Medications for pediatric insomnia: What clinicians need to know

Chronic insomnia refers to difficulty in initiating or maintaining sleep despite adequate opportunity for sleep and is associated with some form of daytime impairment.¹ In children, it may also refer to resistance to going to bed on an appropriate schedule or difficulty sleeping without the presence or intervention of a parent or caregiver. Symptoms occur at least 3 times per week for at least 3 months.

Insomnia is a common presenting sleep complaint. Difficulties with initiating and/or maintaining sleep have a prevalence of about 20% to 25% in children and 25% to 35% in adolescents.^2,3 The prevalence of insomnia is even higher in those with chronic medical conditions, as well as psychiatric and neurodevelopmental disorders, with a prevalence of greater than 80%.⁴ These sleep difficulties lead to nighttime sleep that is less than what is recommended for age (Table⁴).

Insufficient nighttime sleep in children and adolescents has been shown to have deleterious effects. Physical, neurocognitive, and behavioral consequences have been associated with poor sleep.⁵ Obesity has been shown to correlate with short sleep duration. Lack of sleep affects a child’s neurocognitive functioning, including attention, memory, and academic performance. Children with inadequate sleep are at greater risk for internalizing and externalizing behaviors, as well as symptoms of attention deficit and hyperactivity. It is thus imperative that insomnia be identified and managed appropriately.

Approach to a child with insomnia

The approach to a child with insomnia begins with a thorough sleep history evaluation. It is essential to evaluate for and manage other conditions, including behavioral, medical, psychiatric, and environmental issues that may be contributing to the sleep difficulties. Sleep hygiene should be optimized (Figure 1).

Sleep hygiene measures and behavioral modifications are considered first-line treatment for insomnia, particularly for typically developing children.⁶ Behavioral treatments for insomnia in young children have been shown to lead to significant improvements in sleep onset latency and in the frequency and duration of night awakenings.³ There are several components to behavioral therapy, and a combination of these is often used (Figure 2).³

If improving sleep hygiene and behavioral therapy, as well as managing conditions or external factors that may be contributing to sleep difficulties, do not lead to significant improvement in sleep, pharmacological therapy may be considered. Medications are not generally considered as first-line treatment for insomnia and are rarely appropriate for a typically developing child. Pharmacological therapy should always be supplemented by appropriate sleep hygiene and behavioral measures. Currently, there are no FDA-approved medications for pediatric insomnia in the United States, but both over-the-counter and prescription medications have been used off-label for pediatric insomnia. When considering medications for insomnia, treatment goals should be realistic and established, and the shortest possible treatment duration should be aimed for. This article will review the more common over-the-counter and off-label prescription medications used for pediatric insomnia.

Over-the-counter medications

Melatonin

Melatonin is one of the most frequently prescribed drugs in children and adolescents with sleep problems.⁷ It is a neurohormone that is primarily synthesized in the pineal gland. Its synthesis and secretion are inhibited by light and regulated by the circadian clock located in the suprachiasmatic nucleus.^8,9 It has a soporific effect, leading to a decrease in sleep onset latency of about 18 minutes and an increase in total sleep time of about 30 minutes (based on sleep diaries) in otherwise healthy children and adolescents with chronic insomnia.¹⁰ Short-term use of melatonin may be considered in this group if nonpharmacological interventions have not been successful and daytime impairment is present. Its use should be under the supervision of a medical provider. Melatonin is started with the lowest possible dose (0.5 mg) and titrated as indicated on a weekly basis. It is given 30 to 60 minutes before the desired bedtime. Recommended dosage range for melatonin in typically developing children is as follows: up to 1 mg in toddlers (2 to 3 years of age); up to 2 mg in preschoolers (4 to 5 years of age); up to 3 mg in school-age children (6 to 10 years of age); and up to 5 mg in older school-age children and adolescents.⁶ Melatonin is usually not recommended in children younger than 2 years of age, as there are no studies assessing its efficacy and safety in this age group, and most sleep disorders in this age group are behavioral in nature.⁶ Melatonin should be used in the shortest duration possible, and regular clinical reevaluation should be done to assess efficacy, adverse effects, and ongoing need.

