Insomnia / Sleep Disorders — RepurpOS

Disease overview

Alterations

167

Molecular (A)

100

Clinical (B–E)

Direct drugs

129

Via biomarker

191

Natural agents

Natural products

101

Merged ranked

317

With trial/literature evidence

Sources: Open Targets, HPO, ClinicalTrials.gov, DGIdb, ChEMBL, PubMed MeSH, PubMed Literature, PubMed NP · Pipeline phase 7 · Updated 2026-07-05

Remission & chronicity

Spontaneous remission

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

Best-intervention remission

Cognitive Behavioural Therapy for Insomnia (CBT-I): 70-80% response rate; 40-60% remission (normalised sleep); durable at 6-24 months post-treatment; superior to sleep medication in long-term outcomes; digital CBT-I (Sleepio, Somryst) equivalent efficacy to in-person

Drug-free remission

—

Relapse after remission

—

Chronicity

—

Gap size

Very large — CBT-I is guideline-recommended as first-line but almost universally unavailable; medication is default

Primary barrier

access/framing

Barrier detail: AASM and most sleep guidelines recommend CBT-I as first-line over medication for chronic insomnia; fewer than 1% of insomnia sufferers have access to a CBT-I trained therapist; digital CBT-I exists and works but is rarely prescribed; benzodiazepines and z-drugs continue to dominate prescribing despite guidelines against long-term use

Last SoC change: 2022 — FDA approved daridorexant (Quviviq — orexin receptor antagonist); 2019 lemborexant; 2014 suvorexant (first orexin antagonist); z-drugs (zopiclone, zolpidem) since 1990s; benzodiazepines for sleep since 1960s

Remission data layers: disease_db_100 · source-locked manual data · confidence: high

Identifiers: MONDO: MONDO:0013600 · MESH: D007319 · UMLS_CUI: C0917801

Right to Try Relevance

Eligibility: This disease meets the federal and state right-to-try legal standard (21 U.S.C. § 360bbb-0a and Montana SB 535): it lacks disease-modifying therapy with indication-specific FDA approval. Patients with Insomnia may be eligible to access investigational therapies outside of clinical trials under right-to-try frameworks.

Investigational Agents

Phase 3: 33, Phase 2: 58, Phase 1: 6

Most Advanced Phase

Phase 3

Highest dev. stage

Gene Targets

167

Actionable

Pipeline Compounds (Top 6)

Darapladib, Fenretinide, Almorexant, Amitriptyline, Brotizolam, Cannabidiol

Legal Standard: Right-to-try requires the disease lacks "adequate approved therapy for that specific disease" (not symptom-management drugs). This distinction means a disease with antidepressants available still qualifies if no FDA approval exists for THAT disease indication.

View Right-to-Try Compendium

Alterations

167 total · Types A (molecular) through E (functional)

Name	Type	Subtype	Direction	Frequency	Evidence	Sources	Links
Abnormal autonomic nervous system physiology	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Abnormal pineal melatonin secretion	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Abnormal pyramidal sign	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Abnormality of extrapyramidal motor function	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Abnormally slow thought process	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Anxiety	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Apnea	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Ataxia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Cerebral cortex with spongiform changes	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Cognitive impairment	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Constipation	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Dementia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Depression	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Diplopia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Dysarthria	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Dysphagia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
EEG with spike-wave complexes	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Emotional lability	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Epiphora	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Fever	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hallucinations	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hyperhidrosis	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hypertension	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Increased circulating cortisol level	Lab / Clinical	Lab value	—	—	Moderate	HPO, Monarch	HPO
Insomnia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Laryngeal stridor	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Loss of speech	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Myoclonus	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Neuronal loss in central nervous system	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Reduced attention regulation	Lab / Clinical	Lab value	—	—	Moderate	HPO, Monarch	HPO
Short REM sleep	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Short term memory impairment	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Sleep apnea	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Sleep-wake cycle disturbance	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Tachycardia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Thalamic hypometabolism in FDG PET	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Urinary retention	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Weight loss	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
ADCY2 adenylate cyclase 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA2A adrenoceptor alpha 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA2B adrenoceptor alpha 2B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRA2C adrenoceptor alpha 2C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
APOE apolipoprotein E	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ASPSCR1 ASPSCR1 tether for SLC2A4, UBX domain containing	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ATP2B2 ATPase plasma membrane Ca2+ transporting 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
BTBD9 BTB domain containing 9	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CA10 carbonic anhydrase 10 (inactive)	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1A calcium voltage-gated channel subunit alpha1 A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1B calcium voltage-gated channel subunit alpha1 B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1C calcium voltage-gated channel subunit alpha1 C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1D calcium voltage-gated channel subunit alpha1 D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1F calcium voltage-gated channel subunit alpha1 F	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1G calcium voltage-gated channel subunit alpha1 G	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1H calcium voltage-gated channel subunit alpha1 H	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1I calcium voltage-gated channel subunit alpha1 I	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1S calcium voltage-gated channel subunit alpha1 S	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA2D1 calcium voltage-gated channel auxiliary subunit alpha2delta 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA2D2 calcium voltage-gated channel auxiliary subunit alpha2delta 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA2D3 calcium voltage-gated channel auxiliary subunit alpha2delta 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNB1 calcium voltage-gated channel auxiliary subunit beta 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNB2 calcium voltage-gated channel auxiliary subunit beta 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNB3 calcium voltage-gated channel auxiliary subunit beta 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNB4 calcium voltage-gated channel auxiliary subunit beta 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG1 calcium voltage-gated channel auxiliary subunit gamma 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG2 calcium voltage-gated channel auxiliary subunit gamma 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG3 calcium voltage-gated channel auxiliary subunit gamma 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG4 calcium voltage-gated channel auxiliary subunit gamma 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG5 calcium voltage-gated channel auxiliary subunit gamma 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG6 calcium voltage-gated channel auxiliary subunit gamma 6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG7 calcium voltage-gated channel auxiliary subunit gamma 7	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNG8 calcium voltage-gated channel auxiliary subunit gamma 8	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CHCHD3 coiled-coil-helix-coiled-coil-helix domain containing 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CNR1 cannabinoid receptor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CSMD1 CUB and Sushi multiple domains 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Change in Anxiety symptoms	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Change in Daily function	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Change in Depression symptoms	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Change in Insomnia Severity Index (ISI)	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Change in Insomnia symptoms	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Change in Life quality	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
DAB1 DAB adaptor protein 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
DRD2 dopamine receptor D2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Depressive symptoms	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
EFNA5 ephrin A5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ELAVL2 ELAV like RNA binding protein 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Engagement with intervention method	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
FES FES proto-oncogene, tyrosine kinase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FOXP1 forkhead box P1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FOXP2 forkhead box P2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA1 gamma-aminobutyric acid type A receptor subunit alpha1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA2 gamma-aminobutyric acid type A receptor subunit alpha2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA3 gamma-aminobutyric acid type A receptor subunit alpha3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA4 gamma-aminobutyric acid type A receptor subunit alpha4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA5 gamma-aminobutyric acid type A receptor subunit alpha5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA6 gamma-aminobutyric acid type A receptor subunit alpha6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB1 gamma-aminobutyric acid type A receptor subunit beta1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB2 gamma-aminobutyric acid type A receptor subunit beta2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB3 gamma-aminobutyric acid type A receptor subunit beta3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRD gamma-aminobutyric acid type A receptor subunit delta	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRE gamma-aminobutyric acid type A receptor subunit epsilon	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRG1 gamma-aminobutyric acid type A receptor subunit gamma1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRG2 gamma-aminobutyric acid type A receptor subunit gamma2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRG3 gamma-aminobutyric acid type A receptor subunit gamma3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRP gamma-aminobutyric acid type A receptor subunit pi	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRQ gamma-aminobutyric acid type A receptor subunit theta	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GALNT2 polypeptide N-acetylgalactosaminyltransferase 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GPC6 glypican 6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Global Pain Severity-Graded Chronic Pain Scale	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
HCRTR1 hypocretin receptor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HCRTR2 hypocretin receptor 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HRH1 histamine receptor H1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR2A 5-hydroxytryptamine receptor 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HTR2C 5-hydroxytryptamine receptor 2C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
IGSF9B immunoglobulin superfamily member 9B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Inflammatory Biomarkers C-reactive Protein (CRP)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	LOINC
Insomnia Severity Index	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Insomnia severity	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Insulin Resistance (IR)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	LOINC
Interleukin 6 (IL-6)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
LINC03051 long independently transcribed non-coding RNA 3051	Molecular	Gene	—	—	Emerging	Open Targets	Ensembl Open Targets
LRRTM4 leucine rich repeat transmembrane neuronal 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
LSAMP limbic system associated membrane protein	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MDGA1 MAM domain containing glycosylphosphatidylinositol anchor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MEIS1 Meis homeobox 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MTNR1A melatonin receptor 1A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MTNR1B melatonin receptor 1B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Mean Latency to Persistent Sleep (LPS) Via Polysomnography	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
NEGR1 neuronal growth regulator 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NLGN1 neuroligin 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NPAS3 neuronal PAS domain protein 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OLFM4 olfactomedin 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PAX5 paired box 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PCDH9 protocadherin 9	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDE2A phosphodiesterase 2A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PRNP prion protein (Kanno blood group)	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PTPRD protein tyrosine phosphatase receptor type D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Perceived stress scale -10 (PSS-10)	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Pittsburgh Sleep Quality Index	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
RASGRP1 RAS guanyl releasing protein 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SALL1 spalt like transcription factor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SDK1 sidekick cell adhesion molecule 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC39A8 solute carrier family 39 member 8	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC6A2 solute carrier family 6 member 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLC6A4 solute carrier family 6 member 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SLCO3A1 solute carrier organic anion transporter family member 3A1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SNCA synuclein alpha	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SORCS3 sortilin related VPS10 domain containing receptor 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SPRY4 sprouty RTK signaling antagonist 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI)	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Sleep Quality	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Sleep efficiency	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Sleep onset latency (SOL)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
TCF4 transcription factor 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
TCF7L2 transcription factor 7 like 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
TERF1 telomeric repeat binding factor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
TET2 tet methylcytosine dioxygenase 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
TEX29 testis expressed 29	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
TMEM106B transmembrane protein 106B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Time in bed	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Tinnitus Handicap Inventory (THI)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Total sleep time	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Trait Anxiety Scale (TAS)	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
UGT1A1 UDP glucuronosyltransferase family 1 member A1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Visual Analog Scale (VAS)	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Wake After Sleep Onset (WASO)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
subjective sleep Quality	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—

