Sleep onset difficulties

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NICE state that evidence for use of melatonin has shown a total increase in sleep time of only 20 minutes and reduction in time taken to fall asleep of approximately 20 minutes.  There are still ongoing concerns over the lack of long-term safety data in children, and there is uncertainty as to the effect on other circadian rhythms including endocrine or reproductive hormone secretion.

http://www.sleepscotland.org/

Indication for therapy

It is well known that improving sleep patterns leads to a general improvement in health, behaviour and wellbeing. Any child being considered for a trial of melatonin must have:

1. significant sleep onset difficulties.

 AND

2. at least one of the following:

  • ocular visual impairment
  • severe to profound learning disabilities
  • neurological disorder, eg cerebral palsy
  • neurodevelopmental disorder, eg attention deficit hyperactivity disorder (ADHD) and autism.

Sleep disorders in children with neurological and neurodevelopmental disorders are very common. Causes include:

  • delayed brain maturation
  • altered function of sensory organs, especially vision
  • abnormalities of the sleep centres.

The particular types of sleep difficulties seen include:

  • delayed sleep onset
  • frequent wakening
  • early morning wakening
  • day-night reversal patterns. 

 

  • Melatonin may be prescribed to assist development of improved sleep patterns and behaviours, when and only once, appropriate behavioural sleep interventions fail.
  • It may also be viewed as an alternative to sedatives and hypnotics, which have adverse side-effects.
Behavioural measures
  • Drug therapy must only be commenced after behavioural interventions and sleep hygiene measures have been carried out.
  • Behavioural modification and appropriate sleep hygiene measures may require a long period of adherence before benefit is seen and occasionally they are ineffective, just as medication can have unanticipated effects.
  • If melatonin is being considered, behavioural measures must be used first and maintained during the trial. The benefits of behaviour change continue longer over time than drugs.
  • Advice about sleep hygiene should be discussed with the family, backed up with written information (Appendix 3 and 4), and in consultation with the Health Visitor, School Nurse, Community Children’s Nurse or Community Nurse for Learning Disabilities, as appropriate.
Sleep diaries
  • Detailed sleep histories are key to the diagnosis of sleep disorders, which can be a major source of stress for the whole family and limited solutions are available.
  • Sleep diaries and parent information are vital.
  • Prior to a trial of melatonin, a baseline sleep diary should be completed to aid diagnosis of the type of sleep disorder (Appendix 1 and 2).
  • Further diaries are used to monitor effectiveness and influence decision making. Some children may have noticeable improvement in their sleep pattern after the first dose of melatonin. Others may not show improvement for several days or even weeks.
  • Assess and diagnose children with sleep onset difficulties and their suitability for treatment.
  • Ensure behavioural measures and sleep diaries have been followed and are ongoing.
NHS Highland recommends

Preferred option

Generic drug name

Melatonin

Formulation

3mg capsules

Status of medicine or treatment

Melatonin 3mg capsules are unlicensed in the UK and are included in Part 7U of the Scottish Drug Tariff.

Swallowing difficulties

The capsules can be opened and the contents given in a small drink or soft food. Can also be used this way to put through a gastrostomy.

Prescribing using VISION system

On the F3 drug navigator screen, there is a box called ‘Special’ this needs to be ticked (located top right-hand corner, next to the ‘Formulary’ box). Once this is activated, when you go into ‘search the drug dictionary’ to locate melatonin capsules 3mg, all the melatonin specials are listed and the 3mg capsules should be selected.

 Other melatonin products are not recommended other than in the circumstances detailed below.

Less preferred option

Generic drug name

Melatonin

Formulation

10mg capsules

 

In patients who have been prescribed 9mg and who have tolerated 9mg in capsules, it may be easier for the patient to prescribe one 10mg capsule rather than three 3mg capsules.

Status of medicine or treatment

Melatonin 10mg capsules are unlicensed in the UK.

Swallowing difficulties

The capsules can be opened and the contents given in a small drink or soft food. Capsules can also be opened and used in this way to put through a gastrostomy.

Specials

Prescribing and supply should be in accordance with the NHS Highland Guidance for prescribing and supply of specials and imported unlicensed medicines.

