3 months, and occurring despite sufficient time for sleep.

Page 11: The Pediatric Sleep Disorders

Castellanos 2016

Dyssomniavs

Parasomnia Parasomnias

Result in disruption of an existing state of sleep.

Include:

NREM sleep arousal disorders (Sleep terror disorder/Night terrors)

Nightmare disorder

REM sleep behavior disorder

Restless legs syndrome (RLS)

Page 12: The Pediatric Sleep Disorders

Castellanos 2016

Medications Used to Treat

Pediatric Sleep Disturbances

Meds Used to

Treat Insomnia

Page 13: The Pediatric Sleep Disorders

Castellanos 2016

Levels of Scientific Evidence

Randomized controlled trials

Non-randomized controlled trials; large meta-analysis

Observational studies with controls

Observational studies without controls; case series

Case reports; anecdotal reports; clinical consensus

Source: Adapted from US Dept of Health and Human Services; http://www.ahrq.gov/

Highest

Lowest

Page 14: The Pediatric Sleep Disorders

Castellanos 2016

Medications for

Sleep Disturbance

Melatonin

Diphenhydramine

Clonidine

Trazodone

Mirtazapine

Benzodiazepines

Amitriptyline

Page 15: The Pediatric Sleep Disorders

Castellanos 2016

Melatonin

Page 16: The Pediatric Sleep Disorders

Castellanos 2016

Melatonin

Melatonin is a hormone synthesized in the pineal gland from the amino acid, tryptophan.

Secretion of melatonin from the pineal gland is controlled by the hypothalamus, the site of the biological clock.

It appears in blood during the early evening, with peak concentrations occurring around 2.00–3.00 AM and then decreases to be undetectable by the time people are breakfasting.

Page 17: The Pediatric Sleep Disorders

Castellanos 2016

RCTs Melatonin Use in Children

Study NDuration

(days)Dosages Results

Type of Study

Smits et al (2001) 40 28 5 mg POS RCT

Smits et al (2003) 62 28 5 mg POS RCT

van Geijlswijk et al (2010)

70 70.05 mg/kg, 0.1 mg/kg, 0.15 mg/kg

POS RCT

Wilhelmsen-Langeland et al

(2013)

40(16-25 yo;

16/40 in HS)14 3 mg NS RCT

Saxvig et al (2014)40

(16-25 yo; 16/40 in HS)

14 3 mg NS RCT

Page 18: The Pediatric Sleep Disorders

Castellanos 2016

Other Studies Melatonin Use in Children & Adolescents

Study NDuration

(days)Dosages Results Type of Study

Ivanenko et al (2003) 32 60 2 mg POS Open label

Szeinberg et al (2003)

62 (adolescents)

180 3-5 mg POS Retrospective

Wilhelmsen-Langeland et al

(2013)

40(16-25 yo;

16/40 in HS)90 3mg POS

Open labelcontinuation

Saxvig et al (2014)40

(16-25 yo; 16/40 in HS)

90 3 mg POSOpen label

continuation

Page 19: The Pediatric Sleep Disorders

Castellanos 2016

Melatonin

13 controlled studies of melatonin for sleep disturbance in children with neurodevelopmental disorders (n = 424)

Dose 1-10 mg

Melatonin > placebo in all 13 studies

Multiple studies report increased speed of falling asleep & better sleep efficiency.

Adverse events = mild and similar to placebo

Source: Hollway and Aman Res Dev Disabil 32: 939-962, 2011.

Page 20: The Pediatric Sleep Disorders

Castellanos 2016

MelatoninSide

Effects

The most common melatonin side effects include:

Daytime sleepiness

Headaches

Dizziness

Less common side effects: abdominal discomfort, mild anxiety, irritability, confusion and short-lasting feelings of depression.

Page 21: The Pediatric Sleep Disorders

Castellanos 2016

MelatoninInteractions

Consider interactions with various medications, including:

Anticoagulants

Immunosuppressants

Diabetes medications

Birth control pills

Page 22: The Pediatric Sleep Disorders

Castellanos 2016

MelatoninSafety

There have been no appropriate studies to show that melatonin is safe in the long term for children.

Possibly safe vs unsafe. Because of its effects on other hormones, melatonin might interfere with development during adolescence.

