March 2012

Sleep is not simply the absence of wakefulness,

Its a complex behavioral, physiological, and

psychological stage that involves actively coordinated brain processes

 Its unknown

Sleep deprivation leads to serious physical harm and

even DEATH (in lab animals) Amount of sleep variable from person to person Ave 8hrs, children 10, elderly < 7 How much sleep do you need? Need the amount of sleep that results in optimal daytime alertness and a sense of mental efficiency and well being

 Repeated difficulty with:

Sleep initiation
Duration Consolidation

Quality
Occurs despite age-appropriate time and opportunity

for sleep Results in daytime functional impairment for the child and family

 A study of 4175 children and adolescents aged 11-17

years, 5% met criteria for chronic insomnia which increased subsequent risk for somatic health problems, psychological problems, interpersonal difficulties, and impairments in daily activities. Altered neurobehavioral functioning resulting in symptoms such as hyperactivity, inattention, learning difficulties, and impulsivity Increased stress levels in families of children who exhibit chronic sleep disturbances (1)

 Children with these types of daytime problems

Ask parents specific questions to identify main

symptoms of major pediatric sleep disorders

insomnia is a symptom and not a diagnosis and has

multiple possible precipitating etiologies and perpetuating factors Misdiagnosis may result in children suffering years of health, educational , behavioral and emotional consequences

 Assessing: sleep habits sleep hygiene bedtime routine sleep schedules the sleeping environment the severity, frequency, and duration of the presenting

sleep complaints as well as previous treatment attempts Interview bed partners Polysomnography (sleep study)

 Difficulty falling asleep within 20 minutes of going to

bed.

Insufficient Sleep Syndrome Adjustment sleep disorder Psychophysiological insomnia Sleep apnea syndromes: central and obstructive sleep apnea Obstructive Hypopneas: air flow diminishes, yet doesnt completely cease Periodic Limb Movement Disorder Parasomnias Circadian Rhythm Sleep Disorders Restless Leg Syndrome Narcolepsy

 Often result of parental difficulties in setting limits

and managing behavior Child refusing to get ready for bed Refusing to remain in bed Requiring a parent to be present at bedtime Inappropriate/ inconsistent sleep schedule Nighttime fears Restless leg syndrome

 May require parental intervention for the child to

return to sleep Inappropriate sleep onset associations- ie parental presence not happening illness, pain Periodic limb movement disorder Sleep apnea

 Excessive movements of some parts of the body or the

whole body Undesirable physical events or experiences that occur during entry into sleep, within sleep, or during arousals from sleep: sleepwalking, terrors, nightmares, enuresis sleep related groaning

 Child refusing to wake up by him/herself

Difficulty getting out of bed in the morning

Results from inadequate sleep or parental limit setting

difficulties

 Persistent tiredness and lack of energy with a tendency

to fall asleep .
Chronic sleep deprivation Sleep disorders Psychiatric disorders Neurological causes Narcolepsy: excessive daytime sleepiness with an urge

to fall asleep (in Klein-Levin syndrome)

 B= bedtime problems

E= excessive daytime sleepiness

A= awakenings during the night R= regularity of evening sleep time and morning

awakenings S= sleep related breathing problems or snoring

 Snoring Excessive daytime sleepiness Difficulty falling asleep, Roll, kick, or move around frequently in sleep Wake up frequently

Difficult to awaken
Gasp/choke/snort in sleep Stop breathing during sleep Not enough sleep at night compared with peers of the same

age Difficult temperament

22 items completed by parents 3 point scale: yes/no/dont know & a 4pt likert scale measuring inattention/hyperactivity Provides a score representing the total amount of sleep problems the child has Validated in several sleep studies Good consistency with clear cut off scores for referral

 How likely are you to doze off or fall asleep in the following

situations? Use the following scale to choose the most appropriate number for each situation: 0= would never doze 1=slight chance of dozing 2= moderate chance of dozing 3=high chance Sitting and reading Watching TV Sitting inactive in a public place Passenger in a car for an hour without a break Lying down to rest in the afternoon Sitting and talking to someone Sitting quietly after a lunch with no alcohol In a car, while stopped for a few minutes in the traffic

