TABLE E-1Common Medications for Pediatric Insomnia

TABLE e-1Common Medications for Pediatric Insomnia

Medication / Class - MOA / Dose (Range) / Effect, Onset &
Half-life (T½) / Common Side Effects / Relative Cost*
FDA status **
Non-prescription
Diphenhydramine / Anti-histamine
H1-receptor blocker / 0.5-1 mg/kg
(12.5-50 mg) / Reduce SOL.
Rapid onset (peak levels ~2 hr)
T½: 2-8 h / Daytime sleepiness; paradoxical excitation; anti-cholinergic side effects (nausea, urinary retention, dry mouth, constipation).
Watch for tolerance / $
A: Yes;12yr+
I: insomnia
Melatonin / Melatonin-receptor agonist. / For SOL:
1-3 mg
(1-10 mg);
For phase advance: 0.3-0.5 mg / Reduce SOL. Phase-advance.
Onset: 30-60 min
T½: 30-50 min / Bradycardia, hypotension, nausea, headache. / $
A: No
Prescription
Hydroxyzine / Anti-histamine
H1-receptor agonist / 0.6 mg/kg
(25-100 mg) / See Diphenhydramine
T½: 6-24 h / See Diphenhydramine / $
A: Yes; Pediatric
I: Sedation, Anxiety, other
Clonidine / Alpha-2 adrenergic agonist
Decrease NE release / 0.05-0.1 mg
(max 0.3-0.4 mg ÷ over 24h) / Reduce SOL, SWS and REM.
Onset ~ 1 h (peak 2-4 h)
T½: 6-24 h (8-12 h in children) / Hypotension, bradycardia, anti-cholinergic side effects, rebound hypertension with abrupt discontinuation.
Watch for tolerance / $$$
A: Yes; NotPediatric
I: ADHD, HTN
Guanfacine / Same as clonidine but more selective / 0.5-1 mg
(max 3-4 mg ÷ over 24h) / See Clonidine
T½: 17 h / See Clonidine / $-$$
A: Yes; 12 yr+
I: ADHD, HTN
Ramelteon / Melatonin receptor (MT1, MT2) agonist / 8 mg (adult) / Reduce SOL and increase TST.
Onset: ~45 min
T½: 1-2.6 h / CYP 1A2 metabolized
Avoid use with fluvoxamine (increases Ramelteon level) / $$$$$
A: Yes; NotPediatric
I: Insomnia
Clonazepam / GABAA receptor agonist / 0.25-0.5 mg
(0.5-2 mg adult) / Reduces SOL and night arousals; increase TST; also used for parasomnias.
Onset 20-60 min (peak 1-4 h)
T½: 30-40 h / Alters sleep structure (reduce SWS). Daytime sleepiness, rebound insomnia, impaired memory, dis-inhibition. Avoid if suspect untreated OSA due to muscle relaxation properties.
CYP 450 3A4 metabolized – caution with fluoxetine; increase CNS depression with alcohol or barbiturate. Watch for tolerance. / $-$$
A: Yes; Pediatric for seizure
I: Panic, Seizure
Zolpidem, / GABAA receptor agonist / 5-10 mg (tab)
1.75-3.5 mg (sublingual)
6.25-12.5 mg (extended release)
(adult doses)
0.25mg/kg (child) / Reduces SOL and night arousals; improves TST.
Onset: 30-60 min
T½: 2-3 h / Headache, amnesia, parasomnias, worsen OSA; less sedation than clonazepam. CYP 3A4 metabolized – caution with fluoxetine; increase CNS depression with alcohol, barbiturate.
Watch for tolerance. / $$
$$$$
A: Yes; Not Pediatric
I: Insomnia
Eszopiclone / Same as Zolpidem / 1-3 mg/dose
(adult doses) / Same as Zolpidem;
Onset: 30-60 min
T½: 5-7 h / Same as Zolpidem; Metallic taste. Longer T½ useful for sleep maintenance. / $$$$$
A: Yes; Not Pediatric
I: Insomnia
Zaleplon, / Same as Zolpidem / 5-10 mg/dose (adult doses) / Same as Zolpidem; not help TST.
Onset: 30-60 min
T½: 1-2 h / Same as Zolpidem but not CYP 3A4 metabolized. Shorter T½ useful for sleep onset, not sleep maintenance / $$$
A: Yes; Not Pediatric
I: Insomnia
Chloral hydrate / Unknown
CNS depressant / 25-50 mg/kg/dose
(max 1-2g) / Reduces SOL.
Onset: 30 min
T½: ~ 10 h (but 3-4 x longer for infants) / Daytime sleepiness, respiratory depression (avoid if suspect OSA), nausea, liver toxicity, CVS instability, caution with fluoxetine – prolonged sedation.
Watch for tolerance / $$
A: Yes; Pediatric
I: Insomnia, Sedation, other
Trazadone / Atypical antidepressant
Serotonin agonist / 20-50 mg / Reduces SOL, REM. Increases SWS.
Onset: 30-120 min
T½: biphasic; 3-6 h, 5-9 h / Dizziness, CVS – arrhythmia, hypotension, priapism, CNS overstimulation
CYP 450/2D6 – potentiates CNS depressants and other.
Watch for tolerance. / $-$$
A: Yes; Not Pediatric
I: Depression
Doxepin / Tricyclic with mixed effects:
H1, H2 histamine receptor blocker; NE reuptake inhibitor / 10-50 mg
(for initial insomnia) (3-6 mg for middle insomnia)
(max 300 mg/24 hr) / Reduce SOL; Improve sleep maintenance
Onset ~30 min
T max 3.5 hr
T½: 15.3 hr / Constipation, nausea, dizziness, urinary retention, hypotension, ventricular arrhythmia, nephrotoxicity, suicidal thoughts / $-$$
A: Yes; Not Pediatric
I: Insomnia

Abbreviations: B: Benzodiazepine; CNS: central nervous system; CVS: cardiovascular system; CYP: cytochrome; GABA: gamma-aminobutyric acid; GABAA: GABA-A receptor agonist; MOA: Mechanism of action; NE: norepinephrine; REM: rapid eye movement sleep; SOL: sleep onset latency; SWS: slow wave sleep; TST: total sleep time.

* Costs for one dose x 30-days: $: < $25; $$: $26-50; $$$: $51-100; $$$$: $101-200; $$$$$: $201+

** FDA status: A: approved Yes/No; “Pediatric”or age range; I: FDA-approved indication