FDA-Approved Therapies

Phase 4 agents with regulatory approval for this indication

Drug Name	Mechanism	Type
ACEBUTOLOL		Gene-targeted
ACETAZOLAMIDE	None	Gene-targeted
ADUCANUMAB		Gene-targeted
AMPHETAMINE	None	Gene-targeted
APIXABAN		Gene-targeted
APOMORPHINE	inhibitor	Gene-targeted
APRACLONIDINE	agonist	Gene-targeted
APRACLONIDINE HYDROCHLORIDE	agonist	Gene-targeted
ASENAPINE		Gene-targeted
ATENOLOL		Gene-targeted
ATIPAMEZOLE	inhibitor	Gene-targeted
ATROPINE	inhibitor	Gene-targeted
BENZPHETAMINE		Gene-targeted
BEPRIDIL		Gene-targeted
BEPRIDIL HYDROCHLORIDE	blocker	Gene-targeted
BETAXOLOL		Gene-targeted
BETHANIDINE		Gene-targeted
BICALUTAMIDE	None	Gene-targeted
BISOPROLOL		Gene-targeted
BRIMONIDINE	agonist	Gene-targeted
BRIMONIDINE TARTRATE	agonist	Gene-targeted
BROMOCRIPTINE	inhibitor	Gene-targeted
BUPROPION HYDROCHLORIDE		Gene-targeted
CABERGOLINE	inhibitor	Gene-targeted
CARBACHOL	None	Gene-targeted
CARVEDILOL		Gene-targeted
CELECOXIB		Gene-targeted
CELIPROLOL	inhibitor	Gene-targeted
CHLORPROMAZINE	inhibitor	Gene-targeted
CHOLESTEROL		Gene-targeted
CHORIOGONADOTROPIN ALFA		Gene-targeted
CIPROFLOXACIN	None	Gene-targeted
CLOMIPRAMINE	None	Gene-targeted
CLONIDINE HYDROCHLORIDE	agonist; agonist	Gene-targeted
CYCLOBENZAPRINE		Gene-targeted
DARIDOREXANT HYDROCHLORIDE	None	Direct
DEBRISOQUIN		Gene-targeted
DEXMEDETOMIDINE HYDROCHLORIDE	agonist	Gene-targeted
DEXTROAMPHETAMINE SULFATE		Gene-targeted
DIAZEPAM	None	Gene-targeted
DICHLORPHENAMIDE	None	Gene-targeted
DIETHYLSTILBESTROL	None	Gene-targeted
DIPHENHYDRAMINE HYDROCHLORIDE	None	Direct
DIPIVEFRIN		Gene-targeted
DIPIVEFRIN HYDROCHLORIDE	agonist	Gene-targeted
DONANEMAB		Gene-targeted
DONEPEZIL		Gene-targeted
DOPAMINE		Gene-targeted
DOXAZOSIN MESYLATE		Gene-targeted
DOXEPIN HYDROCHLORIDE	None	Direct
DROXIDOPA	agonist	Gene-targeted
EPHEDRINE HYDROCHLORIDE	agonist	Gene-targeted
EPHEDRINE SULFATE	agonist	Gene-targeted
EPINEPHRINE	agonist; agonist	Gene-targeted
EPINEPHRINE BITARTRATE	agonist	Gene-targeted
EPIRUBICIN	None	Gene-targeted
ERGOLOID MESYLATES	inhibitor	Gene-targeted
ERGOLOID MESYLATES, USP		Gene-targeted
ERGOTAMINE TARTRATE	agonist	Gene-targeted
ESMOLOL		Gene-targeted
ESTAZOLAM	None	Direct
ESZOPICLONE	None	Direct
ETHOXZOLAMIDE	None	Gene-targeted
ETOMIDATE		Gene-targeted
FENOFIBRATE MICRONIZED		Gene-targeted
FENOLDOPAM		Gene-targeted
FLUMAZENIL	None	Gene-targeted
FLURAZEPAM HYDROCHLORIDE	None	Direct
FLUTICASONE		Gene-targeted
FLUVASTATIN		Gene-targeted
GABAPENTIN	modulator	Gene-targeted
GABAPENTIN ENACARBIL	modulator	Gene-targeted
GALANTAMINE		Gene-targeted
GANCICLOVIR		Gene-targeted
GUANABENZ	agonist	Gene-targeted
GUANABENZ ACETATE	agonist	Gene-targeted
GUANFACINE HYDROCHLORIDE	agonist	Gene-targeted
GUANFACINE HYDROCHLORIDE	agonist	Gene-targeted
HYDROXYAMPHETAMINE HYDROBROMIDE	agonist	Gene-targeted
ILOPERIDONE		Gene-targeted
IMIPRAMINE	None	Gene-targeted
INDAPAMIDE	None	Gene-targeted
INDOMETHACIN	None	Gene-targeted
IRBESARTAN		Gene-targeted
ISOPROTERENOL		Gene-targeted
ISOSORBIDE DINITRATE	None	Gene-targeted
LABETALOL		Gene-targeted
LABETALOL HYDROCHLORIDE	inhibitor	Gene-targeted
LECANEMAB		Gene-targeted
LEMBOREXANT	None	Direct
LEVONORDEFRIN	agonist	Gene-targeted
LITHIUM CATION		Gene-targeted
LOFEXIDINE	agonist	Gene-targeted
LOFEXIDINE HYDROCHLORIDE	agonist	Gene-targeted
LORAZEPAM		Gene-targeted
LURASIDONE HYDROCHLORIDE	inhibitor	Gene-targeted