 Stages of sleep repeating in a cyclical fashion throughout

the night Sleep is typically entered through stage 1 Orderly progression from stage 1 through 4 within 45 minutes of falling asleep. Within 90 minutes, the first REM period has occurred
This NREM-REM pattern = sleep cycle The sleep cycle lasts approx 90 minutes and recurs

continuously throughout the night. REM sleep periods lengthen with each sleep cycle so is most prominent the last third of the night REM influenced by circadian rhythm not deprivation

 REM

NREM

Stage 1 Stage 2 stage 3 and 4

25% 75% 5% 45% 25%

 The arousal threshold is lowest for stage 1 sleep Highest for delta sleep (hence deep sleep) Variable for REM Delta sleep is the most refreshing and deprivation of this

stage often results in daytime sleepiness despite adequate length of sleep. The sense of unrefreshing sleep reported by the elderly is often related to low percentages of delta sleep. Delta sleep is most prominent in the first third of the night and virtually disappears during the last third of the night. Sleep deprivation results in longer periods of delta sleep in the beginning of the night.

 First night following total sleep deprivation, a rebound of

delta sleep is noted first. Delta sleep is recovered at the expense of other sleep stages. REM rebound occurs later during the night or on subsequent nights. Delta sleep thought related to the maintenance of important biological functions Selective deprivation of either delta or REM results in rebound of that particular portion of that sleep stage. For example REM rebound is often seen following the abrupt discontinuation of drugs that suppress REM activity such as antidepressants, and is experienced as vivid dreaming and nightmares.

 Cognitive aspects at low level during stage 1 When awakened from stage 1 experience thought fractions

or vague images When awakened from delta sleep most report no mental activity at all When awakened from REM sleep- dreams Dreaming is only one facet of a host of complex biological processes activated during REM sleep that affect almost every bodily fxn: bursts of tachycardia, penile tumenscence, peripheral skeletal muscle atonia REM- A highly active mind superimposed on a picture of a motionless paralyzed body- paradoxical sleep

 Onset of sleep characterized by reduced

responsiveness to environmental stimuli Sleep deprived car drivers tend to react sluggishly to traffic hazards and are more vulnerable to crashes. Responsiveness to important stimuli maintained die mother selectively sensitive to her babys crying. Retrograde amnesia; memory for events just prior to onset of sleep is lost You dont remember the moment of sleep onset or the events during brief awakenings during the night

 Primary snoring

Upper airway resistance syndromesnoring and

increased respiratory effort Partial obstructive hypoventilation Hypopneas Osasnoring, apneic pauses, arousals Diagnosis requires a polysomnographic recording

 Cessations in air flow through the nares or mouth lasting

10 seconds or greater Cyclic asphyxia hypoxia, hypercarbia, acidosis which can result in cardiac arrhythmias Pulmonary and systemic hypertension are evident during apneas Cardiac output falls during apneas and rise to normal levels following their termination Apneas are terminated by arousals, which are sudden generalized activations of the brain that result in transient disruption of sleep Arousals lead to a profound sleep fragmentation and poor sleep quality responsible for daytime hypersomnolence and emotional consequences of the disorder

 The pharyngeal walls collapse repetitively during sleep

causing intermittent sleep related upper airway obstruction and cessation in ventilation (apneas). Upper airway closure is thought to occur because of a failure of the upper airway dilator muscles.
Central Sleep Apnea usually coexists with OSA Cessation of ventilation is related to a concomitant

loss of inspiratory effort.