In children with neurodevelopmental disorders, including autism, melatonin combined with behavioral sleep interventions is an effective treatment for insomnia.^11,12 Individuals with autism have been shown to have decreased nocturnal melatonin secretion.⁹ In one assessment, sleep onset latency decreased by 28 to 45 minutes, and total sleep time increased by 22.4 to 57 minutes.¹¹ Melatonin dosing in children with neurodevelopmental disabilities varies slightly from dosing in otherwise normal or typically developing children. Initial dosages usually range from 1 to 3 mg (up to 5 mg in adolescents), with the adjustments being made in 1- to 2-week intervals up to a maximum dose of 10 mg.⁷ It is also given 30 to 60 minutes before the desired bedtime. Children with neurodevelopmental disorders typically need longer-term use of melatonin.

Melatonin is available as oral liquid, soft chew gummies, tablets, capsules, tea, lozenges, and oral spray.¹³ The tablets and capsules come in immediate-release and extended-release formulations. The immediate-release formulations help with sleep-onset insomnia but have minimal effect on sleep-maintenance insomnia. The extended-release formulations may help with night awakenings, increasing total sleep time.⁹ However, there are limited studies on extended-release formulations, and there is currently insufficient evidence to determine their efficacy over immediate-release melatonin in children.¹¹  In the United States, the melatonin receptor agonist ramelteon is FDA approved for the treatment of insomnia in adults, while tasimelteon is approved for the treatment of non–24-hour sleep-wake disorder in adults and sleep-wake disorder in Smith-Magenis syndrome.⁹

Melatonin is generally well tolerated and not associated with serious adverse events. Adverse effects with short-term use include fatigue, somnolence, vomiting, cough, mood swings, increased excitability, headaches, and rash.¹¹ However, the impacts from long-term use, including effects on pubertal development, remain uncertain.

Melatonin is considered a dietary supplement and is not regulated by the FDA. Significant variations in reported melatonin content have been reported, with 71% of 31 analyzed melatonin supplements not meeting their label claim within a 10% margin.¹⁴ Melatonin content was shown to range from –83% to +478% of the labeled content. Additionally, serotonin, a controlled substance, was found in about 26% of the supplements tested. It is thus recommended that supplements verified by the United States Pharmacopeia be used.

Diphenhydramine

First-generation antihistamines, such as diphenhydramine, can cause sedation and have thus been used off-label to manage insomnia. Diphenhydramine is widely used for pediatric insomnia despite limited evidence for its efficacy, with only 1 study looking at its effectiveness in children aged 2 to 12 years with sleep disorders.¹⁵ This study showed that diphenhydramine at a dose of 1 mg/kg was significantly better than placebo in reducing sleep onset latency and number of awakenings but had only a marginal effect on total sleep duration. However, a randomized controlled trial of diphenhydramine in infants aged 6 to 15 months showed no improvement in night awakenings on diphenhydramine.¹⁶ This trial was stopped early due to the demonstrated lack of effectiveness of diphenhydramine.

Diphenhydramine is generally well tolerated in children and is widely available. It has a rapid onset of action and has minimal effects on sleep architecture.^7,17 However, it can cause adverse effects, including anticholinergic symptoms (urinary retention, dry mouth, dry eyes, constipation, arrhythmias, confusion), next-day sedation, and cognitive and psychomotor impairment.^18,19 It can also cause paradoxical excitation and confusion in children. Tolerance to its sedative effects tends to develop rapidly, necessitating increases in dosing, which may lead to an increase in adverse effects.¹⁸

Diphenhydramine is available as liquid, tablet, capsule, and injectable formulations. It is often a component of over-the-counter flu medications. Recommended dosing for pediatric insomnia is up to 0.5 mg/kg/day (up to a maximum of 25 mg).¹⁹ Given its unfavorable adverse effect profile and the tendency to develop tolerance to its sedative effects, diphenhydramine is best suited only for short-term or occasional use, particularly for children with comorbid atopic disease that may benefit from an antihistamine.