LUTEIN		Gene-targeted
MAFENIDE	None	Gene-targeted
MECAMYLAMINE	None	Gene-targeted
MELATONIN	None	Direct
MEPERIDINE HYDROCHLORIDE		Gene-targeted
MEPHENTERMINE SULFATE	agonist	Gene-targeted
METHAMPHETAMINE		Gene-targeted
METHAZOLAMIDE	None	Gene-targeted
METHOXSALEN	None	Gene-targeted
METHYLDOPA ANHYDROUS	agonist	Gene-targeted
METHYLDOPATE HYDROCHLORIDE	agonist	Gene-targeted
METOPROLOL		Gene-targeted
METOPROLOL	None	Gene-targeted
MIANSERIN	None	Gene-targeted
MILNACIPRAN		Gene-targeted
MIRTAZAPINE	inhibitor; inhibitor	Gene-targeted
MIRTAZAPINE	None	Direct
MONTELUKAST SODIUM		Gene-targeted
MOXISYLYTE	inhibitor	Gene-targeted
MOXONIDINE	agonist	Gene-targeted
NADOLOL		Gene-targeted
NALIDIXIC ACID	None	Gene-targeted
NAPHAZOLINE	agonist	Gene-targeted
NAPHAZOLINE HYDROCHLORIDE	agonist	Gene-targeted
NEBIVOLOL HYDROCHLORIDE		Gene-targeted
NICOTINE	None	Gene-targeted
NICOTINE POLACRILEX		Gene-targeted
NISOLDIPINE		Gene-targeted
NOREPINEPHRINE	agonist	Gene-targeted
NOREPINEPHRINE BITARTRATE	agonist	Gene-targeted
NORETHINDRONE ACETATE		Gene-targeted
NORFLOXACIN	None	Gene-targeted
NORTRIPTYLINE		Gene-targeted
OFLOXACIN	None	Gene-targeted
OLANZAPINE		Gene-targeted
OXYMETAZOLINE HYDROCHLORIDE	agonist	Gene-targeted
OXYMETAZOLINE HYDROCHLORIDE	agonist	Gene-targeted
PENTOBARBITAL	None	Direct
PERGOLIDE	agonist	Gene-targeted
PHENOXYBENZAMINE	inhibitor	Gene-targeted
PHENOXYBENZAMINE HYDROCHLORIDE	inhibitor	Gene-targeted
PHENTOLAMINE	inhibitor	Gene-targeted
PHENTOLAMINE MESYLATE	inhibitor	Gene-targeted
PHENYLPROPANOLAMINE		Gene-targeted
PHENYTOIN	None	Gene-targeted
PINDOLOL		Gene-targeted
PRAVASTATIN SODIUM		Gene-targeted
PRAZOSIN	inhibitor	Gene-targeted
PRAZOSIN	None	Gene-targeted
PREDNISONE		Gene-targeted
PREGABALIN	modulator	Gene-targeted
PROPRANOLOL HYDROCHLORIDE		Gene-targeted
PROPYLHEXEDRINE		Gene-targeted
PSEUDOEPHEDRINE POLISTIREX		Gene-targeted
QUAZEPAM	None	Direct
RACEPINEPHRINE	agonist	Gene-targeted
RAMELTEON	None	Direct
RAUWOLFIA SERPENTINA	inhibitor	Gene-targeted
RAUWOLFIA SERPENTINA (USP)	inhibitor	Gene-targeted
REMIFENTANIL HYDROCHLORIDE		Gene-targeted
RILMENIDINE		Gene-targeted
RISPERIDONE	inhibitor	Gene-targeted
RITONAVIR		Gene-targeted
RIVASTIGMINE		Gene-targeted
SIROLIMUS	None	Gene-targeted
SODIUM CHLORIDE		Gene-targeted
SOTALOL		Gene-targeted
SULBACTAM	None	Gene-targeted
SULOCTIDIL	blocker	Gene-targeted
SUVOREXANT	None	Direct
TACROLIMUS ANHYDROUS	None	Gene-targeted
TAZOBACTAM	None	Gene-targeted
TEMAZEPAM	None	Direct
TERODILINE HYDROCHLORIDE	blocker	Gene-targeted
TETRAHYDROZOLINE		Gene-targeted
TETRAHYDROZOLINE HYDROCHLORIDE	agonist	Gene-targeted
TIZANIDINE HYDROCHLORIDE	agonist	Gene-targeted
TIZANIDINE HYDROCHLORIDE	agonist	Gene-targeted
TOLAZOLINE	inhibitor	Gene-targeted
TOLAZOLINE HYDROCHLORIDE	inhibitor	Gene-targeted
TRAZODONE		Gene-targeted
TRETINOIN		Gene-targeted
TRIAMCINOLONE		Gene-targeted
TRIAZOLAM	None	Direct
TROGLITAZONE		Gene-targeted
TROGLITAZONE	None	Gene-targeted
XYLAZINE	agonist	Gene-targeted
XYLOMETAZOLINE	agonist	Gene-targeted
XYLOMETAZOLINE HYDROCHLORIDE	agonist	Gene-targeted
YOHIMBINE	inhibitor	Gene-targeted
ZALEPLON	None	Direct
ZOLPIDEM TARTRATE	None	Direct

Therapeutics

Direct disease associations, biomarker-linked drugs, OSMF narrative-review natural agents, and merged ranking. Only agents with registry trials or published clinical literature are shown by default.