 Loud snoring, prolonged pauses in respiration during

sleep, daytime hypersomnolence, disturbed nonrefreshing sleep, weight gain Source of embarrassment placing strain on a relationship Repeated awakenings Unusual sleeping positions such as sitting or kneeling at bedside in association with severe hypoxemia Sleepwalking and nocturnal vocalizations are common GERD AM frontal HA due to episodic asphyxia and consequent cerebral vasodilation

Continuous positive airway pressure (CPAP) Dental devices that prevent mandibular collapse or tongue retrusion Nasal surgery Tracheostomy Antidepressants are REM suppressants and if apneas occur mostly during REM sleep their use can diminish the frequency of these REM related apneas Serotonergic mechanisms have been implicated in the control of respiration during sleep so the use of SSRIs may diminish apnea frequency independent of their REM affects Oxygen Weight loss Refrain from alcohol, hypnotic agents, CNS depressants as they can exacerbate OSA

 Identifies pathological processes during sleep Electroencephalogram (EEG) Electromyogram (EMG) of skeletal muscle, usually the

submentalis, also the anterior tibialis to detect periodic leg movements Electrooculogram (EOG): detects slow rolling eye movments that are present during the initial portions of stage 1 then rapid eye movements in REM Monitors for airflow at the nose and mouth Respiratory effort strain gauges placed around chest and abdomen Noninvasive oxygen saturation monitors Audiovisual monitoring of gross body movements

 Behavioral interventions should be the mainstay of

treatment of pediatric insomnia and should be offered as initial treatment : Extinction Scheduled awakenings Positive bedtime routines
Medication should rarely be the first treatment choice Medications should not be used as a stand-alone

therapy

 No caffeine Limit etoh close to bed (2h per drink) Restrict sleep time to 6-8 hours, with set wake time every day of

the week no naps Before sleep may engage in tiring activity like reading or watching TV- in bed fine because you wake-up more if get up Tell patients its not OK to ruminate. Counteract rumination with: mental distraction; visualization; recitals of prayers/poems etc.; count breath to 10 and start over. If brain too busy go back to tiring activity such as reading or TV do this in 20m increments

 Review sleep hygiene education with parent and child

Address environmental factors: noise, temperature,

light Sleep practices: bedtime routines, sleep-wake schedule Diet: timing of meals, caffeine These general principles are paramount to the successful treatment of childhood insomnia as part of the primary intervention and as an adjunct to pharmacotherapy.

 Failure of the child to adequately respond to

behavioral interventions Inability to implement planned behavioral intervention owing to a lack of physical or emotional resources ( parent occupation, financial and housing difficulties, parental psychopathology).

 Duration of action: a short half-life for sleep onset

problems. Longer acting medication for sleep maintenance issues- realizing daytime hangover more likely.
Dosing and timing of administration: kids metabolize

some hypnotics faster so be underdosed leading to disinhibition rather than sedation, resulting in agitation.

 A potential exists for drug-drug interactions with:

Concurrent medications Alcohol/illicit substances Herbal remedies (interactions largely unknown)

Medical problems so as not to exacerbate illness Limited or no opportunity for adequate follow-up and

monitoring of side effects.

 Insomnia occurring in the context of a primary sleep

disorder (OSA) Insomnia symptoms resulting from inappropriate expectations regarding a developmentally normal childs sleep behaviors (putting a child to bed too early). Pregnancy A history of impulsive and non-accidental overdoses, given that some hypnotics (ie, benzodiazepines) have a high potential for toxicity in overdose.

 There is a lack of FDA approved medications for use as

hypnotics in children. Insomnia therapy in children very controversial

you will likely not get the same opinion from any two

sleep physicians Dr. Ameet Daftary I can testify that there definitely is no standard to prescribing meds for pediatric insomnia . Dr. Deoras

 Clinicians working in pediatric and child psychiatric

settings must also be educated in regard to the recognition, diagnosis, and treatment of sleep disorders in children and adolescents, with training programs having a major role in improving knowledge of pediatric sleep medicine practices. pediatric clinical trials to assess efficacy, safety, and tolerability evidence-based pharmacologic guidelines may then be developed to help guide pharmacotherapy approaches in children with insomnia, especially in children with developmental and psychiatric disorders.

