Melatonin (1) – Slenyto®

Children and adolescents aged 2–18 years with sleep disorders associated with autism spectrum disorder (ASD) and/or Smith-Magenis syndrome, where sleep hygiene measures have proved insufficient

• Hint of a minor additional benefit.
• Overall, there is a hint of a minor additional benefit.
• The certainty of the findings must be regarded as limited due to several factors.
• Due to these uncertainties, the certainty of the evidence is classified as a hint.
• mortality
  • No patients died during the study.
• Morbidity – total sleep duration
  • A statistically significant increase in sleep duration (32.32 min) and a statistically significant reduction in sleep latency (25.20 min) were observed.
  • The extent of the improvement in these sleep-related endpoints is considered to be minor.
  • However, the clinical relevance of the observed changes remains unclear.
• Morbidity – sleep latency
  • Both a statistically significant increase in sleep duration (32.32 min) and a statistically significant reduction in sleep latency (25.20 min) were observed.
  • The extent of the improvement in these sleep-related endpoints is considered to be minor.
  • However, the clinical relevance of the observed changes remains unclear.
• Morbidity – Composite Sleep Disturbance Index (CSDI)
  • However, due to the insufficiently demonstrated validity of the instrument in the therapeutic indication, it cannot be taken into account for the derivation of an additional benefit.
  • Overall, therefore, no relevant data on sleep quality are available.
• Morbidity – emotional functioning and behavioural functioning
  • Emotional and behavioural functioning were assessed using the Children’s Global Assessment Scale (CGAS).
  • In the present indication, the CGAS is regarded as validated; however, it should be noted that the pharmaceutical manufacturer uses a modified and non-validated version in which emotional functioning and behavioural functioning were assessed instead of general functioning.
  • No statistically significant differences were observed between the treatment groups.
• Morbidity – behavioural strengths and difficulties (Strength and Difficulties Questionnaire, SDQ)
  • Behavioural strengths and difficulties were assessed using the Strength and Difficulties Questionnaire (SDQ).
  • No statistically significant difference was observed between the treatment arms, either for the SDQ factors or for the impact score.
• health-related quality of life
  • No data were collected on the endpoint of health-related quality of life in the NEU-CH-7911 study.
• Side effects
  • For the endpoints of SAE and discontinuation due to AEs, no statistically significant difference was observed between the treatment arms in either case.
  • A statistically significant difference to the detriment of melatonin compared with BSC/placebo was observed for the AE of somnolence (28.3% vs. 12.3%, p=0.027).
  • In the overall assessment, this result does not lead to a downgrading of the additional benefit.
• Overall assessment
  • No difference was observed between the treatment groups for the endpoint of mortality, as no deaths occurred.
  • For the endpoints total sleep duration and sleep latency, statistically significant differences were found in favour of melatonin compared with BSC; however, their clinical relevance cannot be conclusively assessed and their extent is considered to be minor.
  • Health-related quality of life was not investigated in the studies.
  • In the category of side effects, no statistically significant difference between the treatment groups was observed in the overall rates (AEs, SAE and therapy discontinuations due to AEs).
  • Based on the study results, an advantage for melatonin over BSC can be inferred in the morbidity category for children and adolescents aged 2–18 years with sleep disorders associated with autism spectrum disorder (ASD) and/or Smith-Magenis syndrome, when sleep hygiene measures have proved insufficient.

Courtesy translation only, please refer to the German original.