Show agents without direct trial evidence

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
DARIDOREXANT HYDROCHLORIDE	Small molecule	Approved	Strong	100	1 trials View evidence Registry trials NCT02571855 — A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of ACT-541468 in Healthy Young Adults and Elderly Subjects (COMPLETED) PHASE1 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
DIAZEPAM	Small molecule	Approved	Strong	100	2 Cochrane 3 Meta-analysis 18 Trial pubs 10 RCT View evidence Published literature Cochrane review Auricular acupuncture treatment for insomnia: a systematic review (Journal of alternative and complementary medicine (New York, N.Y.), 2007) Cochrane review Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis (Human psychopharmacology, 2004) Meta-analysis Auricular acupuncture for insomnia: a systematic review (International journal of clinical practice, 2008) Systematic review Melatonin and melatonin agonists as treatments for benzodiazepines and hypnotics withdrawal in patients with primary insomnia. A systematic review (Drug and alcohol dependence, 2020) Clinical trial publication Masked Taper With Behavioral Intervention for Discontinuation of Benzodiazepine Receptor Agonists: A Randomized Clinical Trial (JAMA internal medicine, 2024) Clinical trial publication Therapeutic Efficacy of Head Gusha Combined with Kaitianmen in the Management of Insomnia (Alternative therapies in health and medicine, 2024) Clinical trial publication [Impacts of the repetitive transcranial acupuncture stimulation on the content of serum orexin A in patients with post-stroke insomnia] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2018) Clinical trial publication [Clinical observation of "Yinqi Guiyuan needles therapy" combined with moxibustion at Yongquan (KI 1) on perimenopausal insomnia with heart-kidney imbalance] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2018) Clinical trial publication Nefazodone in major depression: adjunctive benzodiazepine therapy and tolerability (Journal of clinical psychopharmacology, 1998) Randomized controlled trial A double-blind group comparative study using the new anti-depressant Org 3770, placebo and diazepam in patients with expected insomnia and anxiety before elective gynaecological surgery (Acta psychiatrica Scandinavica, 1985) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
DIPHENHYDRAMINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 1 Trial pubs View evidence Registry trials NCT07542756 — A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia (RECRUITING) PHASE4 NCT04396327 — SM-1 vs. an Active Comparator in A Model of Transient Insomnia (NOT_YET_RECRUITING) PHASE2 NCT03338764 — An Investigational Study to Assess Efficacy and Pattern of Use of SM-1 in Subjects With a History of Transient Insomnia (WITHDRAWN) PHASE3 NCT02671760 — Pilot Study of a Combination Drug Product for Treatment of Short-term Insomnia (COMPLETED) PHASE2 NCT03968939 — Total Joint Arthroplasty and Sleep (COMPLETED) PHASE4 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 (UNKNOWN) PHASE3 NCT03331042 — SM-1 vs 2 Comparators and Placebo in Participants With a History of Transient Insomnia. (COMPLETED) PHASE3 NCT02578186 — Evaluation of Diphenhydramine Hydrochloride Effects in Subjects With Occasional Sleeplessness (COMPLETED) PHASE4 Published literature Clinical trial publication Clinical evaluation of diphenhydramine hydrochloride for the treatment of insomnia in psychiatric patients: a double-blind study (Journal of clinical pharmacology, 1990) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
DOXEPIN HYDROCHLORIDE	Small molecule	Approved	Strong	100	5 trials View evidence Registry trials NCT07542756 — A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia (RECRUITING) PHASE4 NCT00755495 — Safety and Efficacy of Ramelteon and Doxepin in Subjects With Chronic Insomnia (COMPLETED) PHASE2 NCT07598734 — Doxepin Alone or Combined With Ramelteon Versus Placebo for Improving Sleep Quality After Primary Total Knee Arthroplasty (NOT_YET_RECRUITING) PHASE4 NCT01489982 — Treatments for Insomnia in Patients With Parkinson's Disease (COMPLETED) EARLY_PHASE1 NCT00465972 — The Treatment of Insomnia in Patients With HIV Disease (COMPLETED) PHASE4 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ESTAZOLAM	Small molecule	Approved	Strong	100	8 trials 3 Cochrane 5 Meta-analysis 43 Trial pubs 39 RCT View evidence Registry trials NCT03997058 — Observation on the Effect of Auricular Acupoint Pressing on Insomnia and Adverse Events in MHD (UNKNOWN) PHASE4 NCT00347295 — Randomised, Double-blind Study to Investigate the Safety and Efficacy of Brotizolam in Insomnia Outpatients. (COMPLETED) PHASE3 NCT00956319 — A Study to Evaluate Efficacy and Safety of Zolpidem Modified Release Formulation in Insomnia Patients (COMPLETED) PHASE4 NCT06859190 — Efficacy of Auricular Pressure Beans with Electroacupuncture and Estazolam Treating Insomnia Caused by Cancer (RECRUITING) PHASE3 NCT05452577 — Treatment of Chronic Insomnia According to Yin Yang Theory and Its Correlation With Circadian Rhythm (COMPLETED) NA NCT07306494 — Compound Ciwujia Granules in the Treatment of Insomnia (NOT_YET_RECRUITING) PHASE4 NCT06212934 — "Chou's Tiaoshen" Acupoints for Short-term Insomnia. (UNKNOWN) NA NCT06258226 — A Randomized Controlled Trial of Auricular Acupressure in Treating Estazolam-dependent Insomnia (UNKNOWN) NA Published literature Cochrane review Efficacy and safety of Chaihu plus Longgu Muli decoction combined with Estazolam in the treatment of insomnia: a meta-analysis (Sleep & breathing = Schlaf & Atmung, 2025) Cochrane review Acupuncture for cancer-related insomnia: A systematic review and meta-analysis (Phytomedicine : international journal of phytotherapy and phytopharmacology, 2022) Cochrane review Clinical effectiveness of Tui Na for insomnia compared with estazolam: A systematic review and meta-analysis of randomized controlled trials (Complementary therapies in medicine, 2019) Meta-analysis Acupuncture for Primary Insomnia: An Updated Systematic Review of Randomized Controlled Trials (Journal of alternative and complementary medicine (New York, N.Y.), 2019) Meta-analysis Auricular acupuncture for insomnia: a systematic review (International journal of clinical practice, 2008) Clinical trial publication [Clinical efficacy of acupuncture combined with estazolam on chronic insomnia] (Zhen ci yan jiu = Acupuncture research, 2026) Clinical trial publication Suanzaoren decoction improving chronic insomnia with little effects on functional connectivity within the sensorimotor network (Brain research, 2026) Clinical trial publication Altered cerebral functional activity and its associated genetic profiles underlying chronic insomnia disorder before and after treatment (The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2025) Clinical trial publication [Effects of Tiaoshu Anshen acupuncture on sleep quality and serum neurotransmitter levels in patients with chronic insomnia] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2025) Clinical trial publication [Clinical effect of the warm acupuncture of Mongolian medicine on insomnia in the elderly and its brain-gut peptide mechanism: a randomized controlled trial] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2024) Randomized controlled trial [Clinical effect of acupuncture based on syndrome differentiation in the treatment of chronic insomnia and its influence on cognitive function] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2023) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ESZOPICLONE	Small molecule	Approved	Strong	100	8 trials 10 Cochrane 18 Meta-analysis 43 Trial pubs 41 RCT View evidence Registry trials NCT06452953 — Modified Suanzaoren Decoction Versus Eszopiclone for the Treatment of Chronic Insomnia Disorder (COMPLETED) NA NCT00367965 — Study of Eszopiclone Compared to Placebo on Daytime Function in Subjects With Insomnia Related to Rheumatoid Arthritis (COMPLETED) PHASE3 NCT00247624 — Improving Sleep and Psychological Functioning in People With Depression and Insomnia (COMPLETED) PHASE4 NCT01710631 — Twelve Month Study of the Safety of Eszopiclone in Adult Subjects With Insomnia (COMPLETED) PHASE3 NCT01605253 — Eszopiclone for the Treatment of Posttraumatic Stress Disorder (COMPLETED) PHASE4 NCT07018557 — Impact of Eszopiclone on Blood Pressure in Patients With Insomnia and Hypertension (PRYSMA-HTN) (RECRUITING) PHASE4 NCT04980703 — Grain Moxibustion Treatment on Insomnia: a Randomized Controlled Trial (NOT_YET_RECRUITING) NA NCT00856973 — Safety & Efficacy Study of Study Drug (Eszopiclone) in Children and Adolescents With Attention-deficit/Hyperactivity Disorder - Associated Insomnia (COMPLETED) PHASE3 Published literature Cochrane review Comparative efficacy of positive airway pressure-based combination therapy in comorbid insomnia and sleep apnea: A systematic review and network meta-analysis (Sleep medicine reviews, 2026) Cochrane review Efficacy of auriculotherapies for primary insomnia: A systematic review and network meta-analysis (Medicine, 2026) Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review Comparative efficacy and safety of different pharmacological interventions for the treatment of depression associated with insomnia in the elderly population: a systematic review and network meta-analysis (Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society, 2025) Cochrane review Efficacy and safety of eszopiclone combined with drug therapy in the treatment of insomnia after stroke: A network meta-analysis and systematic review (PloS one, 2024) Meta-analysis Efficacy and Acceptability of Licensed and Off-Label Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness: A Systematic Review and Meta-Analysis of Randomised Trials (Acta psychiatrica Scandinavica, 2025) Systematic review Evidence-based pharmacological interventions for insomnia: a systematic review on the effects of eszopiclone on insomnia comorbid with mental disturbances (The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2026) Systematic review Z-drug abuse and dependence: clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (Arquivos de neuro-psiquiatria, 2025) Clinical trial publication [Tiaowei Jiannao acupuncture for post-ischemic stroke insomnia: a randomized controlled trial] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2025) Clinical trial publication A Mechanistic study assessing difficulty discontinuing chronic hypnotic use (Psychopharmacology, 2025) Clinical trial publication Cognitive Behavioral Therapy Alone or in Combination with Eszopiclone in Comorbid Insomnia and Obstructive Sleep Apnea in Veterans with Posttraumatic Stress Disorder: A Randomized Trial (The Psychiatric quarterly, 2025) Clinical trial publication Efficacy and Safety of Transitioning to Lemborexant from Z-drug, Suvorexant, and Ramelteon in Japanese Insomnia Patients: An Open-label, Multicenter Study (Advances in therapy, 2024) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
FLURAZEPAM HYDROCHLORIDE	Small molecule	Approved	Strong	100	6 Trial pubs 2 RCT View evidence Published literature Clinical trial publication Double-blind evaluation of temazepam, flurazepam, and placebo in geriatric insomniacs (Clinical therapeutics, 1982) Clinical trial publication Insomnia in the elderly: treatment with flurazepam hydrochloride (Journal of the American Geriatrics Society, 1979) Clinical trial publication Comparison of the hypnotic activity of triazolam, flurazepam hydrochloride, and placebo (Clinical pharmacology and therapeutics, 1975) Clinical trial publication A double-blind evaluation of a new hypnotic--flurazepam hydrochloride (South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 1973) Clinical trial publication Controlled evaluation of flurazepam hydrochloride, a new nonbarbiturate hypnotic (Military medicine, 1973) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
LEMBOREXANT	Small molecule	Approved	Strong	100	8 trials 9 Cochrane 16 Meta-analysis 25 Trial pubs 21 RCT View evidence Registry trials NCT06981195 — Effects of Lemborexant on Insomnia and Its Relationship to Mood and Behavior on Opioid Use Disorder Subjects (RECRUITING) PHASE2 NCT02350309 — Study to Evaluate the Effect of 2 Dosage Strengths of Lemborexant (E2006) on a Multiple Sleep Latency Test in Participants With Insomnia Disorder (COMPLETED) PHASE1 NCT04742699 — An Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Transitioning to Lemborexant in Japanese Subjects With Insomnia (COMPLETED) PHASE4 NCT02783729 — Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1) (COMPLETED) PHASE3 NCT05594589 — A Study to Assess the Pharmacodynamics of Lemborexant in Korean Participants With Insomnia Disorder (COMPLETED) PHASE2 NCT01463098 — A 2-Part Single Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006 (COMPLETED) PHASE1 NCT06496282 — Lemborexant on Improving Sleep Quality Among Hospital Rotating Shift Workers (RECRUITING) PHASE3 NCT05618002 — Lemborexant vs Zopiclone vs Clonidine for Insomnia Treatment in Chronic Pain Patients (RECRUITING) Published literature Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review Efficacy and safety of lemborexant in patients with insomnia: a systematic review and meta-analysis (Sleep medicine, 2025) Cochrane review Efficacy and safety of lemborexant vs placebo in treating adults with insomnia disorder: a systematic review and meta-analysis of 1976 patients (Naunyn-Schmiedeberg's archives of pharmacology, 2025) Cochrane review Orexin receptor antagonists in the treatment of insomnia associated with psychiatric disorders: a systematic review (Translational psychiatry, 2024) Cochrane review Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis (Arquivos de neuro-psiquiatria, 2023) Meta-analysis Comparative efficacy and safety of daridorexant, lemborexant, and suvorexant for insomnia: a systematic review and network meta-analysis (Translational psychiatry, 2025) Meta-analysis Comparison of efficacy and safety of dual orexin receptor antagonists lemborexant and daridorexant for the treatment of insomnia: a systematic review and meta-analysis (Psychopharmacology, 2025) Systematic review Efficacy and safety profiles of FDA-approved dual orexin receptor antagonists in depression: A systematic review of pre-clinical and clinical studies (Journal of psychiatric research, 2025) Systematic review The putative effects of orexin receptor antagonists on pain and sleep in humans: A systematic review (Sleep medicine, 2025) Clinical trial publication A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial of lemborexant in adults with insomnia disorder (Sleep medicine, 2026) Clinical trial publication Effect of lemborexant on sleep parameters and architecture in adult and elderly participants with mild-to-severe obstructive sleep apnea (Sleep medicine, 2025) Clinical trial publication Effect of lemborexant on sleep architecture in participants with insomnia disorder and mild obstructive sleep apnea (Sleep medicine, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