Dosing information

Route of administration

Oral

Recommended starting dose

Initially 3mg daily which can be increased to 6mg or 9mg if insufficient response after 1 to 2 weeks.

 

Give 30 minutes before bedtime, preferably on an empty stomach. Can take up to an hour to be effective.

Titration of dose

Increase to 6mg or 9mg depending on response after 1 to 2 weeks. If stable on a 9mg dose (3x3mg capsules) change to 1x10mg capsule.

Maximum dose

10mg daily. Extra benefits of doses above 10mg are uncertain.

Adjunctive treatment regimen

Behavioural measures and sleep diaries.

Conditions requiring dose adjustment

Non response (delayed time to sleep onset, disturbed sleep, early morning awakening).

Usual trial period

7 to 14 days.

Duration of treatment

Indefinite if significant sleep problem persists and patient continues to benefit.

Unlicensed Medicines and Off-Label Medicines
  • Unlicensed or off-label use of medicines becomes necessary if the clinical need cannot be met by licensed medicines; such use is supported by appropriate evidence and experience.
  • Prescribing medicines outside the terms of their Marketing Authorisation alters (and probably increases) the prescriber’s professional responsibility and potential liability.  
  • Unlicensed products may be classified as supplements, not pharmaceuticals, in their country of origin and may not be made under pharmaceutical Good Manufacturing Practices. The MHRA advises that they should therefore only be used as a last resort as variability in clinical effect of unlicensed formulations has been noted.
  • Highland Unlicensed and Off-label Medicines List.
Responsibilities of the prescriber
  • Ensure behavioural measures are ongoing.
  • Provide an understanding of potential side-effects and the requirement for monitoring to the patient and the patient’s parents. Obtain informed consent prior to therapy.
  • Monitor height, weight, growth and the onset of puberty/sexual development, particularly in children during long-term administration. Additionally, these should be monitored if melatonin is stopped.
  • Assess and monitor the patient’s response to treatment and check for possible complications. Assess - initially 3-monthly, then 6-monthly in the longer term.
  • Initiate and stabilise the patient on therapy and supply medicine for one further month after the dose has stabilised.
  • Stop melatonin for 1 week during a non-stressful period; repeat the sleep diary and review.
  • If therapy continues beyond children’s services, care should be transferred to young persons or adult services as appropriate.
Discontinuation
  • Discontinue if ineffective. Provide necessary supervision and support during drug discontinuation phase. Withdrawal of melatonin can be immediate. Monitor for recurrence of sleep disorders, depending on the frequency of use.
Responsibilities of patient/parent/carer
  • To attend hospital and GP clinic appointments.
  • Failure to attend appointments will result in medication being stopped.
  • To report adverse effects to their doctor.
Additional responsibilities
  • Any serious reaction should be reported to the Commission of Human Medicines (CHM) by whomever they are highlighted to.
  • Use the Yellow Card System to report adverse drug reactions. Yellow Cards and guidance on their use are available at the back of the BNF or online at www.mhra.gov.uk/yellowcard.
Transfer from Paediatric to Adult Care
  • As this group of patients move into adult care, consideration should be given to continuation of their therapy.
  • The principles in this policy apply equally to this group of patients as they become adults.
Cautions, contraindications and significant drug interactions
  • For cautions, contraindications and significant drug interactions see current relevant sections in the BNF for Children.
Supporting documentation – references
  • Banta S. Use of melatonin in children and adolescents: clinician’s and parent’s perspective. Child and Adolescent Mental Health, May 2008;13(2):82-84.
  • Bisht V., Beach S. Melatonin-Audit of prescribing practice for children in a rural population. Archives of Disease in Childhood. 2014;99:A64.
  • British Medical Association, Royal Pharmaceutical Society of Great Britain, Royal College of Paediatrics and Child Health, Neonatal and Paediatric Pharmacists Group. BNF for Children 2014-2015. London: BMJ Group; 2014. [on line] available from: http://www.medicinescomplete.com/mc/bnfc/current/ accessed 29/12/2014.