Despite this, melatonin use has generally been regarded as safe by study authors and reviewers, despite the lack of rigorous clinical trials assessing its safety.

Page 23: The Pediatric Sleep Disorders

Castellanos 2016

MelatoninTypical hypnotic doses of melatonin are:

2.5 mg to 3 mg in children

5 mg to 10 mg in adolescents

No data for children under 2 yo

Melatonin is administered from 30 min to 60 min prior to the desired bedtime.

May find differences in response due to OTC proprietary brands.

.

Page 24: The Pediatric Sleep Disorders

Castellanos 2016

Melatonin

Chronobiological use:

Since melatonin is also associated with a hypnotic effect and a greater propensity to sleep, it has been suggested that exogenous melatonin could act as a chronobiological substance with hypnotic properties.

Its action will be more chronobiological or more hypnotic depending on the time when it is administered rather than on the administered dose, because it does not alter the total sleep time.

Page 25: The Pediatric Sleep Disorders

Castellanos 2016

Melatonin

Typical chronobiological doses of melatonin are:

0.3-6 mg in children & adolescents

No data for children under 2 yo

Administered up to 6 hours before the usual bedtime.

.

Page 26: The Pediatric Sleep Disorders

Castellanos 2016

Clonidine

Page 27: The Pediatric Sleep Disorders

Castellanos 2016

Clonidine

No controlled studies in children with sleep disturbance

Ming et al 2008: Open label trial of clonidine in ASD:

-decreased sleep latency by 2.2 hrs

-reduced night awakenings by 1.5

Clinical/anecdotal reports

No trials with guanfecine though might expect more sustained effect

Source: Ming et al. Use of clonidine in children with autism spectrum disorders. Brain Dev. 2008 Aug;30(7):454-60.

Page 28: The Pediatric Sleep Disorders

Castellanos 2016

May develop tolerance and develop mid-nocturnal awakening

Monitor BP and pulse

Avoid abrupt discontinuation

Guanfecine; clonidine ER

Clonidine

Page 29: The Pediatric Sleep Disorders

Castellanos 2016

ClonidineSide

EffectsThe most common clonidine side effects include:

Drowsiness

Dizziness

Dry mouth

Constipation

Less common: Fainting, irritability, depression, tachycardia, arrhythmia, rebound hypertension

Page 30: The Pediatric Sleep Disorders

Castellanos 2016

Clonidine 0.025 - 0.3mg qHS

Begin (0.1 mg) ½ to 1 tab at bedtime; increase by that amount weekly to 0.2 to 0.3 mg at bedtime

If no significant improvement in sleep after one week, begin increasing by ½ tab each week at hs until there has been a satisfactory improvement in the sleep disturbance, treatment-limiting side effects have emerged or a total daily dose of 0.3 mg has been reached.

Clonidine

Page 31: The Pediatric Sleep Disorders

Castellanos 2016

Diphenhydramine

Page 32: The Pediatric Sleep Disorders

Castellanos 2016

Diphenhydramine

5 controlled studies of diphenhydramine in persons (children & adults) with sleep disturbance

Results were mixed

Only ONE RCT (N=50) involving children

No RCTs since 1990

Can cause paradoxical worsening of sleep and behavior.

Page 33: The Pediatric Sleep Disorders

Castellanos 2016

DiphenhydramineChildren

Russo et al, 1976 randomized double-blind placebo-controlled trial (n=50)

Age 2-12 yo

Dose 1.0 mg/kg

Diphenhydramine was significantly better than placebo in:

reducing sleep latency

time and the number of awakenings per night

while sleep duration was marginally increased (NS)

Page 34: The Pediatric Sleep Disorders

Castellanos 2016

Other RCTs Diphenhydramine Use

Study Ages N Dosages ResultsType of Study

Sunshine et al (1978)Post partum

women557 12.5; 25; 50 mg POS RCT

Rickels et al (1983) 18-70 yo 111 1.0 mg/kg POS RCT

Borbély & Youmbi-Baldener (1988)

22-30 yo 10 50 or 75 mg NS RCT

Kudo & Kurihara(1990)

15-82yo 144 12.5; 25; 50 mg MIXED RCT

Page 35: The Pediatric Sleep Disorders

Castellanos 2016

DiphenhydramineSide

EffectsThe most common diphenhydramine side effects include:

Drowsiness

Dizziness

Constipation

Stomach upset

Blurry vision

Dry mouth/nose/throat

Less common: Restlessness or paradoxical excitement, confusion, difficulty urinating, tachycardia, arrhythmia

Page 36: The Pediatric Sleep Disorders

Castellanos 2016

Diphenhydramine

Starting dose: 12.5-25 mg

Titrate if necessary, based on response and body weight

Monitor for paradoxical worsening or excitement

Discontinuation: As clinical appropriate. No clear discontinuation parameters available

Diphenhydramine

Page 37: The Pediatric Sleep Disorders

Castellanos 2016

Mirtazapine

Limited evidence exists for the use of mirtazapine

No controlled studies in children with sleep disturbance

Open label trial in 26 ~1/3 responded with improved sleep, few side effects

Page 38: The Pediatric Sleep Disorders

Castellanos 2016

Mirtazapine:

Begin (15 mg) ¼ tab at bedtime; increase by this amount weekly to 3.75 to 45 mg at bedtime

Prominent adverse events are increased appetite, weight gain and sedation

Available in a soluble tablet

Mirtazapine

Page 39: The Pediatric Sleep Disorders

Castellanos 2016

Benzodiazepines

No controlled studies of benzodiazepines in children

Can cause paradoxical worsening of sleep and behavior.

Benzos can contribute to cognitive impairment and cause physical dependence

Page 40: The Pediatric Sleep Disorders

Castellanos 2016

Trazodone

No controlled studies in children with sleep disturbance

Begin (50 mg) ½ to 1 tab at bedtime; increase by this amount weekly to 25 to 300 mg at bedtime

Discuss potential adverse event of priapism

Page 41: The Pediatric Sleep Disorders

Castellanos 2016

Amitriptyline

No controlled studies in children with sleep disturbance

Begin (50 mg) ½ to 1 tab at bedtime; increase by this amount weekly to 25 to 300 mg at bedtime

Can lower the seizure threshold

Consider baseline electrocardiogram

Blood level available

Page 42: The Pediatric Sleep Disorders

Castellanos 2016

Herbal supplements

Chamomile, lavender, tryptophan, kava kava

Possible side effects: necrotizing hepatitis (kava kava); eosinophilia myalgia syndrome (tryptophan)

Use of herbal supplements have limited-to-no evidence of efficacy

Page 43: The Pediatric Sleep Disorders

Castellanos 2016

NOTE:

Use of antipsychotic meds, such as quetiapine (Seroquel®), is not recommended for the management of insomnia due to the potential metabolic side effects.

Insomnia

Page 44: The Pediatric Sleep Disorders

Castellanos 2016

To Summarize….

Page 45: The Pediatric Sleep Disorders

Castellanos 2016

Don’t prescribe medication to treat childhood insomnia, which usually arises from parent-child interactions and responds to behavioral intervention.

No medications are approved by the FDA for the treatment of pediatric insomnia.

TakeAway

Pointsfor the

Prescriber

Page 46: The Pediatric Sleep Disorders

Castellanos 2016

There is insufficient evidence on dosage, safety profiles and efficacy about the use of hypnotics for handling pediatric insomnia.

The few studies published about the efficacy of using pharmacological treatment versus placebo show some results with statistically significant effects, but the clinical effectiveness is not clear.

TakeAway

Pointsfor the

Prescriber

Page 47: The Pediatric Sleep Disorders

Castellanos 2016

Pharmacotherapy should only be considered for short-term use if:

Insomnia results in significant impairments in child and/or caregiver daytime functioning.

Behavioral interventions alone are ineffective OR caregivers unable to implement.

TakeAway

Pointsfor the

Prescriber

Page 48: The Pediatric Sleep Disorders

Castellanos 2016

Pharmacotherapy with behavioral treatment may be appropriate for:

Short-term crisis intervention.

Insomnia with comorbid high risk psychiatric (ADHD, MDD) or neurodevelopmental conditions (ASD).

Insomnia exacerbates psychiatric, medical conditions.