MELATONIN	Small molecule	Approved	Strong	100	8 trials 26 Cochrane 28 Meta-analysis 137 Trial pubs 107 RCT View evidence Registry trials NCT04233502 — Efficacy and Safety of Slenyto for Insomnia in Children With ASD (WITHDRAWN) PHASE3 NCT02321449 — The Effectiveness of Circadin in Improving Quality of Sleep in Patients Aged 55 or Over (COMPLETED) NCT02156271 — Mechanisms of Sleep Latency and Health: The Effect of a Melatonin Receptor Agonist in Inflammation and Insulin Resistance (COMPLETED) PHASE4 NCT07651605 — Pistacho and Sleep Quality (COMPLETED) NA NCT07542756 — A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia (RECRUITING) PHASE4 NCT07046429 — Affect of Melatonin on Sleep and Cognition in Cirrhosis (RECRUITING) NA NCT04642313 — Comparison of Mg Vs. K Supplementation on Insomnia in Diabetics (UNKNOWN) NA NCT03567395 — Honey to Improve Sleep Quality: a Feasibility Study (COMPLETED) NA Published literature Cochrane review Pharmacological interventions for sleep disturbance ("insomnia") in patients with advanced cancer receiving specialist palliative care: a scoping review (Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2025) Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review From nocturnal awakenings to nocturnal voiding: the relationship between insomnia and nocturia - a systematic review (Minerva urology and nephrology, 2025) Cochrane review Sleep disturbances and the risk of lung cancer: a meta-epidemiological study (BMC cancer, 2023) Cochrane review The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials (Drugs, 2023) Meta-analysis Insomnia among hospitalized inpatients: A systematic review and network meta-analysis (Sleep medicine reviews, 2026) Meta-analysis Factors influencing the effect of melatonin on sleep quality in children with autism spectrum disorder: a systematic review and meta-analysis (Sleep & breathing = Schlaf & Atmung, 2025) 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 trials (Psychiatry and clinical neurosciences, 2025) Meta-analysis Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis (Journal of pineal research, 2024) Systematic review Interventions for Migraine and Sleep: A Systematic Review Exploring Their Bidirectional Association (European journal of neurology, 2026) Systematic review Z-drug abuse and dependence: clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (Arquivos de neuro-psiquiatria, 2025) Systematic review Sleep disorders in patients with spinal cord injury: A comprehensive review of assessment strategies and available treatment (Neurologia i neurochirurgia polska, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
MIRTAZAPINE	Small molecule	Approved	Strong	100	8 trials 3 Cochrane 5 Meta-analysis 14 Trial pubs 11 RCT View evidence Registry trials NCT00561821 — Efficacy and Safety Study of Org 50081 (Esmirtazapine) in Elderly Participants (P05709) (COMPLETED) PHASE3 NCT05247697 — Mirtazapine for Chronic Insomnia in Older Adults (COMPLETED) PHASE1 NCT06443242 — Efficacy and Safety of Low-dose Laser Acupuncture on Treating Insomnia Associated With Major Depressive Disorder (NOT_YET_RECRUITING) NA NCT05978219 — Efficacy of Mirtazapine in Major Depressive Disorder With Insomnia (COMPLETED) PHASE4 NCT00631657 — A 6-Month Efficacy and Safety Study of Org 50081 in Adult Patients With Chronic Primary Insomnia (21106/P05701/MK-8265-002) (COMPLETED) PHASE3 NCT00561574 — A Long-Term Safety Study of Org 50081 (Esmirtazapine) in Elderly Outpatients With Chronic Primary Insomnia (176005/P05697/MK-8265-001) (COMPLETED) PHASE3 NCT00482612 — Study of the Safety and Effectiveness of Esmirtazapine in Participants With Chronic Primary Insomnia (P05706) (COMPLETED) PHASE3 NCT00488072 — Effects of Mirtazapine on Appetite in Advanced Cancer Patients (ACTIVE_NOT_RECRUITING) PHASE2 Published literature Cochrane review Management of insomnia symptoms in depressed patients treated with agomelatine, mirtazapine and trazodone: A systematic review and meta-analysis (Journal of affective disorders, 2026) Cochrane review Efficacy and safety of eszopiclone combined with drug therapy in the treatment of insomnia after stroke: A network meta-analysis and systematic review (PloS one, 2024) Cochrane review Comparative effectiveness of second-generation antidepressants for accompanying anxiety, insomnia, and pain in depressed patients: a systematic review (Depression and anxiety, 2012) Meta-analysis Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis (Sleep medicine, 2024) 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 hypnotics (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2024) Meta-analysis Insomnia and somnolence associated with second-generation antidepressants during the treatment of major depression: a meta-analysis (Journal of clinical psychopharmacology, 2015) Systematic review Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders (Maturitas, 2019) Clinical trial publication Mirtazapine for chronic insomnia in older adults: a randomised double-blind placebo-controlled trial-the MIRAGE study (Age and ageing, 2025) 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) (The British journal of general practice : the journal of the Royal College of General Practitioners, 2025) Clinical trial publication A Pilot Crossover Trial of Sleep Medications for Sleep-disturbed Methadone Maintenance Patients (Journal of addiction medicine, 2020) Clinical trial publication Low doses of mirtazapine or quetiapine for transient insomnia: A randomised, double-blind, cross-over, placebo-controlled trial (Journal of psychopharmacology (Oxford, England), 2017) Clinical trial publication A Phase 2 Randomized Dose-Finding Study With Esmirtazapine in Patients With Primary Insomnia (Journal of clinical psychopharmacology, 2016) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
PENTOBARBITAL	Small molecule	Approved	Strong	100	1 trials 9 Trial pubs 2 RCT View evidence Registry trials NCT01431326 — Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care (COMPLETED) Published literature Clinical trial publication [Periodic discharges of sleep spindles with placebo and zopiclone] (EEG-EMG Zeitschrift fur Elektroenzephalographie, Elektromyographie und verwandte Gebiete, 1992) Clinical trial publication Efficacy and side effects of flunitrazepam and pentobarbital in severely insomniac patients (Journal of clinical pharmacology, 1982) Clinical trial publication [Lormetazepam in preoperative sleeplessness. Dose dependance of the effect and comparison with 100 mg pentobarbital (author's transl)] (Der Anaesthesist, 1979) Clinical trial publication A subjective and objective method assessing the efficacy of hypnotic medications in insomniacs (Journal of clinical pharmacology, 1977) Clinical trial publication Effectiveness of intermediate-term use of secobarbital (Clinical pharmacology and therapeutics, 1976) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
PRAZOSIN	Small molecule	Approved	Strong	100	1 trials 2 Meta-analysis 3 Trial pubs 3 RCT View evidence Registry trials NCT00393874 — Efficacy of Sleep Interventions for Posttraumatic Stress Disorder (PTSD) (COMPLETED) NA Published literature Meta-analysis Factors impacting prazosin efficacy for nightmares and insomnia in PTSD patients - a systematic review and meta-regression analysis (Progress in neuro-psychopharmacology & biological psychiatry, 2025) Meta-analysis Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis (Sleep medicine, 2024) Clinical trial publication A Pilot, Randomized Clinical Trial of Bedtime Doses of Prazosin Versus Placebo in Suicidal Posttraumatic Stress Disorder Patients With Nightmares (Journal of clinical psychopharmacology, 2018) Clinical trial publication Prazosin for Veterans with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence: A Clinical Trial (Alcoholism, clinical and experimental research, 2016) Clinical trial publication Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study (Biological psychiatry, 2008) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
