What is the role of medications in the treatment of pediatric sleep disorders?

Updated: Oct 09, 2018
  • Author: Sufen Chiu, MD, PhD; Chief Editor: Caroly Pataki, MD  more...
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Pharmacotherapy for insomnia in youth is generally not a permanent intervention. For transient episodes of insomnia, melatonin or antihistamines such as diphenhydramine (Benadryl) have been used clinically with varying degrees of success.

For patients with nocturnal enuresis, desmopressin therapy may be helpful. Individuals with primary enuresis and lack of circadian rhythmicity of plasma arginine vasopressin are more likely to respond to desmopressin therapy. This agent reduces nocturnal urine production, has better short-term results than the alarm method, is effective in 50-85% of individuals, and generally is well tolerated; recidivism after discontinuance can present a problem. Some individuals can experience severe hyponatremia and seizures, which is why the intranasal form of desmopressin has been discontinued. Treatment with desmopressin tablets should be interrupted during episodes of fluid and/or electrolyte imbalance, such as fever, recurrent vomiting or diarrhea, vigorous exercise, or other conditions associated with increased water consumption.

Imipramine therapy has been used historically in the treatment of enuresis; however, it is not a first-line medication, given its potentially serious cardiac adverse effects. This agent (given in a dose of 25-100 mg, depending on the age and size of the patient) may be effective, but there are concerns about potentially serious adverse effects, which often outweigh the benefits in patients with relatively benign problems. Baseline electrocardiography (ECG) is required, with titration and dose increases and periodic monitoring. The clinician should also monitor blood pressure, pulse rate, and review cardiovascular issues at each visit.

For patients with PLMS or RLS, dopaminergic therapy may be necessary; however, only limited data on dopaminergic therapy in youths are available. Pergolide (withdrawn from the US market on March 29, 2007) is effective in treating ADHD or Tourette syndrome and comorbid sleep disorder. Caffeine restriction can be helpful. Low-dose valproic acid has been shown to be effective in a small case series of adults.

A study by Blumer et al found that zolpidem failed to improve insomnia in children and adolescents with ADHD. [21] The hypnotic efficacy of zolpidem was compared with that of placebo in children aged 6-17 years who experienced insomnia associated with ADHD. Patients were randomized to receive either zolpidem (0.25 mg/kg/day, not exceeding 10 mg/day total) or placebo. After 4 weeks of treatment, baseline-adjusted mean change in latency to persistent sleep did not differ significantly between the zolpidem and placebo groups.

In patients with circadian rhythm disorders, melatonin may be used. Melatonin acts directly on suprachiasmatic nuclei (the opposite of the effect of light on phase shifts). Phase delay requires morning dosing of melatonin; advanced sleep phase syndrome requires evening dosing (0.5 to 5 mg about 5 to 5.5 hours before bedtime). [20]  Ramelteon, a melatonin receptor agonist, is a US Food and Drug Administration (FDA)–approved medication for the treatment of insomnia in adults. A new medication, tasimelteon, has been approved by the FDA for the treatment of non–24-hour disorder in totally blind adults. Tasimelteon is also a melatonin receptor agonist.

Other common pharmacologic interventions include central alpha-2 agonists and antihistamines, even though little data support their use. In one recent survey, one third of pediatricians reported using clonidine for sleep onset, nighttime awakening, early morning awakening problems, and parasomnias. Central alpha-2 agonists may decrease nightmares associated with trauma. [22] Antihistamines were the most commonly used medication for treating sleep disorders. [23] In a larger study, physicians also commonly prescribed benzodiazepines 15% and antidepressants (trazodone) 6%. [24]

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