TakeAway

Pointsfor the

Prescriber

Page 49: The Pediatric Sleep Disorders

Castellanos 2016

TakeAway

Pointsfor the

Prescriber

Begin with…

Comprehensive Assessment

Initial Treatment Plan- behavioral

Page 50: The Pediatric Sleep Disorders

Castellanos 2016

TakeAway

Pointsfor the

Prescriber

If medications are still indicated…

Melatonin

Clonidine (off label); Diphenhydramine

Limited evidence. May be used with caution (all off label)-Mirtazapine; Trazodone; Benzodiazepines; Amitriptyline

NOTE: Use of antipsychotic medications for insomnia is NOT recommended.

Page 51: The Pediatric Sleep Disorders

Castellanos 2016

Medications for Pediatric Sleep Disturbances

Medication Starting Dose Titration Discontinuation

Melatonin 1-3 mg q hs Up to 9/10 mg daily

As clinically appropriate

Clonidine 0.05 mg q hs/1 week

0.05 mg/ week 0.05 mg/3 days

Diphenhydramine 12.5-25 mg q hs If necessary, based on

response and body weight

As clinicallyappropriate

Mirtazapine 3.75 mg q hs/1 week

3.75 mg/ week 7.5 mg/ 3 days

Trazodone* 25 mg q hs/1 week

25 mg/ week 25-50 mg/3 days

*Note. Continue titration until symptoms are adequately controlled, treatment-limiting side effects emerge or max daily dose is reached.

Page 52: The Pediatric Sleep Disorders

Parting Thoughts

Children are our future

We all share a responsibility for their welfare

Castellanos 2016

Page 53: The Pediatric Sleep Disorders

Castellanos 2016

Appendix.

Normal Sleep

PhasesComprehensive

Assessment &

Non-pharmacologic management

Page 54: The Pediatric Sleep Disorders

Castellanos 2016

I. Normal

Sleep Phases

Page 55: The Pediatric Sleep Disorders

Castellanos 2016

Normal Sleep

PhasesNewborns (0-3 months)

Sleep during the early months occurs around the clock and the sleep-wake cycle interacts with the need to be fed, changed and nurtured.

Newborns sleep a total of 10.5 to 18 hours a day on an irregular schedule with periods of one to three hours spent awake.

The sleep period may last a few minutes to several hours.

Page 56: The Pediatric Sleep Disorders

Castellanos 2016

Normal Sleep

PhasesInfants (4-11 months)

6 months of age, nighttime feedings are usually not necessary and many infants sleep through the night

70-80 % will do so by 9 months of age.

Typically sleep 9-12 hours during the night and take 30” to 2-hour naps, one to four times a day – fewer as they reach age one.

When infants are put to bed drowsy but not asleep, they are more likely to become "self- soothers" which enables them to fall asleep independently at bedtime and put themselves back to sleep during the night.

Those who have become accustomed to parental assistance at bedtime often become "signalers" and cry for their parents to help them return to sleep during the night.

Page 57: The Pediatric Sleep Disorders

Castellanos 2016

Normal Sleep

PhasesToddlers (1-2 years)

Need about 11-14 hours of sleep in a 24-hour period.

When they reach about 18 months of age their naptimes will decrease to once a day lasting about 1 – 3 hours.

Naps should not occur too close to bedtime as they may delay sleep at night.

Many toddlers experience sleep problems including resisting going to bed and nighttime awakenings.

Nighttime fears and nightmares are also common

Page 58: The Pediatric Sleep Disorders

Castellanos 2016

Normal Sleep

PhasesPreschoolers (3-5 years)

Typically sleep 11-13 hours each night and most do not nap after five years of age.

As with toddlers, difficulty falling asleep and waking up during the night are common.

With further development of imagination, preschoolers commonly experience nighttime fears and nightmares.

In addition, sleepwalking and sleep terrors peak during preschool years.

Page 59: The Pediatric Sleep Disorders

Castellanos 2016

Normal Sleep

PhasesSchool-aged Children (6-12 years)

Children aged six to 13 need 9-11 hours of sleep.

Usually increasing demand on their time from school (eg, HW), sports and other extracurricular/social activities.

Become more interested in TV, computers, the media and internet as well as caffeine products – all of which can lead to difficulty falling asleep, nightmares and disruptions to their sleep.

In particular, watching TV close to bedtime has been associated with bedtime resistance, difficulty falling asleep, anxiety around sleep and sleeping fewer hours.