QUAZEPAM	Small molecule	Approved	Strong	100	2 Cochrane 1 Meta-analysis 23 Trial pubs 15 RCT View evidence Published literature Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Insomnia in the elderly (BMJ clinical evidence, 2007) Clinical trial publication Effects of quazepam as a preoperative night hypnotic: comparison with brotizolam (Journal of anesthesia, 2007) Clinical trial publication Hypnotic effects of low doses of quazepam in older insomniacs (Journal of clinical psychopharmacology, 1997) Clinical trial publication Evaluation of the safety and efficacy of quazepam for the treatment of insomnia in psychiatric outpatients (The Journal of clinical psychiatry, 1994) Clinical trial publication Insomnia in generalized anxiety disorder: polysomnographic, psychometric and clinical investigations before, during and after therapy with a long- versus a short-half-life benzodiazepine (quazepam versus triazolam) (Neuropsychobiology, 1994) Clinical trial publication Feasibility of an every-other-night regimen in insomniac patients: subjective hypnotic effectiveness of quazepam, triazolam, and placebo (The Journal of clinical psychiatry, 1993) Randomized controlled trial Objective measurements of daytime sleepiness and performance comparing quazepam with flurazepam in two adult populations using the Multiple Sleep Latency Test (The Journal of clinical psychiatry, 1991) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
RAMELTEON	Small molecule	Approved	Strong	100	8 trials 5 Cochrane 8 Meta-analysis 29 Trial pubs 24 RCT View evidence Registry trials NCT02156271 — Mechanisms of Sleep Latency and Health: The Effect of a Melatonin Receptor Agonist in Inflammation and Insulin Resistance (COMPLETED) PHASE4 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 - (COMPLETED) NCT02058992 — Ramelteon Tablets 8mg Drug Use Surveillance: Survey on Insomnia Associated With Sleep-onset Difficulty (COMPLETED) NCT00755495 — Safety and Efficacy of Ramelteon and Doxepin in Subjects With Chronic Insomnia (COMPLETED) PHASE2 NCT00671294 — Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia. (COMPLETED) PHASE3 NCT00671255 — Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia (COMPLETED) PHASE3 NCT02669082 — The Exploratory Study to Investigate the Effect of Ramelteon for Insomnia Patients With Major Depressive Disorder by Using Actigraphy (COMPLETED) PHASE4 NCT00414102 — Subjective Efficacy of Ramelteon on Sleep in Adults With Chronic Insomnia. (COMPLETED) PHASE4 Published literature 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-analysis (Lancet (London, England), 2022) Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Efficacy and safety of non-benzodiazepine and non-Z-drug hypnotic medication for insomnia in older people: a systematic literature review (European journal of clinical pharmacology, 2020) Cochrane review The efficacy of melatonin and melatonin agonists in insomnia - An umbrella review (Journal of psychiatric research, 2020) Cochrane review Ramelteon in the treatment of chronic insomnia: systematic review and meta-analysis (International journal of clinical practice, 2012) 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 trials (Psychiatry and clinical neurosciences, 2025) 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 hypnotics (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2024) Meta-analysis Efficacy of melatonin and ramelteon for the acute and long-term management of insomnia disorder in adults: A systematic review and meta-analysis (Journal of sleep research, 2023) Meta-analysis Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis (Journal of managed care & specialty pharmacy, 2021) Systematic review Z-drug abuse and dependence: clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (Arquivos de neuro-psiquiatria, 2025) Clinical trial publication Efficacy and Safety of Transitioning to Lemborexant from Z-drug, Suvorexant, and Ramelteon in Japanese Insomnia Patients: An Open-label, Multicenter Study (Advances in therapy, 2024) 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 Harmed (The Journal of clinical psychiatry, 2021) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
SUVOREXANT	Small molecule	Approved	Strong	100	8 trials 11 Cochrane 15 Meta-analysis 29 Trial pubs 24 RCT View evidence Registry trials NCT05823844 — Efficacy of Suvorexant on Post-operative Sleep Disturbance (RECRUITING) PHASE4 NCT03818581 — Suvorexant on Sleep Disturbance in Patients With Chronic Insomnia and Suboptimally Controlled Type 2 Diabetes (COMPLETED) PHASE4 NCT00792298 — Phase IIB 2-Period Crossover Polysomnography Study in Participants With Primary Insomnia (MK-4305-006) (COMPLETED) PHASE2 NCT02684136 — Suvorexant in Insomnia Co-morbid With Fibromyalgia (TERMINATED) PHASE4 NCT06679062 — Suvorexant for Treatment of AUD and PTSD (RECRUITING) PHASE2 NCT03312517 — Study to Compare the Awakening Threshold Effects of Belsomra 10 mg and 20 mg to Placebo in Non-elderly Insomniacs (COMPLETED) PHASE4 NCT01043926 — Pharmacokinetics of Suvorexant in Participants With Hepatic Insufficiency (MK-4305-017) (COMPLETED) PHASE1 NCT01097629 — Safety and Efficacy Study of Suvorexant in Participants With Primary Insomnia - Study B (MK-4305-029) (COMPLETED) PHASE3 Published literature Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review Orexin receptor antagonists in the treatment of insomnia associated with psychiatric disorders: a systematic review (Translational psychiatry, 2024) Cochrane review Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis (Arquivos de neuro-psiquiatria, 2023) Cochrane review The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials (Drugs, 2023) 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-analysis (Lancet (London, England), 2022) Meta-analysis Comparative efficacy and safety of daridorexant, lemborexant, and suvorexant for insomnia: a systematic review and network meta-analysis (Translational psychiatry, 2025) Meta-analysis Association between the use of orexin receptor antagonists and falls or fractures: A meta-analysis (Journal of psychiatric research, 2024) 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 hypnotics (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2024) Meta-analysis Clinical safety and narcolepsy-like symptoms of dual orexin receptor antagonists in patients with insomnia: a systematic review and meta-analysis (Sleep, 2024) Systematic review Efficacy and safety profiles of FDA-approved dual orexin receptor antagonists in depression: A systematic review of pre-clinical and clinical studies (Journal of psychiatric research, 2025) Systematic review The putative effects of orexin receptor antagonists on pain and sleep in humans: A systematic review (Sleep medicine, 2025) Clinical trial publication Smartphone-Based Real-Time Assessment of Daytime Insomnia Symptoms With Suvorexant: A Randomized Clinical Trial (JAMA network open, 2026) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