 Drugs FDA approved for insomnia in children/adolescents: There is little known about pharmacologic therapy for treating

insomnia in children. 2 products are FDA-approved for use in older children:

1) Diphenhydramine, specifically Unisom Sleepmelts, may be used in children 12 years of age and older. The labeled dose is 50 mg by mouth at bedtime. 2) Flurazepam is labeled for insomnia in children 15 years or older at a dose of 15 mg by mouth at bedtime. This product is not recommended for use in patients under the age of 15 years. Flurazepam is a benzodiazepine that itself has a short half-life (2.3 hours), but its active metabolite has an extremely long halflife (74-90 hours) which may make this agent difficult to use for insomnia since the effects may persist so long.

 Lavender when used as an aromatherapy agent ( a few

drops of oil on the pillow at bedtime) may reduce nighttime arousals and avoid dependence on sedating drugs, although no systematic assessment of this practice has been conducted in children.

 the treatment of pediatric insomnia needs to be diagnostically driven (ie, determined by the specific sleep diagnosis). For example,

the etiology of sleep onset delay and bedtime resistance in children with attentiondeficit hyperactivity disorder (ADHD) appears to be multifactorial in nature, with potential causes that include, but are not limited to, direct or rebound effects of psychostimulants and psychiatric comorbidities such as oppositional defiant disorder and anxiety disorders. Other potential causes of bedtime settling difficulties in these children include sensory integration deficits, abnormal arousal regulation, and

 No randomized clinical trials of alpha agonists

specifically for the treatment of pediatric insomnia have been conducted, although a large study of clonidine for the treatment of ADHD in children confirmed that sedation was the most common side effect, and that this appeared to diminish over time. A case series reported the beneficial and fairly tolerable profile of clonidine in intractable sleep problems in children and young adults with neurodevelopmental disorders. (3)

 Clonidine (Catapres) and guanfacine (Tenex) are

noradrenergic alpha-2 agonists that are widely used in pediatric and psychiatric practice.
Clonidine is often prescribed to target sleep onset

delay in children with ADHD resulting from an settling problem or stimulant rebound at bedtime.

 Less sedating and demonstrates lesser anticholinergic

and cardiovascular side effects when compared with clonidine owing to its more selective alpha-receptor binding. Guanfacine may theoretically be helpful in children with an underlying seizure disorder, given that guanfacine can have anticonvulsant effects on seizure susceptibility, whereas clonidine exhibits proconvulsant effects.

 generally recommended that clonidine should be initiated as a bedtime dose of 0.05 mg and gradually titrated by 0.05 mg every 3 to 5 days based on

tolerability and efficacy. Guanfacine is typically initiated as a bedtime dose of 0.5 mg with gradual titration by 0.5 mg every 4 to 5 days. Effects of clonidine on sleep architecture appear minimal, but REM suppression may occur, resulting in REM rebound upon discontinuation. Other potential side effects include anticholinergic effects, irritability, and dysphoria, and rebound hypertension upon abrupt discontinuation. Clonidine has a narrow therapeutic index and has been associated with significant cardiotoxicity and death in overdose.

 primarily synthesized by the pineal gland, and its

secretion is regulated by the suprachiasmatic nucleus in the hypothalamus. Given the high levels of endogenous melatonin secretion during the night (associated with nocturnal sleepiness) and the low levels during the day (associated with daytime wakefulness), it is believed that the circadian pattern of melatonin secretion is one of the primary mechanisms by which sleep-wake cycles are controlled

 (hypnotic) properties; therefore, it has been used in the treatment of circadian rhythm disorders (eg, delayed sleep

phase disorder, shift work disorder) and primary insomnia.38 The half-life of melatonin is 40 minutes, with Exogenous melatonin at a dose of 0.3 mg appears to produce blood levels that are equal to physiologic nocturnal levels, has a rapid sedating effect, and reduces sleep onset latency and latency to stage 2 sleep with minimal effects on REM sleep architecture.39

 well tolerated and effective in reducing sleep onset latency

and bedtime settling difficulties and improving total sleep time but had little effect on nighttime awakenings.53 Furthermore, disappointing regarding improvements in daytime functioning in these studies (ie, behavior, cognitive performance, and quality of life).47,48 Melatonin also appears to have proinflammatory properties and should be used with caution in children receiving corticosteroids and children with asthma.57