Sleep problems and disorders are prevalent at this age

Page 60: The Pediatric Sleep Disorders

Castellanos 2016

Normal Sleep

PhasesAdolescents (13 + years)

Circadian rhythm changes means it’s normal for teenagers to want to go to bed later at night – often around 11 pm or later – then get up later in the morning.

Biological sleep patterns shift toward later times for both sleeping and waking during adolescence -- meaning it is natural to not be able to fall asleep before 11:00 pm.

Teens need about 8 to 10 hours of sleep each night to function best.

Teens tend to have irregular sleep patterns across the week — they typically stay up late and sleep in late on the weekends, which can affect their biological clocks and hurt the quality of their sleep.

Most teens do not get enough sleep…. About 85-90% of adolescents don’t get the recommended amount of sleep on school nights.

Page 61: The Pediatric Sleep Disorders

Castellanos 2016

II. Comprehensive

Assessment

Page 62: The Pediatric Sleep Disorders

Castellanos 2016

Comprehensive assessment

Primary sleep disorders (OSA, RLS, circadian rhythm disorders)

Medical, psychiatric and neurodevelopmental co-morbidities (particularly ADHD, depression & ASD

Concomitant medications, especially psychotherapeutic medications (eg, stimulants)

Comprehensive Assessment

Page 63: The Pediatric Sleep Disorders

Castellanos 2016

Comprehensive assessment…

Exacerbation primary sleep disorders

Assessment of proper sleep hygiene (e.g., electronic use, caffeine, napping)

Caregiver role

Presentation: sleep onset/maintenance

Insomnia

Page 64: The Pediatric Sleep Disorders

Castellanos 2016

III. Non-pharmacologic

management of

pediatric sleep

issues

Page 65: The Pediatric Sleep Disorders

Castellanos 2016

Behavioral interventions

Caregiver-based for younger children

Sleep training, bedtime fading, bedtime pass

CBT-I for older children and adolescents

Stimulus control, sleep restriction

Healthy sleep practices for all

Regular sleep schedule, avoidance nighttime screens, limit caffeine, age-appropriate napping.

Insomnia

Page 66: The Pediatric Sleep Disorders

Castellanos 2016

Toddlers (1-2 yo)

Maintain a daily sleep schedule and consistent bedtime routine.

Make the bedroom environment the same every night and throughout the night.

Set limits that are consistent, communicated and enforced.

Encourage use of a security object such as a blanket or stuffed animal.

Page 67: The Pediatric Sleep Disorders

Castellanos 2016

Infants (< 1 yo)

Develop regular daytime and bedtime schedules.

Create a consistent and enjoyable bedtime routine .

Establish a regular "sleep friendly" environment.

Encourage baby to fall asleep independently.

Page 68: The Pediatric Sleep Disorders

Castellanos 2016

Pre-School Children

(3-5 yo)

Maintain a regular and consistent sleep schedule.

Relaxing bedtime routine that ends in the room where the child sleeps.

Child should sleep in the same sleeping environment every night, in a room that is cool, quiet and dark – and without a TV.

Page 69: The Pediatric Sleep Disorders

Castellanos 2016

School Aged

Children (6-12 yo)

Teach parents & school-aged children about healthy sleep habits.

Continue to emphasize need for regular and consistent sleep schedule and bedtime routine.

Make child's bedroom conducive to sleep – dark, cool and quiet.

Keep TV and computers out of the bedroom.

Avoid caffeine.

Page 70: The Pediatric Sleep Disorders

Castellanos 2016

Adolescents

Make sleep a priority. Keep a sleep diary to help see patterns.

Naps can help and make teens work more efficiently, if planned right. Naps that are too long or too close to bedtime can interfere regular sleep.

Bedroom - keep it cool, quiet and dark. Let in bright light in the morning to signal the body to wake up.

Avoid coffee, tea, soda/pop, chocolate, nicotine and alcohol late in the day.

Page 71: The Pediatric Sleep Disorders

Castellanos 2016

Adolescents

Establish a bed and wake-time and stick to it, coming as close as you can on the weekends. A consistent sleep schedule helps the body to get in sync with its natural patterns.

Don’t eat, drink, or exercise within a few hours of your bedtime. Don’t leave your homework for the last minute. Try to avoid the TV, computer and telephone in the hour before you go to bed. Stick to quiet, calm


Recommended