Pediatric Sleep Pharmacology

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Overview of pediatric sleep disorders

This article reviews common sleep disorders in children and pharmacologic options for them. Discussions of pediatric sleep pharmacology typically focus on treatment of insomnia.1, 2, 3 Although insomnia is a major concern in this population, there are other conditions that warrant review. Narcolepsy, parasomnias, restless legs syndrome (RLS), and sleep apnea are also discussed here.

Sleep Development in Youth

Although the need for sleep is biologic, the way people sleep is learned. Children learn how to sleep or form associations with sleep based on their families. As the child is readied for bed, the child may associate sleep onset with particular events. If the child associates parental attention or activity with sleep, any awakenings during the night may then necessitate parental attention. If returning the child to sleep requires frequent parental assistance, the parents’ sleep is disturbed and

Insomnia

Insomnia is characterized in adults by difficulty falling asleep and/or staying asleep, with associated subjective daytime impairment. In children, it is the parent who leads the family to seek medical attention. The young child may awaken for any number of reasons and eventually falls asleep again; however, the parent’s sleep schedule is disrupted. The medical history is incomplete without a discussion of what the parents’ sleep was like before they were parents. If the parents had any prior

Chloral Hydrate

Chloral hydrate (CH) is a commonly used sedative hypnotic, and it is often prescribed to both children and adults. It causes drowsiness and sedation, then sleep within 1 hour. The plasma half-life is 8 to 12 hours in older children and adults, but for neonates and infants is 3 to 4 times longer.20 Usual doses ranges between 25 and 50 mg/kg/dose up to a maximum of 1 g per dose by mouth or as needed. Higher doses, 80 to 100 mg/kg, have been given to children younger than 5 years with good effect

Clonidine

Clonidine was originally marketed for the treatment of hypertension under the trade name Catapres, but its sedating properties have led to its use as a soporific. No randomized trials of clonidine specifically for children with insomnia were found. Clonidine is a central α2-adrenergic receptor agonist, with a half-life of 6 to 24 hours. Onset of action is within 1 hour, and its peak effects are at 2 to 4 hours. At least 50% is excreted unchanged in the urine. Side effects include hypotension,

Off-label use of prescription hypnotics

Prescription hypnotics do not have an FDA indication for adolescents younger than 18 years. An off-label use as an adjunct to the behavioral modification of the circadian problem may be considered in certain clinical situations. Because these patients typically only have sleep-onset insomnia without significant nocturnal disruption, a short-acting hypnotic agent may be considered for a short period of time. Zaleplon, a nonbenzodiazepine hypnotic, may theoretically be used in adolescents with

Off-label use of neuroleptics

Neuroleptics such as risperidone, quetiapine, aripiprazole, and olanzapine are typically prescribed to treated psychiatric conditions. Their off-label use in children with psychiatric or developmental disorders has been reported.46, 47, 48, 49 Neuroleptics are also used off-label to treat insomnia in adults.50, 51, 52 Given this situation, it is tempting to consider the use of neuroleptics in the treatment of sleep disorders such as insomnia in children. However, there are no published data on

Narcolepsy in children and adolescents

Narcolepsy is a neurologic syndrome characterized by excessive daytime sleepiness that is typically associated with cataplexy, sleep paralysis, and hypnagogic hallucinations. Patients often have disturbed nocturnal sleep and pathologic manifestations related to rapid REM sleep. Age at onset varies from childhood to the fifth decade, with a peak in adolescents and young adults.53 The first symptoms often develop at approximately the time of puberty. Although the cause is not clear, narcolepsy

Parasomnia treatment in children

There are no medications with an FDA indication in children for any of the different parasomnias listed in the ICSD.84, 119 This article discusses off-label use of pharmacotherapies for parasomnias in youth.

Summary

There is a need for more information on the pharmacologic management of sleep disorders in children. Pharmacologic guidelines need to be developed specifically for sleep disorders in children. These guidelines should be FDA approved for the specific sleep disorder and pediatric age group. Easy-to-swallow, chewable, or liquid forms of these medications are needed. Integration of behavioral and pharmacologic treatments may yield better patient outcomes, and would require psychiatrists and other

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References (125)

  • B.R. Kornum et al.

    Narcolepsy with hypocretin/orexin deficiency, infections and autoimmunity of the brain

    Curr Opin Neurobiol

    (2011)
  • A. Ivanenko et al.

    Modafinil in the treatment of excessive daytime sleepiness in children

    Sleep Med

    (2003)
  • S.B. Yeh et al.

    Efficacy of modafinil in 10 Taiwanese patients with narcolepsy: findings using the multiple sleep latency test and Epworth Sleepiness Scale

    Kaohsiung J Med Sci

    (2010)
  • J.L. Carroll

    Obstructive sleep-disordered breathing in children: new controversies, new directions

    Clin Chest Med

    (2003)
  • C.L. Marcus et al.