  • C Cummings; Canadian Paediatric Society Community Paediatrics Committee Melatonin for the management of sleep disorders in children and adolescents Paediatric Child Health 2012;17(6):331-3. Importing unlicensed medicines Important information relating to specific products Melatonin MHJRA: London [on line] available from: http://www.mhra.gov.uk/Howweregulate/Medicines/Importingandexportingmedicines/Importingunlicensedmedicines/ accessed 29/12/2014.
  • Cecil V et al. Melatonin for treatment of sleeping disorders in children with ADHD: a preliminary open label study. European Journal of Pediatrics, 2003;162:554-555.
  • Cochrane Library 2009 issue 3, Melatonin for the prevention and treatment of jetlag (review).
  • De Leersnyder H, Zisapel N, Laudon M. Prolonged-release melatonin for children with neurodevelopmental disorders. Pediatr Neurol [Internet]. 2011 [cited 2011 Jul];45(1):23-6. In: Ovid MEDLINE(R) [Internet]. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=medl&NEWS=N&AN=21723455.
  • ESUOM2: Sleep disorders in children and young people with attention deficit hyperactivity disorder: melatonin Published: 04 January 2013 NICE: London [online] available from: http://www.nice.org.uk/mpc/evidencesummariesunlicensedofflabelmedicines/ESUOM2.jsp accessed 19/9/2013.
  • Gringas P. When to use drugs to help sleep. Archives of Disease of Childhood, 2008;93:976-981.
  • Hoebert M et al. Long term follow up of melatonin treatment in children with ADHD and chronic sleep onset insomnia. Journal of Pineal Research, Aug 2009;47(1):1-7.
  • Jain S., Horn P., Simakajornboon N., Holland K., Glauser T.  Melatonin improves sleep in children with epilepsy: Results from a randomized, double-blind, placebo-controlled, cross-over study. Epilepsy Currents. 2014;14:442.
  • Jeraisy Majed DM Ba Armah A.L., Al Bekairy A., Mohiuddin B., Altwaijry W.  Effect of melatonin in neuro-developmentally disabled children with sleep disorders. Canadian Journal of Neurological Sciences. 2014;41:S21-S22.
  • London New Drugs Group Briefing – Melatonin in paediatric sleep disorders Sept 2008.
  • M Smits et al. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: A randomized placebo controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry, Nov 2003; 42(11):1286-1293.
  • Montgomery P et al. The relative efficacy of two brief treatments for sleep problems in young learning disabled children: a randomised controlled trial. Archives of Disease in Childhood, 2004; 89:125-130.
  • Owens J. Pharmacotherapy of paediatric insomnia. Journal of the American Academy of Child and Adolescent Psychiatry, Feb 2009;48(2):99-107.
  • QIS Evidence Note 14 – Melatonin to assist in the management of sleep disorders in children with neurodevelopmental disorders Dec 2006.
  • Ross C et al. Melatonin treatment for sleep disorders in children with neurodevelopmental disorders: an observational study. Developmental Medicine and Child Neurology’ 2002; 44:339-344.
  • Sweis D. The Uses of Melatonin. Archives of Disease in Childhood, 2005; 90:74-77.
  • Stores G. Medication for sleep-wake disorders. Archives of Disease in Childhood, 2003; 88:899-903.
  • T Shah et al. Administration of melatonin mixed with soft food and liquids for children with neurodevelopmental difficulties. Developmental Medicine and Child Neurology 2008, 50: 845-849.
  • Therapeutic Research Faculty. Melatonin. Natural Medicines Comprehensive Database, 2004.
  • van Geijlswijk IM, Mol RH, Egberts TC, Smits MG. Evaluation of sleep, puberty and mental health in children with long-term melatonin treatment for chronic idiopathic childhood sleep onset insomnia. Psychopharmacology (Berl) [Internet]. 2011 [cited 2011 Jul];216(1):111-20. In: Ovid MEDLINE(R) [Internet]. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=medl&NEWS=N&AN=21340475.

 

Appendix 1: Leaflet for parents - sleep diary

Appendix 2: Sleep diary

Appendix 3: Good advice on sleeping for primary age children

Appendix 4: Tips on helping secondary age children sleep

Appendix 5: Melatonin for sleep disorders in children and adolescents (information for patients and carers)

Editorial Information

Last reviewed: 31 March 2018

Next review: 31 March 2020

Author(s): Melatonin Working Group

Version: 5

Approved By: High-UHB.therapeuticportal@nhs.net

Reviewer Name(s): Sheila Watt