 effective in reducing sleep onset delay and increasing sleep

maintenance and total sleep time at doses ranging from 0.5 to 10 mg in

children syndrome,42 Rett syndrome,43 and Angelmans syndrome,44 and in individuals with blindness.45 Melatonin also appears to be effective and well tolerated in the treatment of insomnia in children with ADHD4648 and in children with autism spectrum disorders.4951 The studies. Typical dose ranges are 1 mg in infants, 2.5 to 3 mg in older children, 5 mg in adolescents, and 0.5 to 10 mg in children with special needs, irrespective of age.50 Although

 A case study of two youths with autistic disorder and insomnia reported effi cacy of ramelteon in the treatment of insomnia.59 Tasimelteon is another

novel hypnotic in the developmental pipeline that appears to have more balanced agonist activity at M1 and M2 receptors. Agomelatine, currently in developmental phase, appears to have advantages in treating sleep disorders in depression and anxiety
Owens & Moturi disorders due to its dual action properties (MT-1 and MT-2 receptor agonist as

well as 5-HT2C antagonist).

 Prescription and OTC antihistamines are the most

commonly used sedatives in pediatric practice.30 Agents such as diphenhydramine appear to be a more acceptable choice for insomnia owing to parental and provider familiarity. group. Both diphenhydramine and hydroxyzine appear to exert their sedative effects through H1-receptor blocking properties, with minimal effects on sleep architecture. They are

 preoperative sedating agents. A recently published

study that examined the effectiveness of diphenhydramine in treating sleep problems in infants concluded that diphenhydramine was no more effective than placebo in reducing nighttime awakening or improving overall parental satisfaction with sleep.60 Tolerance to antihistamines can develop, often necessitating increasing doses and a resultant increase in side effects.61

 Side effects due to antihistamines related to

anticholinergic, alpha-adrenergic, histaminergic, and dopaminergic effects include daytime drowsiness, dry mouth, urinary retention, hypotension, tinnitus, dizziness, and weight gain. Rare instances of cardiac arrhythmias, respiratory disturbances, rhabdomyolysis, acute renal failure, and seizures have also been reported in overdoses.

 Many OTC cold and allergy preparations contain first-generation antihistamines

(diphenhydramine and doxylamine); therefore, parents should be alerted to the possibility of accidentally overdosing a child by giving multiple doses of such OTC medications.63 Caution should be exercised in prescribing diphenhydramine in adolescents with a known history of illicit substance dependence, because anxiolytic and anticholinergic properties of antihistamines can become popular alternatives to cannabis and other street drugs in this population. The sedative properties of antihistamines are often potentiated by concurrent use of alcohol, antidepressants, anxiolytics, and antipsychotics.

 barbiturates and chloral hydrate are sometimes used

as hypnotics in children. Barbiturates have a narrow therapeutic index, carry a high risk for dependency, and have the potential to cause respiratory depression; their use should be avoided in children. REM rebound with nightmares and withdrawal insomnia can occur during discontinuation.

 Patient interview: HPI, sleep/wake habit history, sleep

hygiene history: meal/exercise times, ambient noise, light, temperature, etc. Pattern of consumption of recreational substances (especially caffeine and alcohol) and medications, general medical/psychiatric/surgical history Sleep diary Inventories of daytime sleepiness/alertness Psychological inventories Bed partner interview Physical and mental status examination Serum laboratory tests Polysomnography

 Chloral hydrate is a commonly prescribed sedative hypnotic in children and is often used at low doses (2550

mg/kg/dose), with higher doses up to 100 mg/kg in children less than 5 years old showing good demonstrable
Pharmacologic Treatment of Pediatric Insomnia efficacy and tolerability.64 Both of these medications are rarely

indicated for insomnia at this time given their significant side effect profile, and the American Academy of Pediatrics in 1993 recommended the use of chloral hydrate in children for short term sedation only owing to the risk of hepatotoxicity.

