Evidence to support the Joint Formulary Group (JFG)- Uses of Melatonin

The Medicines Optimisation team at NHS Bristol, North Somerset, and South Gloucestershire ICB coordinate the Joint Formulary Group (JFG). The JFG includes representatives from primary and secondary care covering all prescribing across Bristol, North Somerset and South Gloucestershire.

The Joint Formulary sets the requirements for cost-effective prescribing in the locality. Any drug not listed in the Formulary is considered to be Non-Formulary and is not to be routinely prescribed. Please see the Bristol, North Somerset and South Gloucestershire Joint Formulary website for more information.

The ICB Clinical Effectiveness team were asked to support the JFG in response to applications made for three different indications for melatonin. The applications were for use as follows:

Melatonin for treating sleep disorders in adult patients with dementia once physical/psychological causes are ruled out, and sleep hygiene measures have failed
Melatonin for aiding the onset of sleep in children in a Paediatric Intensive Care Unit (PICU) or Paediatric High Dependency Unit (PHDU) when sleep hygiene measures have failed
Melatonin for treating sleep disorders in patients with Attention Deficit Hyperactivity Disorder (ADHD), Learning Disability (LD), and/ or Autistic Spectrum Disorder (ASD) once physical/psychological causes are ruled out, and sleep hygiene measures have failed.

Clinical Effectiveness Team’s Input

The ICB Clinical Effectiveness (CE) team undertook three evidence reviews, one for each of the proposed melatonin uses listed above to support the JFG’s decision-making.

In these evidence reviews, as far as possible, the following points were addressed to aid discussion in the JFG:

Quality and strength of the evidence
Patient safety
Efficacy and clinical effectiveness
Cost-effectiveness and resource impact.

Impact of ‘Melatonin for sleep outcomes in dementia’

The evidence review demonstrated a paucity of good quality research evidence examining the use of melatonin for sleep outcomes in dementia. The available evidence focussed predominantly on Alzheimer’s Disease rather than other types of dementia.

The outcome of the JFG discussion about this use of melatonin was that, based on a lack of evidence, it would not be added to the formulary at this time. However, considering the dearth of studies examining this indication yet the considerable anecdotal evidence of benefit, where it had been used ‘off-formulary’ in Bristol, North Somerset and South Gloucestershire, a local study was commissioned to develop an evidence base for the area.

The results of this study will inform decision-making for future JFG applications for the use of melatonin in treating sleep disorders in adult patients with dementia.

As a decision was reached and ratified shortly after the JFG meeting, this evidence review was considered appropriate for sharing on the WEAHSN Evidence Repository.

Impact of ‘Melatonin for sleep outcomes on PICU/PHDU’

The evidence review demonstrated a notable lack of evidence on the effectiveness of the use of melatonin in PICU and PHDU environments. However, there was evidence that melatonin has a good safety profile in paediatric populations and may be beneficial for sleep outcomes in children more broadly.

Furthermore, there was evidence that ‘off-formulary’ prescriptions for melatonin in PICU/PHDU were increasing internationally.

The outcome of the JFG discussion about this use of melatonin was that given the safety profile of melatonin use with paediatrics and the short-term duration of melatonin administration (i.e., only whilst the child is on PICU/PHDU), it would be added to the formulary. There is an expectation that being used ‘on-formulary’ will enable better local data collection on the use of melatonin for this purpose.

As a decision was reached and ratified shortly after the JFG meeting, this evidence review was considered appropriate for sharing on the WEAHSN Evidence Repository.

Impact of ‘Use of melatonin for sleep outcomes in ADHD/ LD/ ASD’

The evidence review demonstrated a considerable volume of clinical evidence examining the use of melatonin for sleep outcomes in patients with ADHD, LD, and/ or ASD. However, despite this, much of the evidence was limited by variable quality due to methodological heterogeneity, populations assessed, and risk of bias.

The review showed there may be more evidence for the use of melatonin for LD and ASD, rather than ADHD.

The outcome of the JFG discussion about this use of melatonin was that it would not be added to the formulary for ADHD but may be added for LD and ASD.

Further work is required before a decision can be made about making these changes due to additional financial costs that would be incurred by the system.

Additional Reflections on Impact

When asked for their reflections on the impact of CE team support on the JFG decision process, members of the Medicines Optimisation team indicated it was very helpful to outsource the evidence reviews to the CE team for several reasons:

The independence of the CE team from the JFG decision-making process was considered to have added rigour to its assurance process by providing unbiased reviews of the evidence
The Medicine’s Optimisation team neither had the capacity nor the skill set available to conduct evidence reviews, with a sufficient level of depth and critical appraisal, to enable objective decisions about adding melatonin to the formulary for the indications listed previously
The application process can be emotive with passionate stakeholders sharing anecdotal evidence as to why they believe their formulary request should be successful. However, disinterested evidence reviews enabled the JFG to position and weigh the different forms of evidence in a more detached manner.

Since these reviews were conducted, the CE team has supported the Medicines Optimisation team with more evidence reviews to support new applications for formulary additions.