Summary
Diphenhydramine Hydrochloride 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 Diphenhydramine Hydrochloride to Insomnia / Sleep Disorders: 1 is currently recruiting; 1 is active or not yet recruiting; 4 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT07542756). It plans or enrolled 1200 participants. Registration activity spans 2010 to 2026. The literature layer holds 1 publication for this pair: 1 clinical trial publication. The dated items are from 1990. These are primary trial reports rather than syntheses, so results have not yet been pooled or graded independently.
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 | 52.0 (trials 30.0, literature 2.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 1 recruiting, 1 active / not yet recruiting, 4 completed, 2 other |
| Linked publications | 1 (1 clinical trial publication) |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT03968939 | Total Joint Arthroplasty and Sleep 2019 | completed | Phase 4 | 55 |
| NCT02578186 | Evaluation of Diphenhydramine Hydrochloride Effects in Subjects With Occasional Sleeplessness 2013 | completed | Phase 4 | 33 |
| NCT07542756 | A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia 2026 | recruiting | Phase 4 | 1,200 |
| NCT03331042 | SM-1 vs 2 Comparators and Placebo in Participants With a History of Transient Insomnia. 2017 | completed | Phase 3 | 85 |
| NCT01100645 | Efficacy and Safety of the Herbal Medicine Sominex ® (Passiflora Incarnata L., Valeriana Officinalis L. and Crataegus Oxyacantha L.), Manufactured by the Laboratory EMS S / A in Patients With Psychophysiological Insomnia 2010 | status unknown | Phase 3 | 100 |
| NCT03338764 | An Investigational Study to Assess Efficacy and Pattern of Use of SM-1 in Subjects With a History of Transient Insomnia 2023 | withdrawn | Phase 3 | — |
| NCT02671760 | Pilot Study of a Combination Drug Product for Treatment of Short-term Insomnia 2016 | completed | Phase 2 | 39 |
| NCT04396327 | SM-1 vs. an Active Comparator in A Model of Transient Insomnia 2020 | not yet recruiting | Phase 2 | 14 |
Published literature
- Clinical trial publication Clinical evaluation of diphenhydramine hydrochloride for the treatment of insomnia in psychiatric patients: a double-blind studyKudo Y, Kurihara M · Journal of clinical pharmacology · 1990 · PMID 2243152
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 Diphenhydramine Hydrochloride approved for Insomnia / Sleep Disorders?
Diphenhydramine Hydrochloride 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 Diphenhydramine Hydrochloride in clinical trials for Insomnia / Sleep Disorders?
ClinicalTrials.gov lists 8 registered trials linking Diphenhydramine Hydrochloride to Insomnia / Sleep Disorders: 1 is currently recruiting; 1 is active or not yet recruiting; 4 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT07542756). It plans or enrolled 1200 participants. Registration activity spans 2010 to 2026.
What does the evidence show for Diphenhydramine Hydrochloride in Insomnia / Sleep Disorders?
Diphenhydramine Hydrochloride has 4 completed trials and 1 linked publication for Insomnia / Sleep Disorders. Completed trials may or may not have posted results; follow the NCT links to check. 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.