 receptors. This class of drugs typically reduces sleep onset latency and improves initiation and

maintenance of non-REM sleep; most suppress slow-wave sleep. These medications have anxiolytic, muscle relaxant, and anticonvulsant properties and have primarily been used for insomnia in adults. The shorter onset of action of some benzodiazepines is useful for treating sleep onset insomnia. Although agents with a longer half-life and duration of action may help with sleep maintenance, they are also more likely to cause impaired daytime functioning owing to morning grogginess and daytime sleepiness. This class

 This class of medica-

tion is used for short-term or transient insomnia,

especially when coexisting clinical conditions (such as anxiety) warrant their use. Benzodiazepines such as clonazepam have also been shown to be useful in treatment for periodic limb movement disorder and as a primary treatment for severe partial arousal parasomnias (ie, sleep walking, sleep terrors) owing to their suppression of slow-wave sleep and increase in arousal threshold.

 Potential side effects of benzodiazepine use include

behavioral disinhibition and agitation characterized by aggression and impulsivity and memory impairments (anterograde amnesia). Given the risk of habituation and addiction with these medications, as well as the potential for withdrawal symptoms on discontinuation, benzodiazepines have limited use in children and adolescents. Due to their muscle relaxant properties, benzodiazepines should be avoided in suspected sleep-disordered breathing such as obstructive sleep apnea.

 This class of medications includes selective benzodiazepine

receptor agonists (BZRAs) (different chemical structure compared with traditional benzodiazepines, with preferential binding affinity to GABA-A receptor containing alpha-1 subunits),65 such as zaleplon (Sonata), zolpidem (Ambien), and eszopiclone (Lunesta), as well as nonselective BZRAs (share molecular structure with benzodiazepines, with affinity to one or more subtypes of benzodiazepine receptors), such as estazolam, flurazepam, quazepam, temazepam, and triazolam.

ultra-short half-life (zaleplon, 12 hours), short half-life (zolpidem, 23 hours), and intermediate-to-long half-life (eszopiclone, 57 hours). Selective BZRAs such as zolpidem and zaleplon appear to be most useful in improving sleep initiation. A recent study in adults with insomnia concluded that zaleplon may also be an appropriate treatment for use when patients awaken during the night and have difficulty reinitiating sleep.66 Eszopiclone and extended release zolpidem (Ambien CR) have a longer elimination half-life and may be useful in sleep maintenance. Due to lack of development of tolerance at 6 months shown in adult studies,67 eszopiclone has been approved for longer-term use. None of these medications are approved by the FDA for use in children; therefore, the use of these medications in children and adolescents should be considered off-label.

Reported side effects of BZRAs in the pediatric population include zaleplon-induced sleep walking in an adolescent68 and drowsiness, ataxia, dizziness, confusion, and blurred speech in a nonaccidental overdose of zaleplon in a 15-year-old adolescent.69 Central nervous symptoms but no fatalities were reported in a case series of 12 accidental zolpidem overdoses in children aged 20 months to 5 years and five nonaccidental Owens & Moturi overdoses in adolescents aged 15 to 16 years.70 Recent reports on the potential of zolpidem to induce complex sleep-related behaviors such as sleep eating, sleep walking, and sleep driving in adults raise additional concerns about its use in children. Side effects of eszopiclone include an unpleasant metallic taste and headaches; abrupt withdrawal after prolonged use (>2 weeks) may cause rebound insomnia. BZRAs are contraindicated in insomnia associated with sleep-disordered breathing because they blunt the arousal response to the hypoxemia and can worsen apnea.

 antidepressants with sedating properties have

been used to treat insomnia in children, especially in

child psychiatry populations, for a number of years. A few randomized controlled and open label trials of antidepressants such as trazodone, trimipramine, doxepin, paroxetine, and nefazodone have been conducted in adults with insomnia. Trazodone, trimipramine, and doxepin have been shown to have modest efficacy in shortterm treatment of insomnia.7175

 Trazodone is a serotonin (5-HT2) receptor antagonist

that promotes sleep by inhibiting uptake of serotonin and blocking histamine receptors. Sedative-hypnotic properties of trazodone occur only at lower doses (2550 mg/d), whereas higher doses appear to have antidepressant properties. Priapism is an infrequent but potentially serious side effect.

