Melatonin in the treatment of sleep disorders in children and ...
GREATER MANCHESTER INTERFACE
On behalf of the
GREATER MANCHESTER MEDICINES MANAGEMENT
SHARED CARE GUIDELINE for melatonin in the treatment of Reference Number
sleep disorders in children and adolescents MELA09fnl
Pennine Care NHS Foundation Trust SHARED CARE GUIDELINE
Heywood, Middleton & Rochdale PCT
Tameside & Glossop PCT
Issue date 13 July 2009 Replaces on this website December 2007
document (written by Central Manchester and Manchester
Children’s University Hospitals NHS Trust)
Author(s)/Originator(s) Pennine Care NHS Foundation Trust
To be read in conjunction with the Melatonin patient information leaflet
following documents Melatonin information for medical practitioners
Review Date 3 July 2011
Approved by Interface Prescribing 12 October 2009
• Insomnia is a widespread problem in children with neurodevelopmental or
psychiatric disorders such as autistic spectrum disorder & attention deficit
hyperactivity disorder (ADHD).
• Although non-behavioural treatments, such as behavioural therapy can be
very effective in some forms of paediatric insomnia, children with
neuropsychiatric disorders tend to have a lower response rate to behavioural
• Currently there are no licensed treatments for sleep disorders in children in
• Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone produced by
the pineal gland during the dark hours of the day and night. It is used as a
treatment of sleep disorders in children.
• The use of melatonin is supported by NICE in their Clinical Guidelines on the
diagnosis and management of chronic fatigue syndrome/myalgic
encephalomyelitis (CFS/ME) in adults and children. The NICE guidelines
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states that melatonin may be considered for children and adolescents with
CFS/ME who have sleep difficulties, but only under specialist supervision.
• Pennine Care NHS Foundation Trust and associated PCTs. Acute Trust
3. Clinical condition being treated
• Insomnia is a common problem for children with sensory deficits and some
learning disabilities. It can be a symptom of childhood psychiatric disorders
such as depression and ADHD. Sleep disorders affect approximately 10%
of otherwise normal children and up to 80% of children with developmental
Indication for use:
1. Documented neurological or neuro-developmental disorder.
2. Documented severe, disrupted sleep disturbance.
3. Failure to respond to behavioural treatments.
The patient will usually have been asked to keep a 24 hour sleep
diary for a period of at least 7-10 days.
• Melatonin is a naturally occurring hormone produced by the pineal gland in a
circadian manner. The production of melatonin is suppressed by light and
serum melatonin levels are very low during most of the day. Melatonin is
involved in the induction of sleep and responds to darkness. The rise of
melatonin precedes the onset of sleep by about 90 minutes.
• Melatonin is thought to have its effect via GABA receptors.
• Since there is a link with circadian rhythms and it being a 'natural' product,
melatonin has been prescribed for the treatment of sleep disorders
underpinned by learning disability, autistic spectrum disorders and ADHD.
• Melatonin use should be monitored by specialist review every 6 months.
• The patient and carer should attend specialist review meetings and be given
information about sleep patterns, compliance, side effects, and response to
• Treatment decisions should be shared between patient, carer and the
4. Product information and treatment regimen to be used
NB Following the UK launch of Circadin (melatonin 2mg prolonged
release tablets), the Medicines and Healthcare products Regulatory
Agency (MHRA) has issued drug procurement advice stating that
unlicensed imports of melatonin will only be authorised in the case of a
special need. The licensed product should be used wherever possible,
including off-label use if deemed suitable by specialist.
(a) Circadin is the only UK licensed product which contains melatonin. It is a
2mg prolonged release tablet. It is licensed for the short-term treatment of
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primary insomnia characterised by poor quality sleep patterns who are aged
55 or over. The MHRA would prefer an ‘off-label’ licensed product be used if
it can meet the clinical need, than an unassessed, unlicensed product.
(b) If Circadin can not meet the clinical need, an imported product should be
used, which is licensed in the country of origin.
This would be Bio-Melatonin which is manufactured in Hungary by Pharma-
Nord and available as 3mg tablet (non-scored). It is manufactured in Good
Manufacturing Practice (GMP) inspected facilities in Denmark. In order for
the patient to receive supplies of this product the medical practitioner will
need to provide written conformation of special clinical need; this means the
medical practitioner must fill out a ‘Proforma letter of Special Clinical Need’.
This letter must be taken with the actual prescription to a Community or
Hospital Pharmacy for dispensing. The product will not be available straight
away as the Pharmacist will need to fax the letter to Pharma Nord for a
supply to be made to them and subsequently to the patient.
(c) If a different strength of immediate release melatonin product is required
then a product such as those manufactured by Penn Pharmaceutical
Services may be used. These are unlicensed products, although Penn
Pharmaceutical Services have a UK ‘specials’ license and their products are
manufactured in GMP inspected facilities. A ‘Proforma letter of Special
Clinical Need’ is not required to obtain a supply of this product.
For prolonged release melatonin (Circadin)
• Initially 2mg once at night and increased if necessary
• The dose should be taken 1-2 hours before bedtime and after food
• The tablets should be swallowed whole. They should NOT be crushed or
cut in half
For immediate release melatonin
• Initially 1-3mg at night, increasing after 1-2 weeks to 4-6mg (if response
or partial response).
