Snooze strategies for the young and restless

CaseJL, a 14-year-old female, presents to the pharmacy inquiring about the highest dose of melatonin she can safely use to treat insomnia. For the past two months, she has been having difficulty falling asleep as well as staying asleep, frequently waking up in the middle of the night and struggling to return to sleep. Her mother recommended melatonin, which JL has been taking nightly for the last six weeks. She started at a dose of 1 mg but has gradually increased up to 6 mg in the last two weeks. JL recently started high school and has been drinking four to five cups of coffee daily due to increased workload. She does not have a consistent bedtime or waking time and has noticed fatigue and difficulty concentrating in class due to lack of sleep. JL does not take any other medications, has no known allergies, and wants to know how to best resolve her sleep problems.BackgroundQuality sleep is vital for healthy development, both physically and mentally. Sleep deprivation and disorders are widespread among children and adolescents.Insomnia can be defined as difficulty falling asleep, staying asleep or early morning awakening with inability to return to sleep, with symptoms causing significant distress or impairment of function. Symptoms must occur at least three nights/week and can be acute ( 3 months).1,2 Insomnia may present with comorbid sleep disorders, psychiatric conditions or as an independent disorder.1-3 As such, it is vital to get a detailed patient history to screen for comorbid sleep disorders (Table 1) and risk factors such as medications or medical/psychiatric conditions (Figure 1), which may warrant referral for further investigation.Treatment approach for children and adolescents Nonpharmacologic treatmentNonpharmacologic approaches are first-line for insomnia, especially in those under six years of age.1-3 Cognitive behavioural therapy for insomnia (CBT-I) is a multimodal approach supported by robust evidence, including components such as stimulus control and sleep hygiene (see Table 2).1-4 Behavioural modifications may generate long-lasting benefits, whereas sleep improvements linked to medications tend to diminish once the medication is discontinued. A behavioural technique that may be used as an additional approach for infants or younger children is the Ferber method; it employs graded extinction, gradually reducing parental attention to a crying infant.2Pharmacologic interventions should be considered only if CBT-I proves ineffective or is not accessible. Referral to an appropriate care provider for further evaluation and/or management should be considered if nonpharmacologic measures have been adequately tried and if optimal doses of nonprescription or natural health products are ineffective after three nights or required for > 7 consecutive days.1Pharmacologic treatmentThe use of pharmacologic treatments for pediatric insomnia is limited by the scarcity of high-quality evidence and potential risk of side effects.Nonprescription drugsDiphenhydramine is a first-generation antihistamine with significant sedative effects. It may be used short-term for insomnia associated with histamine-mediated sleep disturbances, such as those related to allergies or atopic dermatitis.2 Efficacy in children for insomnia is variable, with some benefit in children two to 12 years of age in reducing sleep latency, increasing sleep duration and reducing the number of nighttime awakenings.7 However, antihistamines should be recommended with caution for insomnia as they may cause cognitive impairment, increased risk of falls, tolerance, dependence, withdrawal and rebound effects.1,2,7Natural health productsMelatonin is an exogenous synthetic hormone produced by the pineal gland in the brain. It is commonly referred to as the “sleep hormone” because of its crucial role in regulating our sleep-wake cycle. As the evening approaches, melatonin levels naturally rise, promoting the initiation of sleep. Conversely, during the daytime, melatonin levels decrease, aiding in our ability to stay alert and awake.For those dealing with specific sleep-related challenges, melatonin has become a widely used solution to restore the sleep-wake cycle. It can be used for insomnia at doses of 0.3–5 mg in children and adolescents, with doses up to 10 mg studied in children with autism.3,7 It provides some benefit in children with delayed sleep-onset insomnia, with much of the data being derived from children with autism or attention-deficit hyperactivity disorder.2-4,8 A systematic review demonstrated significant improvements in sleep latency and duration.4 Side effects include fatigue, dizziness, headache and hyperactivity.3,9,10There is little evidence for melatonin use long-term for treatment of insomnia (> 4 weeks), and some conflicting evidence regarding potential suppression of the hypothalamic-gonadal axis, which may affect pubertal development and lower nocturnal melatonin levels.3,9-11 Concern has also been raised based on the 530% increase in the number of calls related to pediatric melatonin ingestions to US Poison Control Centers from 2012 to 2021.12 While melatonin supplementation is generally considered safe across a range of doses, experts wonder whether its use may be masking underlying issues.12,13 In addition, as melatonin is classified as a Natural Health Product in Canada, it is not as strictly regulated, thereby lending itself to potential quality assurance issues.14,15 For example, an analysis of 30 melatonin products in 2017 in Ontario found that 71% varied by greater than 10% of their labelled potency.14Overall, melatonin may be a safe adjunct to nonpharmacologic therapy in pediatric