Based on a trial that showed melatonin improved total sleep time in children with ADHD and sleep onset insomnia, Colonis’ Melatonin 1mg/ml Oral Solution was approved by the MHRA in the United Kingdom.
According to a recent announcement, the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted a label extension to Clinigen’s melatonin 1mg/ml oral solution for the short-term treatment of jet lag in adults and sleep onset insomnia in children and adolescents between the age of 6 and 17 years with attention-deficit hyperactivity disorder (ADHD).1
Findings from a trial featuring 105 children, aged 6 to 12 years old, showed that melatonin enhanced sleep duration in children with ADHD and sleep onset insomnia.1,2 The findings demonstrated that with the use of melatonin, children with ADHD and sleep onset insomnia may decrease sleep latency and increase sleep efficiency.
The children with sleep onset insomnia advanced with the dim light melatonin by 26.9 (±47.8) minutes, on the other hand, the placebo had a delay of 10.5 (±37.4 minutes; P <.0001).1 The melatonin onset group had an advance of 44.4 (±67.9) minutes whereas the placebo had a delay of 12.8 (±60.0 minutes; P < .0001). Treatment with melatonin increased the total time asleep, which was 19.8 (±61.9) minutes for the children, in comparison with those on placebo, who decreased by –13.6 (±50.6) minutes (P = .01).
“We welcome the MHRA’s approval for a condition that negatively affects the quality of life for children and adolescents diagnosed with ADHD and increases the burden for support networks,” Henno Welgemoed, Director of Medical Affairs at Colonis said in a statement.2
The randomized, double-blind, placebo-controlled study spanned 4 weeks. 1 Patients were assigned to either 3 or 6 mg melatonin (depending on body weight), or placebo. The primary outcomes were sleep onset, total time asleep, and salivary dim light melatonin onset, which were actigraphy-derived. Results showed that the sleep log item mean score for difficulty falling asleep decreased by 1.2 (±1.3) points with melatonin and by 0.1 (±0.8) points with placebo (P <.0001).1
Lead investigator, Kristiaan van der Heijden, PhD, associate professor, Leiden University, and colleagues noted, “Melatonin improved objective sleep onset and sleep duration, reduced subjective difficulty falling asleep, and induced advances of sleep onset of greater than 30 minutes in about half of the melatonin-treated children.” The melatonin did not demonstrate an effect on the children's cognitive performance, behavior, and quality of life.1
“This approval provides a valuable treatment option for children and adolescents suffering with ADHD and sleep onset insomnia, adding further breadth to Colonis’ growing paediatric portfolio while supporting Clinigen Group’s mission to deliver the right medicine to the right patient at the right time,” Welgemoed said in a statement.2
Other findings from the trial included the interdaily stability of sleep-wake rhythm, which ranged between 0.65 to 0.64 and was similar to the 0.63 which was displayed previously in children with ADHD who did not have insomnia. Although it was slightly lower than in children without ADHD or insomnia (unpublished results; 0.68 ± 0.13; n = 9;).1,5
One of the limitations of the study was a large number of missing data for some of the measures for behavior and quality of life, as well as a small risk of reporter bias since the missing data amount was the same for both of the treatment groups. Another limitation was that the results may not be relevant to stimulant-treated children with ADHD since findings suggest deteriorated sleep may be the effect from the stimulant treatment.3,4
Van der Heijden et al noted, “we recommend that melatonin treatment be prescribed only when complaints of insomnia are persistent and severe and impose a burden on the individual child, if possible after amelioration of possible underlying extrinsic factors and preferably in those children demonstrating a delayed onset of endogenous melatonin rhythm.”