Table 3.

Pharmacological agents in childhood insomnia

MEDICATION	DOSING	SAFETY CONCERNS	PEARLS
Alpha-agonists (clonidine, guanfacine)	Oral clonidine 0.05mg at bedtime (titrated by 0.05mg every 5 days) Oral guanfacine 0.5mg at bedtime (gradual titration by 0.5mg every 5 days)	Cardiovascular risk at higher doses and overdose	Guanfacine is less sedating and has less anticholinergic and cardiovascular side effects compared to clonidine. Guanfacine is helpful in comorbid seizure disorders due to anticonvulsant effects; newer longer-acting formulation can be useful in treatment of attention deficit hyperactivity disorder (ADHD) and help with sleep maintenance. Rapid eye movement (REM) suppression may occur, resulting in REM rebound upon discontinuation Often prescribed to target sleep onset delay in children with ADHD
Melatonin and its receptor agonists (e.g., Ramelteon)	Clear dosing guidelines for melatonin unavailable in children 0.5–3mg/day (administered 2–3 hours prior to sleep onset)	Possible suppression of the hypothalamic-gonadal axis (caution in children with delayed puberty)	Often prescribed to target sleep onset delay in children with ADHD and developmental disorders More useful for chronobiotic rather than hypnotic properties (thus, useful in circadian rhythm sleep disorders) Effective doses may be higher in children with developmental disorders (up to 10mg/day). Ramelteon (melatonin-receptor agonist) has limited data for use in children Newer agents (Agomelatine) can have potential uses in treating comorbid anxiety and insomnia (due to melatonin agonist and serotonin antagonist properties)
Antihistamines	Diphenhydramine (0.5mg/kg, with maximum dose of 25mg/day) Hydroxyzine (0.5mg/Lb)	Daytime drowsiness, dry mouth, urinary retention, paradoxical hyperactivity, cardiac toxicity in overdose	Sedative effects through H1 receptor blocking properties Development of tolerance requiring escalating doses Anxiolytic and anticholinergic properties of antihistamines can potentiate substance abuse in adolescents.
Benzodiazepines (e.g., clonazepam, lorazepam) and benzodiazepine-receptor agonists [BZRAs] (zaleplon, zolpidem, eszopiclone)	Ultra-short half-life (zaleplon, 1–2 hours), short half-life (zolpidem, 2–3 hours), intermediate to long half-life (eszopiclone, 6 hours)	Behavioral disinhibition and agitation with aggression and impulsivity, paradoxical hyperactivity	Clonazepam useful in treatment for periodic limb movement disorder and in treatment of arousal parasomnias Limited use in children due to potential for abuse; none are approved for use in children by FDA. BZRAs have been shown to induce complex sleep-related behaviors (e.g., sleep eating and sleep walking); longer-acting medications (e.g., eszopiclone) are used mostly in adults due to lack of development of tolerance.
Antidepressants	Trazodone at lower doses (12.5–50mg/day) Tricyclics (amitriptyline, nortriptyline)	Priapism with trazodone; treatment- emergent anxiety and agitation; exacerbation of symptoms of restless legs syndrome with tricyclics; significant cardiotoxicity in overdose	Most tricyclics are potent REM sleep suppressants and suppress slow wave sleep Should be used at the lowest possible doses to avoid cardiac side effects Sedating antidepressants (e.g., mirtazapine) have limited data in children; rapid eye movement suppression by mirtazapine appears to be minimal.
Herbal supplements	Chamomile, lavender, tryptophan, kava kava	necrotizing hepatitis (kava kava); eosinophilia myalgia syndrome (tryptophan)	Use of herbal supplements have limited-to-no evidence of efficacy.