Off-label prescription medications

As many as 20% of children and 37% of older youth without comorbid psychiatric diagnoses are given prescription medication within a week of being diagnosed with insomnia.²⁰ The most common medications prescribed in children are α₂-adrenergic agonists, hydroxyzine, and trazodone. In older youth without psychiatric comorbidity, trazodone is the most common prescription medication given for insomnia.²⁰

α₂-adrenergic agonists

Clonidine is an α₂-adrenergic agonist that is approved by the FDA for hypertension and attention-deficit/hyperactivity disorder (ADHD).^17,21 It is often prescribed in children with ADHD to reduce hyperactivity, impulsiveness, and inattention. Given its sedative effect, it is also prescribed off-label for pediatric insomnia, but there is limited evidence for this indication.²² Prior studies showing improvement in sleep were limited to retrospective chart reviews and case series, usually in children with neurodevelopmental disorders. There are no well-controlled trials of clonidine for pediatric insomnia.

Off-label dosing of clonidine for pediatric insomnia is 0.05 to 0.2 mg at bedtime.²¹ It is rapidly absorbed, with an onset of action within 1 hour and peak effect in 2 to 4 hours.¹⁷ It is available as an oral suspension and tablets, and as a transdermal patch for ADHD. Adverse effects include hypotension, bradycardia, dizziness, dry mouth, and irritability. Clonidine has a narrow therapeutic index. Rebound hypertension may occur with sudden discontinuation.

Clonidine may be considered for children with ADHD and other neurodevelopmental disorders if sleep hygiene, behavioral therapy, and melatonin have not led to significant improvements in sleep. There is not enough evidence to recommend its use in otherwise healthy, typically developing children.

Guanfacine is another α₂-adrenergic agonist that is used in children with ADHD. It is associated with less sedation, and studies on the use of long-acting guanfacine for insomnia in children with ADHD or autism have not shown significant benefit.¹⁹

Hydroxyzine

Like diphenhydramine, hydroxyzine is a first-generation antihistamine, but it is available only by prescription. It is used in the management of pruritus due to allergic conditions, for symptomatic relief of anxiety, and as a sedative prior to surgery. Given its sedative effect, it is used off-label for the management of insomnia, though there are no controlled studies supporting its use for insomnia in children. In adults, a systematic review demonstrated mixed efficacy for insomnia^.23

Hydroxyzine is given at a dose of 0.5 to 1 mg/kg. It is available as syrup, tablets, capsules, and intramuscular injection. Adverse effects include urinary retention, dry mouth, constipation, tachycardia, next-day drowsiness, and confusion. Tolerance to its sedative effects can develop. As with diphenhydramine, hydroxyzine is poorly suited for long-term use and is more appropriate for short-term or occasional use.

Antidepressants

Trazodone

Trazodone is an antidepressant in the serotonin antagonist and reuptake inhibitor class. It also blocks histamine receptors and may increase the secretion of melatonin from the pineal gland.²¹ It is approved for use in major depression in adults but has no FDA-approved use in pediatrics. Trazodone is one of the most sedating antidepressants available and is thus used off-label for insomnia.

There are no well-controlled studies on the efficacy of trazodone for pediatric insomnia. Evidence is limited to case reports, though trazodone is often prescribed for pediatric insomnia in the setting of mood or anxiety disorders.^19,22 It is given at an initial dose of 25 to 50 mg at bedtime (or 0.75-1 mg/kg/day), which is lower than the recommended dose for depression, and may be titrated up to 100 to 150 mg. It reaches peak levels in 0.5 to 1.5 hours. Trazodone is available as tablets, liquid formulations, and capsules. Adverse effects include morning drowsiness, dry mouth, headache/dizziness, hypotension, arrhythmias, and priapism.