 SSRIs fluvoxamine and citalopram, have also been used to

treat insomnia, particularly in the setting of comorbid mood or anxiety disorders. Although trazodone can cause REM suppression and increases in slow-wave sleep, SSRIs suppress REM sleep, prolong REM onset, and increase the number of rapid eye movements (REM density), which results in a characteristic polysomnographic finding (prozac eyes). SSRIs may exacerbate symptoms of restless legs syndrome and periodic limb movements in sleep.

 tricyclic antidepressants such as trimipramine, amitriptyline, and dox epin appear to be the most sedating among tricyclic antidepressants

(ie, have potential use in sleep onset and sleep maintenance insomnia), insomnia. Most tricyclics are potent REM suppressants and tend to suppress slowwave sleep. Tricyclics should be used at the lowest possible doses, and caution should be exercised due to their anticholinergic properties and treatment-emergent anxiety and agitation. Tricyclics also tend to exacerbate symptoms of restless legs syndrome. The potential for significant cardiotoxicity in overdose should be considered when using tricyclics in patients with a risk of suicidal ideation.

 Another sedating antidepressant, mirtazapine, acts as a histamine (H1) receptor antagonist, and both reduce sleep onset latency and increase sleep

duration with little or no effects on REM sleep. Both trazodone and mirtazapine may result in significant daytime sedation. The use of antidepressants for a mood disorder with associated sleep difficulties depends on the type of sleep problem (insomnia versus hypersomnia versus comorbid primary sleep disorder) and the severity of underlying mood symptoms. Often, sleep difficulties improve with treatment of the underlying mood disorder, and, conversely, treating sleep problems or an underlying primary sleep disorder can improve mood-disordered symptoms.

 Owing to the limited data on the safety and tolerability of

the use of antipsychotics and other mood stabilizers in children with insomnia, these medications should be used with extreme caution as primary agents to treat insomnia. Furthermore, many of the atypical antipsychotics and antiepileptic drugs cause weight gain, which may exacerbate an underlying primary sleep disorder such as obstructive sleep apnea. Abrupt discontinuation of these medications can result in REM rebound.

 Chronic medical conditions in children such as asthma,

atopic dermatitis, juvenile rheumatoid arthritis, migraine headaches, inflammatory bowel disease, diabetes, sickle cell disease, epilepsy, and renal disease have been associated with an increased risk of sleep problems. careful consideration of whether pharmacologic treatment of insomnia could potentially exacerbate underlying medical illness, or whether it will improve the overall quality of life.

 Nasal obstruction Large uvula Low-lying soft palate Retrognathia, micrognathia, other craniofacial abnormalities Excessive and redundant pharyngeal tissue Pharyngeal masses such as tumors or cysts Macroglossia Tonsilar hypertrophy Vocal cord paralysis

Obesity
Hypothyroidism acromegaly

 Awake: pattern of low voltage with mixed frequencies Drowsiness: rhythmic alpha activity (8-12 cps) Stage 1: disappearance of rhythmic alpha and low voltage

and mixed frequency pattern (3-7 cps) Stage 2: sleep spindles (12-14 cps) and K complexes (negative sharp waves followed by slower positive waves. Stage 3 and 4: are collectively called delta sleep/ deep sleep/ slow wave sleep, showing high-amplitude slow delta activity (<2cps) REM: lowest-voltage mixed frequencies showing skeletal muscle atonia via active CNS inhibition

 Sleep quality refers to the integrity of the sleep

architectural pattern. Impairments in sleep quality appear polysomnographically as an increase in the number of arousals (brief awakenings and stage changes), awakenings, and body movements; an increase in the shallow stages of sleep (1 and 2) a decrease in deep (delta)sleep; and a decrease in the number of wellformed sleep cycles

 Any medication prescribed for sleep-related difficulties in children

should be monitored closely for the emergence of side effects. Given the paucity of data on the safety and efficacy of these medications in children, caution should be exercised as with any pediatric off-label medication use. Some of these medications can precipitate or exacerbate additional problems such as daytime sleepiness, confusional arousals, sleep walking, and nightmares (eg, alpha agonists such as clonidine have rapid eye movement [REM]-suppressing properties and can precipitate increased nightmares due to REM rebound if withdrawn abruptly).