• Maximum of 10mg/day (although 12mg has been used)
• The dose should be taken about an hour before bedtime.
• If the child wakes during the night, the same dose can be repeated
during the night
• Melatonin is available as a tablet, capsule, soluble tablet or liquid,
depending where the medication is obtained from
Special clinical need would be the overall reason for not using a licensed
product ‘off-label’. Effectiveness and side effect profile is similar, between
immediate-release and modified-release formulations of Melatonin. Factors
favouring use of single dose modified-release preparations would be
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licensing, issues around fluctuating control or compliance, individual
tolerance, and patient/ carer preference.
5. Regimen Management
a) Aspects of care for which the Specialist is responsible. The term Specialist
includes Child and Adolescent Psychiatrist, Paediatrician, or nominated
Advanced Practitioner/ Non Medical Prescriber (in agreement with their
• Direct assessment or supervision of specialist team assessment,
evaluation of prior treatment, and rationalisation of treatment with
• Informing patient/ carer of diagnosis, care plan, treatment including
side effects and ‘off-label’ use of melatonin, or use or unlicensed
product. Use of Patient Information Leaflets (PILs), user-friendly
information leaflets for children/ adolescents.
• Ascertaining patient/ family’s commitment to safe storage and handling
• Initiation and titration of melatonin to a suitable dose.
• Promoting access to any appropriate supporting therapies, carer
education, and appropriate school liaison.
• Minimum 6 monthly Specialist review appointments.
• Asking General Practitioners (GP) if they are willing to participate in
• Written correspondence to GP from Specialist Team, summarising
progress and recommendations for continued treatment.
• Ensure clear arrangements for GP back up, advice and support.
• Reporting suspected adverse drug reactions to the MHRA.
• Discontinuation of treatment, (or transfer if appropriate).
b) Conditions of assuming responsibility by the GP
• Satisfactory initiation, titration to optimum dosage, and response to
treatment by Consultant/ Specialist Team
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• Communication of satisfactory baseline physical checks from
Consultant/ Specialist Team to GP
• Follow up at 6 monthly intervals and monitoring of progress and
response to medication by the Consultant/ Specialist Team. Where
the Consultant/ Specialist Team amend the dose the GP will be
c) Aspects of care for which the GP is responsible
• Replying to request for shared care as soon as possible.
• Continued prescribing of melatonin in the community under guidance of
Consultant/ Specialist Team at the dose requested.
• Referring back to the Consultant/ Specialist Team for queries
regarding treatment / side effects, and concerns about compliance or
suspected drug misuse.
• Stopping treatment on the advice of the Consultant/ Specialist
• Continuation without Specialist review is not recommended.
• Reporting noted adverse events to the Consultant/ Specialist
Team and CSM.
6. Summary of cautions, contra indications, side-effects
• Patients with epilepsy (see under side effects).
• Lactose intolerance.
• May exacerbate asthma in short term.
• Pregnancy or breastfeeding.
• Patients taking monoamine oxidase inhibitors.
• Patients with severe allergies, autoimmune diseases or immune system
cancers, or taking immunosuppressants. Melatonin has been shown to
have an effect on the immune system and both enhanced immune
response and immunosuppression have been noted.
• Melatonin is generally well tolerated but long term side effects have not
• Mild headaches are the most common side effect.
• Other CNS effects reported include: dizziness, increased irritability,
altered sleep patterns, restlessness and confusion.
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• Increased seizure activity has been reported in patients with epilepsy but
there is also anecdotal evidence that seizure activity improves as a result
of improved sleep.
• Nausea, tachycardia and pruritis have been reported rarely.
• Antiplatelet drugs
• Antidiabetic agents
• CNS depressants
Please also check the latest list of interactions contained within the current
edition of the British National Formulary (BNF)
7. Special considerations
• Handover for shared care largely by written agreement. Individual
consideration of patients to occur when issues of tolerance, inconsistent
response to treatment, pre-existing medical conditions or issues of
• Obtaining melatonin may take up to 14 days. Therefore patients/carers
should request repeat prescription from their GP in advance
8. Back-up care available to GP from Hospital, including emergency contact
procedures and help line numbers
• Written correspondence following Consultant/ Specialist Team
appointments, specifically detailing the next review date and any dose
• Telephone advice/ information from the Consultant / Specialist Team
during office hours, and plans for earlier review by team if necessary.
• Out of hours on call/ emergency service contactable through hospital
9. Statement of agreement
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• Shared care is an agreement between the GP and the Consultant. This
Shared Care Guideline is a request by the consultant to share the
suggested care pathway of your patient.
• If you are unable to agree to the sharing of care and initiating the
suggested medication, please make this known to the consultant within
14 days, ideally stating the nature of your concern.
10. Written information provided to the patient
• Melatonin patient information leaflet
• Unlicensed medication information leaflet
• ‘Proforma letter of Special Clinical Need’, if appropriate
11. Supporting References
• The Maudsley: Prescribing guidelines (9th Edition) 2007. Informa
• Medicines For Children 2003. Royal College of Paediatrics and Child
• BNF for Children 2008.
• Summary of Product Characteristics. www.medicines.org.uk
• Drug procurement advice: Restrictions on the import of unlicensed
Melatonin products following the grant of a marketing authorisation for
Circadin® 2mg tablets. MHRA. August 2008
• UKMI- London New Drugs Group. APC/DTC Briefing. September 2008
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