Summary
Mirtazapine 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 Mirtazapine to Insomnia / Sleep Disorders: 2 are active or not yet recruiting; 6 have completed. The most advanced is Phase 4 (NCT05978219). The largest enrolment is 538 participants (NCT00561821). Registration activity spans 2006 to 2025. The literature layer holds 12 publications for this pair: 3 Cochrane reviews, 3 meta-analyses, 1 systematic review and 5 clinical trial publications. Publication years run from 2012 to 2026. 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, 2 active / not yet recruiting, 6 completed, 0 other |
| Linked publications | 12 (5 clinical trial publications, 3 Cochrane reviews, 3 meta-analyses, 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT05978219 | Efficacy of Mirtazapine in Major Depressive Disorder With Insomnia 2023 | completed | Phase 4 | 135 |
| NCT00561821 | Efficacy and Safety Study of Org 50081 (Esmirtazapine) in Elderly Participants (P05709) 2007 | completed | Phase 3 | 538 |
| NCT00631657 | A 6-Month Efficacy and Safety Study of Org 50081 in Adult Patients With Chronic Primary Insomnia (21106/P05701/MK-8265-002) 2008 | completed | Phase 3 | 460 |
| NCT00561574 | A Long-Term Safety Study of Org 50081 (Esmirtazapine) in Elderly Outpatients With Chronic Primary Insomnia (176005/P05697/MK-8265-001) 2008 | completed | Phase 3 | 259 |
| NCT00482612 | Study of the Safety and Effectiveness of Esmirtazapine in Participants With Chronic Primary Insomnia (P05706) 2006 | completed | Phase 3 | 526 |
| NCT00488072 | Effects of Mirtazapine on Appetite in Advanced Cancer Patients 2007 | active, not recruiting | Phase 2 | 98 |
| NCT05247697 | Mirtazapine for Chronic Insomnia in Older Adults 2022 | completed | Phase 1 | 60 |
| NCT06443242 | Efficacy and Safety of Low-dose Laser Acupuncture on Treating Insomnia Associated With Major Depressive Disorder 2025 | not yet recruiting | Not applicable | 120 |
Published literature
- Cochrane review Management of insomnia symptoms in depressed patients treated with agomelatine, mirtazapine and trazodone: A systematic review and meta-analysisZhang X, Chen Y, Deng R et al. · Journal of affective disorders · 2026 · PMID 41679391
- Clinical trial publication Mirtazapine for chronic insomnia in older adults: a randomised double-blind placebo-controlled trial-the MIRAGE studyNguyen PV, Dang-Vu TT, Forest G et al. · Age and ageing · 2025 · PMID 40135470
- Clinical trial publication Effectiveness of low-dose amitriptyline and mirtazapine in patients with insomnia disorder and sleep maintenance problems: a randomised, double-blind, placebo-controlled trial in general practice (DREAMING)Bakker MH, Hugtenburg JG, Bet PM et al. · The British journal of general practice : the journal of the Royal College of General Practitioners · 2025 · PMID 39814428
- Cochrane review Efficacy and safety of eszopiclone combined with drug therapy in the treatment of insomnia after stroke: A network meta-analysis and systematic reviewLi RY, Zhu DL, Chen KY · PloS one · 2024 · PMID 38315683
- Meta-analysis Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysisLappas AS, Glarou E, Polyzopoulou ZA et al. · Sleep medicine · 2024 · PMID 38795401
- 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
- Clinical trial publication A Pilot Crossover Trial of Sleep Medications for Sleep-disturbed Methadone Maintenance PatientsStein MD, Kurth ME, Anderson BJ et al. · Journal of addiction medicine · 2020 · PMID 30870203
- Systematic review Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disordersSilvestri R, Aricò I, Bonanni E et al. · Maturitas · 2019 · PMID 31547910
- Clinical trial publication Low doses of mirtazapine or quetiapine for transient insomnia: A randomised, double-blind, cross-over, placebo-controlled trialKarsten J, Hagenauw LA, Kamphuis J et al. · Journal of psychopharmacology (Oxford, England) · 2017 · PMID 28093029
- Clinical trial publication A Phase 2 Randomized Dose-Finding Study With Esmirtazapine in Patients With Primary InsomniaRuwe F, IJzerman-Boon P, Roth T et al. · Journal of clinical psychopharmacology · 2016 · PMID 27482970
- Meta-analysis Insomnia and somnolence associated with second-generation antidepressants during the treatment of major depression: a meta-analysisAlberti S, Chiesa A, Andrisano C et al. · Journal of clinical psychopharmacology · 2015 · PMID 25874915
- Cochrane review Comparative effectiveness of second-generation antidepressants for accompanying anxiety, insomnia, and pain in depressed patients: a systematic reviewThaler KJ, Morgan LC, Van Noord M et al. · Depression and anxiety · 2012 · PMID 22553134
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 Mirtazapine approved for Insomnia / Sleep Disorders?
Mirtazapine 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 Mirtazapine in clinical trials for Insomnia / Sleep Disorders?
ClinicalTrials.gov lists 8 registered trials linking Mirtazapine to Insomnia / Sleep Disorders: 2 are active or not yet recruiting; 6 have completed. The most advanced is Phase 4 (NCT05978219). The largest enrolment is 538 participants (NCT00561821). Registration activity spans 2006 to 2025.
What does the evidence show for Mirtazapine in Insomnia / Sleep Disorders?
Mirtazapine 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.