Doxepin

Doxepin is a tricyclic antidepressant, but at low doses (< 10 mg/day, which is much less than dosing for depression) it has significant histamine receptor antagonist activity, with 800 times the potency of diphenhydramine at the H1 receptor.²¹ It improves sleep maintenance and early morning awakenings in adults and is FDA approved for adult sleep-maintenance insomnia. There are no controlled studies in children looking at the safety and efficacy of doxepin for insomnia, but a small retrospective study of children 2 to 17 years of age with insomnia showed improvement in both sleep initiation and maintenance.²⁴

Doxepin is given at a dose of 3 to 6 mg within 30 minutes of bedtime. It is available in 3-mg and 6-mg tablets for adult insomnia. It is also available as an oral concentrate and as capsules. Adverse effects include anticholinergic effects and paradoxical agitation.

Mirtazapine

Mirtazapine is an α₂-adrenergic 5-HT2 antagonist.²¹ It also blocks histamine H1 receptors. It is FDA approved for depression in adults and has been used off-label for insomnia, as it produces a high degree of sedation at low doses. A small open-label study of mirtazapine, which included children with autism spectrum disorder and other forms of pervasive developmental disorders, showed improvement in sleep quality in about one-third of the subjects.²⁵

Mirtazapine is available as tablets and orally disintegrating tablets. It is started at a dose of 7.5 mg.²⁵ Adverse effects include weight gain, irritability, and daytime sleepiness.

Conclusion

In summary, nonpharmacological interventions, including sleep hygiene, behavioral therapy, and management of conditions or external factors that affect sleep, remain the first line of treatment for pediatric insomnia. Medications may be considered only if there is no significant improvement with these nonpharmacological interventions.

Pharmacological interventions should always be integrated with sleep hygiene as well as behavioral and environmental modifications. Melatonin has the most evidence supporting its use, both for typically developing children and for children with neurodevelopmental disorders, and is generally well tolerated. The rest of the medications do not have robust data supporting their efficacy and safety for pediatric insomnia, and caution should be exercised when prescribing them. Antihistamines may be beneficial for short-term or occasional use only, as they have an unfavorable adverse effect profile. Clonidine may be considered in children with ADHD. There is limited evidence supporting the off-label use of trazodone, doxepin, and mirtazapine in pediatric insomnia, and their use is best limited to those with comorbid mood disorders.