 Medication may also be considered to treat insomnia

within the context of medical illness ( hospitalization, chronic pain)

or in self-limited situations such as travel or an acute

stressor (ie, death in the family).

 Despite the absence of Food and Drug Administration

(FDA)-approved medications for use as hypnotics in children, several studies have indicated that a variety of over-the-counter preparations (OTC) and prescription medications are being prescribed for childhood insomnia in inpatient and outpatient clinical settings; therefore, the clinician should have a basic understanding of general principles of pharmacologic treatment of pediatric insomnia and familiarity with pharmacologic properties of the most commonly used drugs.

 Hypnotic medications with specific properties should

be avoided if insomnia occurs in the presence of an underlying untreated primary sleep disorder. For example, medications with respiratory depressant properties (eg, chloral hydrate, benzodiazepines) can be dangerous in the presence of comorbid obstructive sleep apnea, and sedating serotonin reuptake inhibitors (SSRIs) may exacerbate the symptoms of restless legs syndrome.

 Antipsychotics and Antiepileptic Drugs

Antipsychotics and antiepileptic drugs (AEDs) are prescribed in children and

young adults with comorbid psychiatric disorders and sleep disturbances, primarily for their
Pharmacologic Treatment of Pediatric Insomnia
mood-stabilizing properties. AEDs are also used for treatment of comorbid

epilepsy. In adult studies, antipsychotics such as olanzapine and risperidone have been shown to increase sleep stage 2 and delta sleep and suppress REM sleep, whereas quetiapine appears to have lesser REM suppressant effects.76,77

lesser REM suppressant effects.76,77 Some antiepileptic drugs may also reduce the amount of sleep fragmentation and can lead to stabilization of sleep,78 whereas others such as phenytoin and carbamazepine increase slow-wave sleep and reduce stage 1 and 2 NREM sleep. Lamotrigine increases total REM sleep with fewer sleep stage shifts, and treatment with felbamate has been associated with insomnia in 9% of individuals.79 Although there are no systematic studies to date assessing the effectiveness of these medications to treat pediatric insomnia, one open label naturalistic study of risperidone for the treatment of disruptive behaviors in children with special needs showed that sleep quality improved in 88% of subjects with preexisting sleep disturbance.80

 adults, these products remain largely untested in the pedi atric population with regard to efficacy and safety. Studies in adults have

shown some evidence of the efficacy of valerian root when compared with benzodiazepines in treating insomnia,81 and some empiric data for the use of hops as a sedative also exist. A recent American Academy of Sleep Medicine clinical practice review concluded that herbal preparations containing lemon balm, chamomile, and passion flower have limited to no evidence of efficacy, and suggested that kava-kava and tryptophan are associated with significant safety concerns (necrotizing hepatitis and eosinophilic myalgia syndrome, respectively).82 Herbal

 Children with specific genetic and neurodevelopmental syndromes such as

autism, Angelmans syndrome, Rett syndrome, Williams syndrome, and SmithMagenis syndrome are more susceptible to sleep problems. These problems are often more severe, of longer duration, and more challenging to treat owing to several factors (eg, cognitive delays, comorbid seizures, pain, hyperactivity).29 Management of sleep disturbances in this population must include an assessment for the presence of these confounding factors (eg, nocturnal seizures causing nighttime arousals, bedtime resistance associated with self-injurious behavior), because behavioral and pharmacologic treatment must be appropriately tailored to these conditions.

 in children with anxiety

and mood disorders, treatment of underlying anxiety

or mood symptoms with antide pressants and anxiolytics can be helpful in alleviating sleep difficulties. Although cognitive behavioral strategies should be considered as both first-line and long term treatment for sleep difficulties in children with psychiatric disorders,