Summary
Ramelteon has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Insomnia / Sleep Disorders would be drug repurposing rather than first-in-human development. This does not mean it is approved for Insomnia / Sleep Disorders. ClinicalTrials.gov lists 8 registered trials linking Ramelteon to Insomnia / Sleep Disorders: 8 have completed. The most advanced is Phase 4 (NCT00414102). The largest enrolment is 3339 participants (NCT02058992). Registration activity spans 2002 to 2017. The literature layer holds 18 publications for this pair: 5 Cochrane reviews, 4 meta-analyses, 1 systematic review, 3 randomised controlled trial publications and 5 clinical trial publications. Publication years run from 2011 to 2025. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Insomnia ranks 317 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Acute insomnia (<3 months): 50-60% resolve spontaneously; chronic insomnia: only 20-25% spontaneous remission at 1 year; persistent insomnia in 50-75% without treatment.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 80.0 (trials 30.0, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 8 completed, 0 other |
| Linked publications | 18 (5 Cochrane reviews, 5 clinical trial publications, 4 meta-analyses, 3 randomised controlled trial publications, 1 systematic review) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT02156271 | Mechanisms of Sleep Latency and Health: The Effect of a Melatonin Receptor Agonist in Inflammation and Insulin Resistance 2007 | completed | Phase 4 | 75 |
| NCT02669082 | The Exploratory Study to Investigate the Effect of Ramelteon for Insomnia Patients With Major Depressive Disorder by Using Actigraphy 2017 | completed | Phase 4 | 26 |
| NCT00414102 | Subjective Efficacy of Ramelteon on Sleep in Adults With Chronic Insomnia. 2006 | completed | Phase 4 | 552 |
| NCT00671294 | Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia. 2002 | completed | Phase 3 | 100 |
| NCT00671255 | Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia 2002 | completed | Phase 3 | 829 |
| NCT00755495 | Safety and Efficacy of Ramelteon and Doxepin in Subjects With Chronic Insomnia 2006 | completed | Phase 2 | 472 |
| NCT02153086 | Ramelteon 8 mg Tablets Specified Drug-use Survey: <Long-term Survey on Insomnia Accompanied by Difficulty Falling Asleep> - Transitional Survey From the Preceding Drug-use Survey - 2011 | completed | Not applicable | 236 |
| NCT02058992 | Ramelteon Tablets 8mg Drug Use Surveillance: Survey on Insomnia Associated With Sleep-onset Difficulty 2010 | completed | Not applicable | 3,339 |
Published literature
- Meta-analysis Efficacy and safety of each class of sleep medication for major depressive disorder with insomnia symptoms: A systematic review and meta-analysis of double-blind randomized controlled trialsMaruki T, Takeshima M, Yoshizawa K et al. · Psychiatry and clinical neurosciences · 2025 · PMID 40110890
- Systematic review Z-drug abuse and dependence: clinical guideline of the Brazilian Academy of Neurology for diagnosis and managementStelzer FG, Bacelar A, Éckeli AL et al. · Arquivos de neuro-psiquiatria · 2025 · PMID 41187937
- Clinical trial publication Efficacy and Safety of Transitioning to Lemborexant from Z-drug, Suvorexant, and Ramelteon in Japanese Insomnia Patients: An Open-label, Multicenter StudyOzone M, Hirota S, Ariyoshi Y et al. · Advances in therapy · 2024 · PMID 38460107
- Meta-analysis Residual effects of medications for sleep disorders on driving performance: A systematic review and network meta-analysis of randomized controlled trials: NMA driving and hypnoticsFornaro M, Caiazza C, Rossano F et al. · European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2024 · PMID 38401406
- Meta-analysis Efficacy of melatonin and ramelteon for the acute and long-term management of insomnia disorder in adults: A systematic review and meta-analysisMaruani J, Reynaud E, Chambe J et al. · Journal of sleep research · 2023 · PMID 37434463
- Cochrane review Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysisDe Crescenzo F, D'Alò GL, Ostinelli EG et al. · Lancet (London, England) · 2022 · PMID 35843245
- Clinical trial publication Lemborexant for the Treatment of Insomnia: Direct and Indirect Comparisons With Other Hypnotics Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or HarmedCitrome L, Juday T, Frech F et al. · The Journal of clinical psychiatry · 2021 · PMID 34077032
- Meta-analysis Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysisMcElroy H, O'Leary B, Adena M et al. · Journal of managed care & specialty pharmacy · 2021 · PMID 34121443
- Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacyZheng X, He Y, Yin F et al. · Sleep medicine · 2020 · PMID 32544795
- Cochrane review Efficacy and safety of non-benzodiazepine and non-Z-drug hypnotic medication for insomnia in older people: a systematic literature reviewSys J, Van Cleynenbreugel S, Deschodt M et al. · European journal of clinical pharmacology · 2020 · PMID 31838549
- Cochrane review The efficacy of melatonin and melatonin agonists in insomnia - An umbrella reviewLow TL, Choo FN, Tan SM · Journal of psychiatric research · 2020 · PMID 31715492
- Clinical trial publication Addition of Suvorexant to Ramelteon Therapy for Improved Sleep Quality with Reduced Delirium Risk in Acute Stroke PatientsKawada K, Ohta T, Tanaka K et al. · Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2019 · PMID 30322756
- Clinical trial publication The Effect of Ramelteon on Heartburn Symptoms of Patients With Gastroesophageal Reflux Disease and Chronic Insomnia: A Pilot StudyJha LK, Fass R, Gadam R et al. · Journal of clinical gastroenterology · 2016 · PMID 25887111
- Clinical trial publication [Treatment with ramelteon for sleep disturbance in severely disabled children and young adults]Miyamoto A, Fukuda I, Tanaka H et al. · No to hattatsu = Brain and development · 2013 · PMID 24313003
- Randomized controlled trial A double-blind, randomized, placebo-controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorderNorris ER, Karen Burke, Correll JR et al. · Journal of affective disorders · 2013 · PMID 22963894
- Cochrane review Ramelteon in the treatment of chronic insomnia: systematic review and meta-analysisLiu J, Wang LN · International journal of clinical practice · 2012 · PMID 22897464
- Randomized controlled trial Efficacy and tolerability of ramelteon in a double-blind, placebo-controlled, crossover study in Japanese patients with chronic primary insomniaKohsaka M, Kanemura T, Taniguchi M et al. · Expert review of neurotherapeutics · 2011 · PMID 21955196
- Randomized controlled trial Use of a post-sleep questionnaire-interactive voice response system (PSQ-IVRS) to evaluate the subjective sleep effects of ramelteon in adults with chronic insomniaWang-Weigand S, Watissée M, Roth T · Sleep medicine · 2011 · PMID 21925941
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Ramelteon approved for Insomnia / Sleep Disorders?
Ramelteon has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Insomnia / Sleep Disorders would be drug repurposing rather than first-in-human development. This does not mean it is approved for Insomnia / Sleep Disorders. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Ramelteon in clinical trials for Insomnia / Sleep Disorders?
ClinicalTrials.gov lists 8 registered trials linking Ramelteon to Insomnia / Sleep Disorders: 8 have completed. The most advanced is Phase 4 (NCT00414102). The largest enrolment is 3339 participants (NCT02058992). Registration activity spans 2002 to 2017.
What does the evidence show for Ramelteon in Insomnia / Sleep Disorders?
Ramelteon has both completed registered trials and synthesis-level publications linked to Insomnia / Sleep Disorders. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.