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Melatonin is currently an unlicensed, “named patient only” medicine in the UK, although it is available as a dietary supplement in the United States and over the internet. It is used for a variety of sleep disorders in children who often have neurodevelopmental impairments.1,2 There remains a dearth of robust randomised controlled trials to demonstrate its efficacy, while lack of pharmacokinetic, pharmacodynamics, and toxicology data limits knowledge of therapeutic dose ranges, formulations, and adverse effects.
We carried out an anonymous questionnaire survey to examine prescribing practices of members of the British Association for Community Child Health (BACCH) and the British Academy of Childhood Disability (BACD) (see ADCwebsite: http://www.archdischild.com/supplemental).
From a newsletter circulation reaching an estimated 926 paediatricians, responses to the questionnaire were received from 148 (about 15%) (table 1).
Of these 98% were currently prescribing, or had prescribed melatonin in the last year; data on a total of 1918 children were obtained.
The dose prescribed (0.5–24 mg) varied widely (table 2).
Autism (68%) and attention deficit hyperactivity disorder (44%) were the most frequent clinical diagnoses in the children prescribed melatonin. On a crude four point scale of perceived effectiveness (never, rarely, usually, always), over 95% of respondents found melatonin “usually” or “always” effective. Adverse events were reported by 18% (n = 27) of respondents including: new onset seizure activity (n = 2), increased seizure frequency (n = 3), hyperactivity (n = 5), agitation/behavioural changes (n = 6), worsening sleep pattern (n = 6), nightmares (n = 2), and constipation (n = 2).
As this survey was opportunistic, and unfunded, we did not have the opportunity to further interrogate the non-responders and determine to what extent they systematically differed from the responders. Information on frequency of prescribing is also missing on a national level, as exact numbers of melatonin prescriptions are not recorded, but since November 2002, 239 UK hospitals/trust pharmacies have requested melatonin (personal communication, Peter Stephens, IMSHealth, 2004).
Reports of adverse events from our study mirror those in the literature.2–4 Although 27 respondents in this limited survey reported adverse events, only 13 reports, involving 25 adverse events were notified to the UK Medicines and Healthcare products Regulatory Agency (MHRA) (Committee for Safety of Medicines, Drug Analysis Print: Melatonin; personal communication, 2004) and two notified to the UK Food Standards Agency in the same period (personnel communication, Cath Mulholland, 2004). Whether these “adverse events” represent a significant rise above events that would be seen by chance in this population will need much larger studies over a longer time period.
It remains crucial to establish just how effective melatonin is for children with developmental disorders, through large scale, multicentre randomised controlled trials. This survey suggests that problems agreeing appropriate and safe dose ranges, the heterogeneity of underlying developmental problems, and a potentially wide range of underlying sleep disorders are just a few of the hurdles that will need to be overcome.
The authors would like to acknowledge the help of Ms Cath Mulholland (Food Standards Agency) for data concerning adverse events reporting in the UK and Mr Peter Stephens (IMSHealth) for NHS prescribing data.
Competing interests: none declared