The Pharmacokinetics, Dosage, Preparation Forms, and Efficacy of Orally Administered Melatonin for Non-Organic Sleep Disorders in Autism Spectrum Disorder During Childhood and Adolescence: A Systematic Review
Bibliographic record
Abstract
Background: To date, it remains unclear which oral doses and preparation forms of melatonin should be recommended for children and adolescents with non-organic sleep disorders and autism spectrum disorder (ASD). We reviewed the current state of knowledge on this topic based on randomised placebo-controlled trials (RCTs) and diagnosis-related blood melatonin concentrations available in this age group. Method: Two investigators independently searched PubMed, PsycINFO, MEDLINE, and Cochrane CENTRAL on 1 March 2025 for the keywords “melatonin”, “autism”, and “randomised” in titles and abstracts in all languages, including an evaluation of the references of the reviews, systematic reviews, and meta-analyses published up to that date, some of which were based on searches in numerous databases. Based on this, additional in-depth searches were carried out in PubMed for pharmacokinetic, physiological, and pathophysiological data on melatonin in children and adolescents, with a special focus on ASD. Results: To date, five RCTs on non-organic sleep disorders in children and adolescents with the sole diagnosis of ASD or with subgroup analyses in the presence of several initial diagnoses such as ADHD, epilepsy, Smith–Magenis, or Fragile X syndrome are available. In these studies, rapid-release, non-delayed preparations were administered orally. In one of these studies, the clinical efficacy of a combination preparation with a sustained-release and a non-released active substance component was tested. Pharmacokinetic data with multiple determinations of melatonin concentrations in the blood are only available for children with ASD in the form of a case series (N = 9). Discussion: RCTs comparing the efficacy of delayed melatonin preparations with non-delayed rapid-release oral preparations are not yet available. Physiological data and clinical effects documented in five RCTs indicate that non-delayed melatonin preparations with an initial rapid onset of action are effective for non-organic sleep disorders in children and adolescents with ASD. Conclusions: From a clinical, pharmacokinetic, and physiological point of view, the RCTs available to date and the data on melatonin concentrations in the blood of children with ASD, measured several times over 24 h, suggest that a low oral melatonin dose and a non-delayed preparation with rapid onset should be started in children and adolescents with non-organic sleep disorders in ASD, if sleep hygiene advice and psychotherapeutic interventions have not demonstrated sufficient effects.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.019 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.009 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".