    Use of nasal continuous positive airway pressure as treatment of childhood obstructive sleep apnea

    J Pediatr

    (1995)
  • D.L. Picchietti et al.

    Early manifestations of restless legs syndrome in childhood and adolescence

    Sleep Med

    (2008)
  • I. Mohri et al.

    Restless legs syndrome (RLS): an unrecognized cause for bedtime problems and insomnia in children

    Sleep Med

    (2008)
  • D. Picchietti

    Is iron deficiency an underlying cause of pediatric restless legs syndrome and of attention-deficit/hyperactivity disorder?

    Sleep Med

    (2007)
  • S.J. England et al.

    l-Dopa improves restless legs syndrome and periodic limb movements in sleep but not attention-deficit-hyperactivity disorder in a double-blind trial in children

    Sleep Med

    (2011)
  • A.S. Walters et al.

    Dopaminergic therapy in children with restless legs/periodic limb movements in sleep and ADHD. Dopaminergic Therapy Study Group

    Pediatr Neurol

    (2000)
  • R.P. Allen et al.

    Clinical efficacy of ropinirole for restless legs syndrome is not affected by age at symptom onset

    Sleep Med

    (2008)
  • S. Quilici et al.

    Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome

    Sleep Med

    (2008)
  • M.L. Alonso Alvarez et al.

    Arch Bronconeumol

    (2008)
  • C.J. Schnoes et al.

    Pediatric prescribing practices for clonidine and other pharmacologic agents for children with sleep disturbance

    Clin Pediatr (Phila)

    (2006)
  • J.A. Owens et al.

    Medication use in the treatment of pediatric insomnia: results of a survey of community-based pediatricians

    Pediatrics

    (2003)
  • S.D. Stojanovski et al.

    Trends in medication prescribing for pediatric sleep difficulties in US outpatient settings

    Sleep

    (2007)
  • J.L. Blumer et al.

    Potential pharmacokinetic basis for zolpidem dosing in children with sleep difficulties

    Clin Pharmacol Ther

    (2008)
  • T.I. Morgenthaler et al.

    Practice parameters for behavioral treatment of bedtime problems and night wakings in infants and young children

    Sleep

    (2006)
  • R.C. Haydon

    Are second-generation antihistamines appropriate for most children and adults?

    Arch Otolaryngol Head Neck Surg

    (2001)
  • E.O. Meltzer

    Comparative safety of H1 antihistamines

    Ann Allergy

    (1991)
  • A.M. Baker et al.

    Fatal diphenhydramine intoxication in infants

    J Forensic Sci

    (2003)
  • J.P. Corey et al.

    Nasal congestion: a review of its etiology, evaluation, and treatment

    Ear Nose Throat J

    (2000)
  • F. Gengo et al.

    The pharmacodynamics of diphenhydramine-induced drowsiness and changes in mental performance

    Clin Pharmacol Ther

    (1989)
  • K.S. Albert et al.

    Pharmacokinetics of diphenhydramine in man

    J Pharmacokinet Biopharm

    (1975)
  • K.J. Simons et al.

    Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults, and children

    J Clin Pharmacol

    (1990)
  • D. Merenstein et al.

    The Trial of Infant Response to Diphenhydramine: the TIRED study–a randomized, controlled, patient-oriented trial

    Arch Pediatr Adolesc Med

    (2006)
  • E.K. Adam et al.

    Sleep timing and quantity in ecological and family context: a nationally representative time-diary study

    J Fam Psychol

    (2007)
  • N. Nigro et al.

    Minerva Pediatr

    (1975)
  • J. Pershad et al.

    Chloral hydrate: the good and the bad

    Pediatr Emerg Care

    (1999)
  • P.C. Zee

    Shedding light on the effectiveness of melatonin for circadian rhythm sleep disorders

    Sleep

    (2010)
  • I.M. van Geijlswijk et al.

    Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT

    Psychopharmacology

    (2010)
  • I.M. van Geijlswijk et al.

    The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis

    Sleep

    (2010)
  • J. Wagner et al.

    Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia

    Ann Pharmacother

    (1998)
  • N. Buscemi et al.

    Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis

    BMJ

    (2006)
  • J.E. Jan et al.

    Melatonin replacement therapy in a child with a pineal tumor

    J Child Neurol

    (2001)
  • M.G. Smits et al.

    Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial

    J Child Neurol

    (2001)
  • M.B. Wasdell et al.

    A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities

    J Pineal Res

    (2008)
  • J. Wirojanan et al.

    The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome

    J Clin Sleep Med

    (2009)
  • M. Hoebert et al.

    Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia

    J Pineal Res

    (2009)
  • M.W. Johnson et al.

    Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects

    Arch Gen Psychiatry

    (2006)

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