References

1. Sateia MJ. International classification of sleep disorders-third edition: highlights and modifications. Chest. 2014;146(5):1387-1394. doi:10.1378/chest.14-0970
2. Fernandez-Mendoza J, Lenker KP, Calhoun SL, et al. Trajectories of insomnia symptoms from childhood through young adulthood. Pediatrics. 2022;149(3):e2021053616. doi:10.1542/peds.2021-053616
3. Meltzer LJ, Wainer A, Engstrom E, Pepa L, Mindell JA. Seeing the whole elephant: a scoping review of behavioral treatments for pediatric insomnia. Sleep Med Rev. 2021;56:101410. doi:10.1016/j.smrv.2020.101410
4. Paruthi S, Brooks LJ, D’Ambrosio C, et al. Recommended amount of sleep for pediatric populations: a consensus statement of the American Academy of Sleep Medicine. J Clin Sleep Med. 2016;12(6):785-786. Published 2016 Jun 15. doi:10.5664/jcsm.5866
5. Liu J, Ji X, Pitt S, et al. Childhood sleep: physical, cognitive, and behavioral consequences and implications. World J Pediatr. 2024;20(2):122-132. doi:10.1007/s12519-022-00647-w
6. Melatonin Task Force; Owens J, Simakajornboon N, Kotagal S, Gringras P; International Pediatric Sleep Association (IPSA) Practice and Policy Committee and the IPSA Board of Directors. Melatonin use in typically developing (TD) children: International Pediatric Sleep Association (IPSA) expert consensus recommendations for healthcare providers. Sleep Med. 2025;128:127-129. doi:10.1016/j.sleep.2025.02.002
7. Esposito D, Belli A, Ferri R, Bruni O. Sleeping without prescription: management of sleep disorders in children with autism with non-pharmacological interventions and over-the-counter treatments. Brain Sci. 2020;10(7):441. doi:10.3390/brainsci10070441
8. Rolling J, Rabot J, Schroder CM. Melatonin treatment for pediatric patients with insomnia: is there a place for it? Nat Sci Sleep. 2022;14:1927-1944. doi:10.2147/NSS.S340944
9. Lalanne S, Fougerou-Leurent C, Anderson GM, et al. Melatonin: from pharmacokinetics to clinical use in autism spectrum disorder. Int J Mol Sci. 2021;22(3):1490. doi:10.3390/ijms22031490
10. Edemann-Callesen H, Andersen HK, Ussing A, et al. Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendation. EClinicalMedicine. 2023;61:102048. doi:10.1016/j.eclinm.2023.102048
11. Kotagal S, Malow B, Spruyt K, et al. Melatonin use in managing insomnia in children with autism and other neurogenetic disorders - an assessment by the International Pediatric Sleep Association (IPSA). Sleep Med. 2024;119:222-228. doi:10.1016/j.sleep.2024.04.008
12. Williams Buckley A, Hirtz D, Oskoui M, et al. Practice guideline: treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2020;94(9):392-404. doi:10.1212/WNL.0000000000009033
13. Shenoy P, Etcheverry A, Ia J, Witmans M, Tablizo MA. Melatonin use in pediatrics: a clinical review on indications, multisystem effects, and toxicity. Children (Basel). 2024;11(3):323. doi:10.3390/children11030323
14. Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275-281. doi:10.5664/jcsm.6462
15. Russo RM, Gururaj VJ, Allen JE. The effectiveness of diphenhydramine HCI in pediatric sleep disorders. J Clin Pharmacol. 1976;16(5-6):284-288. doi:10.1002/j.1552-4604.1976.tb02406.x
16. Merenstein D, Diener-West M, Halbower AC, Krist A, Rubin HR. The trial of infant response to diphenhydramine: the TIRED study—a randomized, controlled, patient-oriented trial. Arch Pediatr Adolesc Med. 2006;160(7):707-712. doi:10.1001/archpedi.160.7.707
17. Ekambaram V, Owens J. Medications used for pediatric insomnia. Psychiatr Clin North Am. 2024;47(1):87-101. doi:10.1016/j.psc.2023.06.006
18. Clark JH, Meltzer EO, Naclerio RM. Diphenhydramine: it is time to say a final goodbye. World Allergy Organ J. 2025;18(2):101027. doi:10.1016/j.waojou.2025.101027
19. Mammarella V, Randazzo L, Romano S, Breda M, Bruni O. Pharmacological management for insomnia in children and adolescents with autism and attention deficit and hyperactivity disorder. Expert Opin Pharmacother. 2025;26(9):1079-1098. doi:10.1080/14656566.2025.2508277
20. Bushnell G, Ivanenko A, Horton DB, et al. Psychiatric comorbidities and prescribing tendencies of sleep medications and related medications in young people with insomnia: a United States commercial claims-based analysis. Sleep. 2024;47(5):zsae057. doi:10.1093/sleep/zsae057
21. Bruni O, Angriman M, Melegari MG, Ferri R. Pharmacotherapeutic management of sleep disorders in children with neurodevelopmental disorders. Expert Opin Pharmacother. 2019;20(18):2257-2271. doi:10.1080/14656566.2019.1674283
22. Dhir S, Karim N, Berka H, Shatkin J. Pharmacological management of pediatric insomnia. Front Sleep. 2024;3:1389052. doi:10.3389/frsle.2024.1389052
23. Burgazli CR, Rana KB, Brown JN, Tillman F 3rd. Efficacy and safety of hydroxyzine for sleep in adults: systematic review. Hum Psychopharmacol. 2023;38(2):e2864. doi:10.1002/hup.2864
24. Shah YD, Stringel V, Pavkovic I, Kothare SV. Doxepin in children and adolescents with symptoms of insomnia: a single-center experience. J Clin Sleep Med. 2020;16(5):743-747. doi:10.5664/jcsm.8338
25. Posey DJ, Guenin KD, Kohn AE, Swiezy NB, McDougle CJ. A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2001;11(3):267-277. doi:10.1089/10445460152595586