insomnia, particularly for children with sleep-onset insomnia or delayed sleep phase syndrome and learning difficulties, autism or attention-deficit hyperactivity disorder, but use should be limited to one week.1 Melatonin should not be used as chronic monotherapy as it may overshadow the use of more effective behavioural treatments and the need for further assessments.L-tryptophan is available without a prescription at low doses (< 220 mg).2 There is limited evidence for its use, but it may be beneficial at higher doses for primary parasomnias in children; as such, referral to a primary care provider is required.1,16Valerian should be avoided due to lack of evidence, variation in preparations, and risk of hepatotoxicity.1Prescription pharmacologic treatmentsSedatives and hypnotics such as “z-drugs” (e.g., zopiclone, zolpidem) should be avoided in this population due to limited demonstrated efficacy and risk of side effects, including impaired memory and cognition, as well as risk of abuse.1,2Case analysis and recommendationJL has tried melatonin at an optimized dose for more than seven days with limited benefit. As such, it is inappropriate to recommend higher doses for treatment of insomnia, and JL should be advised to discontinue melatonin. As poor sleep hygiene habits (e.g., inconsistent sleep schedules, caffeine intake before bedtime) are likely contributing to JL’s insomnia, you should highlight and encourage the importance of CBT-I, focusing on strategies such as reducing caffeine intake and avoiding coffee at least four hours prior to bedtime. Counsel JL on sleep hygiene practices and encourage maintaining a sleep diary in order to target specific behaviours/patterns contributing to insomnia. Also discuss stimulus control therapy, including avoiding daytime naps and light-emitting devices when trying to sleep.1You make a plan to follow up with the patient in seven days to monitor improvement in sleep and daytime functioning. Referral is not immediately required for JL as she does not present with atypical sleep behaviours (Table 1), drug-induced causes of insomnia, or unmanaged concurrent medical/psychiatric conditions that may warrant investigation (Table 2). Advise the patient to follow up with their primary care provider if insomnia persists despite seven days of nonpharmacologic strategies in order to investigate underlying causes of insomnia.Dr. Nardine Nakhla is a practising community pharmacist and a faculty member at the University of Waterloo School of Pharmacy. The author thanks Sumani Vij, PharmD, for co-authorship of this article.References:Kim DD, Procyshyn RM, Barr AM. Insomnia. In: Compendium of Therapeutics Choices. Canadian Pharmacists Association. Updated October 14, 2022. (accessed January 15, 2024).Khullar A. Insomnia. In: Compendium of Therapeutic Choices. Canadian Pharmacists Association. Updated February 22, 2022. https://cps.pharmacists.ca/search (accessed September 7, 2023).Esposito S, Laino D, D’Alonzo R, et al. Pediatric sleep disturbances and treatment with melatonin. J Transl Med 2019;17(1):77. Published March 12, 2019. doi:10.1186/s12967-019-1835-1.McDonagh MS, Holmes R, Hsu F. Pharmacologic treatments for sleep disorders in children: a systematic review. J Child Neurol 2019;34(5):237-47. doi:10.1177/0883073818821030.Ontario College of Pharmacists. Minor ailments. Updated 2023. (accessed September 7, 2023).Pharmacy Association of Nova Scotia. Assessing and prescribing for minor ailments. Updated 2023. https://pans.ns.ca/public/pharmacy-services/assessing-prescribing-minor-ailments (accessed September 7, 2023).Owens, JA. Pharmacotherapy for insomnia in children and adolescents: a rational approach. In: Chervin RD, Eichler AF, ed. UpToDate; June 2022. (accessed September 7, 2023).Bruni O, Alonso-Alconada D, Besag F, et al. Current role of melatonin in pediatric neurology: clinical recommendations. Eur J Paediatr Neurol 2015;19(2):122-33. doi:10.1016/j.ejpn.2014.12.007.Health Canada. Melatonin and neurologic adverse reactions in children and adolescents. Health Product InfoWatch. Updated March 2016. (accessed September 7, 2023).Malow BA, Findling RL, Schroder CM, et al. Sleep, growth, and puberty after 2 years of prolonged-release melatonin in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 2021;60(2):252-261.e3. doi:10.1016/j.jaac.2019.12.007.Van Geijlswijk IM, Mol RH, Egberts TC, et al. Evaluation of sleep, puberty and mental health in children with long-term melatonin treatment for chronic idiopathic childhood sleep onset insomnia. Psychopharmacology (Berl) 2011;216(1):111-20. doi:10.1007/s00213-011-2202-y.Cohen PA, Avula B, Wang YH, et al. Quantity of melatonin and CBD in melatonin gummies sold in the US. JAMA 2023;329(16):1401-2. doi: 10.1001/jama.2023.2296.Taggart K. With melatonin supplement use on the rise, experts ask if it should be prescription-only. Canadian Healthcare Network, May 5 2022. (accessed September 7, 2023).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):275-81.Government of Canada. 2015 Reporting on compliance monitoring: testing of natural health products for vulnerable populations. Government of Canada. Updated August 2021. (accessed January 15, 2024).Van Zyl LT, Chung SA, Shahid A, et al. L-tryptophan as treatment for pediatric non-rapid eye movement parasomnia. J Child Adolesc Psychopharmacol 2018;28(6):395-401. doi:10.1089/cap.2017.0164.Lucien JN, Ortega MT, Shaw ND. Sleep and puberty. Curr Opin Endocr Metab Res 2021;17:1-7. doi: 10.1016/j.coemr.2020.09.009.Lexi-Comp Inc. Diphenhydramine (systemic). In: Lexi-Drugs. Updated September 9, 2023. (accessed September 9, 2023).

Snooze strategies for the young and restless

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