Medication Summary
The goals of pharmacotherapy are to improve sleep maintenance and treat nocturnal enuresis. Many of the medications described below are used 'off-label' and are not approved by the US Food and Drug Administration (FDA) for adolescents and children.
Vasopressin-Related
Class Summary
Desmopressin is a synthetic antidiuretic hormone with actions mimicking vasopressin. It is used for treating enuresis.
Desmopressin (DDAVP)
Desmopressin is used to treat primary nocturnal enuresis in children older than 6 years. It increases the cellular permeability of the collecting ducts, resulting in reabsorption of water by the kidneys.
Antidepressants, TCAs
Class Summary
Tricyclic antidepressants are used for treating narcolepsy and enuresis. Scant data exist to support their use in childhood narcolepsy. Sudden death has been reported in 8 children, possibly related to use of imipramine and desipramine; findings have been inconclusive about the causes of these deaths. No FDA indication exists for use of these agents in children with narcolepsy and enuresis.
Imipramine (Tofranil, Tofranil PM)
Imipramine inhibits the reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at the presynaptic neuron. It may be useful for treating pediatric attention deficit hyperactivity disorder (ADHD), as well as enuresis and, possibly, pediatric-onset narcolepsy.
Melatonin Receptor Agonists
Class Summary
In patients with circadian rhythm disorders, melatonin agonists may be used. Melatonin acts directly on suprachiasmatic nuclei. Use of OTC melatonin in children is recommended to be brief and not to exceed 10 mg per day. [26]
Melatonin
Melatonin is used to treat circadian rhythm disturbances in blind patients without light perception. Use in children is recommended to be brief and not to exceed 10 mg per day. The dose of melatonin will vary depending on the formulation. Over-the-counter forms of melatonin vary in quality and reliability.
Ramelteon (Rozerem)
Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and to be involved in maintaining circadian rhythm and normal sleep-wake cycles. Ramelteon is indicated for insomnia in adults characterized by difficulty with sleep onset.
Nonbenzodiazepine Hypnotics
Class Summary
Studies of the use of sedative-hypnotics to treat sleep disorders are limited to adults, and no FDA indications are approved for children younger than 18 years.
Eszopiclone (Lunesta)
Eszopiclone is a nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown but is believed to involve interaction with gamma-aminobutyric acid (GABA) receptors at binding domains close to, or allosterically coupled to, benzodiazepine receptors.
Eszopiclone is indicated for treatment of insomnia in adults by decreasing sleep latency and improving sleep maintenance. It has a short half-life (6 hours). Higher doses (ie, 2 mg for elderly and 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses (ie, 1 mg for elderly and 2 mg for nonelderly adults) are suitable for treating difficulty in falling asleep.
Anticonvulsants
Class Summary
Valproic acid was efficacious in small case series for adults with RLS and PLMS.
Valproic acid (Depakene, Depakote, Stavzor)
It is likely that all forms of valproic acid have similar efficacy. The following preparations can be used: 250-mg tablet, 125-mg sprinkle capsule, or 250 mg/5 mL liquid (US preparations).
Dopamine Agonists
Class Summary
Preliminary efficacious results for treatment using these agents have been noted in youths with restless legs syndrome (RLS) and periodic limb movement during sleep (PLMS). Findings are based on nonrandomized non–placebo-controlled study.
Pergolide was withdrawn from the US market on March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. Do not abruptly stop pergolide. Health care professionals should assess patients’ need for dopamine agonist therapy and consider alternative treatment. If continued treatment with a dopamine agonist is needed, another such agent should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.
Pergolide (Permax)
Withdrawn from US market. Pergolide is not FDA-approved for RLS or PLMS. It is a potent and long-acting dopamine agonist that reduces tonic stimulation of dopaminergic D2 receptors located on intrastriatal cholinergic neurons.
central alpha-2 agonist
Central alpha-2 agonist
clonidine
Antihypertensive used for many decades to treat insomnia in children. Now it is currently approved in extended release form for the treatment of Attention Deficit Hyperactivity Disorder. The benefit of sedation wears off in several weeks but may have continued benefit for reducing nightmares associated with trauma (insert new reference Belkin MR, Schwartz TL. Drugs in Context 2015; 4: 212286. DOI: 10.7573/dic.212286 1 of 5 ISSN: 1740-4398). Main side effects are sedation and dizziness. Duration of effect is usually 2 to 4 hours so may result in nighttime awakening unless extended release is prescribed