TEMAZEPAM	Small molecule	Approved	Strong	100	6 trials 4 Cochrane 5 Meta-analysis 61 Trial pubs 38 RCT View evidence Registry trials NCT01519544 — Comparison of Temazepam and Acetazolamide to Treat Difficulty Sleeping at High Altitude (COMPLETED) NA NCT03928301 — Efficacy of Wholetones® 2Sleep Music on Health and Sleep Behaviors of Healthy Adults With Insomnia Symptoms (COMPLETED) NA NCT00245661 — Effects of Temazepam in Patients With Chronic Pulmonary Obstructive Disease (COMPLETED) PHASE3 NCT00940550 — Study to Investigate the Effects of Melatonin, Temazepam & Zolpidem on Sleep EEG in Men and Women (COMPLETED) PHASE1 NCT00465972 — The Treatment of Insomnia in Patients With HIV Disease (COMPLETED) PHASE4 NCT02153788 — Efficacy and Safety of Temazepam in HIV Seropositive Patients With Insomnia (COMPLETED) PHASE4 Published literature Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews (Systematic reviews, 2019) Cochrane review Insomnia in the elderly (BMJ clinical evidence, 2007) Cochrane review Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis (Human psychopharmacology, 2004) Meta-analysis Comparative efficacy and safety of hypnotics for insomnia in older adults: a systematic review and network meta-analysis (Sleep, 2021) Meta-analysis Pharmacological agents for improving sleep quality at high altitude: a systematic review and meta-analysis of randomized controlled trials (Sleep medicine, 2018) Meta-analysis Toward evidence-based prescribing at end of life: a comparative review of temazepam and zolpidem for the treatment of insomnia (The American journal of hospice & palliative care, 2003) Clinical trial publication Masked Taper With Behavioral Intervention for Discontinuation of Benzodiazepine Receptor Agonists: A Randomized Clinical Trial (JAMA internal medicine, 2024) Clinical trial publication Temazepam or Melatonin Versus Placebo for the Treatment of Insomnia in Advanced Cancer: A Three-Arm, Double-Blind, Phase III, Multicenter, Randomized Clinical Trial (Journal of palliative medicine, 2024) Clinical trial publication Withdrawal from long-term use of zopiclone, zolpidem and temazepam may improve perceived sleep and quality of life in older adults with primary insomnia (Basic & clinical pharmacology & toxicology, 2019) Clinical trial publication Long-term persistence of withdrawal of temazepam, zopiclone, and zolpidem in older adults: a 3-year follow-up study (BMC geriatrics, 2018) Clinical trial publication Handgrip strength and balance in older adults following withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotics (BMC geriatrics, 2014) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
TRIAZOLAM	Small molecule	Approved	Strong	100	1 trials 3 Cochrane 5 Meta-analysis 93 Trial pubs 55 RCT View evidence Registry trials NCT01888497 — Next-Day Residual Effects of Gabapentin, Diphenhydramine and Triazolam on Simulated Driving Performance in Normal Volunteers (COMPLETED) PHASE3 Published literature Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews (Systematic reviews, 2019) Cochrane review Insomnia in the elderly (BMJ clinical evidence, 2007) 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 trials (Psychiatry and clinical neurosciences, 2025) 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 hypnotics (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2024) Meta-analysis Comparative efficacy and safety of hypnotics for insomnia in older adults: a systematic review and network meta-analysis (Sleep, 2021) Meta-analysis Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies (International clinical psychopharmacology, 1999) Systematic review Pharmacological treatment of insomnia in alcohol recovery: a systematic review (Alcohol and alcoholism (Oxford, Oxfordshire), 2011) Clinical trial publication Effects of different doses of triazolam in the middle-of-the-night insomnia: a double-blind, randomized, parallel group study (Journal of neurology, 2017) Clinical trial publication CAP variables and arousals as sleep electroencephalogram markers for primary insomnia (Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2003) Clinical trial publication Nighttime versus daytime hypnotic self-administration (Psychopharmacology, 2002) Clinical trial publication A double-blind, randomized and placebo-controlled study on the polysomnographic withdrawal effects of zopiclone, zolpidem and triazolam in healthy subjects (European archives of psychiatry and clinical neuroscience, 2001) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ZALEPLON	Small molecule	Approved	Strong	100	7 trials 10 Cochrane 14 Meta-analysis 14 Trial pubs 13 RCT View evidence Registry trials NCT00878553 — Study of Sleep-maintenance Activity of 3 Doses of SKP-1041 (COMPLETED) PHASE2 NCT01277107 — A Polysomnographic Study to Compare the Efficacy of Gastric Retentive Zaleplon Accordion Pill to Placebo in Subjects With Insomnia (COMPLETED) PHASE2 NCT03928301 — Efficacy of Wholetones® 2Sleep Music on Health and Sleep Behaviors of Healthy Adults With Insomnia Symptoms (COMPLETED) NA NCT00694187 — Bioequivalency Study of Zaleplon 10 mg Capsules Under Fasting Conditions (COMPLETED) NA NCT00694317 — Bioequivalency Study of Zaleplon 10 mg Capsules Under Fed Conditions (COMPLETED) NA NCT06640023 — The Study in Outpatient Medicine Using Nudges to Improve Sleep (ACTIVE_NOT_RECRUITING) NA NCT03489304 — Zaleplon in HIV Patients With Depression (COMPLETED) PHASE2 Published literature Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review Comparative efficacy of hypnotics in young and middle-aged adults with insomnia: a systematic review and network meta-analysis (Sleep & breathing = Schlaf & Atmung, 2023) 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-analysis (Lancet (London, England), 2022) Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Drug treatment of primary insomnia: a meta-analysis of polysomnographic randomized controlled trials (CNS drugs, 2014) Meta-analysis Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis (Sleep medicine reviews, 2023) Meta-analysis Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis (Journal of managed care & specialty pharmacy, 2021) Systematic review Clinical practice guidelines for switching or deprescribing hypnotic medications for chronic insomnia: Results of European neuropsychopharmacology and sleep expert's consensus group (Sleep medicine, 2025) 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 Harmed (The Journal of clinical psychiatry, 2021) Clinical trial publication Enhancement of zaleplon oral bioavailability using optimized self-nano emulsifying drug delivery systems and its effect on sleep quality among a sample of psychiatric patients (Drug delivery, 2019) Clinical trial publication Patient Education and Pharmacist Consultation Influence on Nonbenzodiazepine Sedative Medication Deprescribing Success for Older Adults (The Permanente journal, 2019) Clinical trial publication A double-blind, randomized, comparative study to evaluate the efficacy and safety of zaleplon versus zolpidem in shortening sleep latency in primary insomnia (Chang Gung medical journal, 2011) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ZOLPIDEM TARTRATE	Small molecule	Approved	Strong	100	8 trials 2 Meta-analysis 13 Trial pubs 13 RCT View evidence Registry trials NCT05456152 — Safety and Efficacy of Zolpidem in the Long-Term Treatment of Insomnia (UNKNOWN) PHASE3 NCT00156533 — Long Term Treatment With Zolpidem: Nightly and Intermittent Dosing (COMPLETED) PHASE4 NCT00662155 — The Role of Partial Reinforcement in the Long Term Management of Insomnia (COMPLETED) NA NCT01685073 — The Role of Sleep in the Treatment of Cannabis Use Disorders (COMPLETED) PHASE2, PHASE3 NCT07542756 — A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia (RECRUITING) PHASE4 NCT00044629 — Combined Behavioral/Pharmacological Therapy for Insomnia (COMPLETED) PHASE2 NCT02839200 — Efficacy and Safety of ACT-541468 in Adult Subjects With Insomnia Disorder (COMPLETED) PHASE2 NCT00530556 — Insomnia and Daytime Function in Osteoarthritis (COMPLETED) PHASE4 Published literature Meta-analysis Lemborexant vs suvorexant for insomnia: A systematic review and network meta-analysis (Journal of psychiatric research, 2020) Meta-analysis Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy (JAMA, 1997) Clinical trial publication Effect of lemborexant on sleep architecture in participants with insomnia disorder and mild obstructive sleep apnea (Sleep medicine, 2025) Clinical trial publication Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials (Drugs & aging, 2024) Clinical trial publication Comparison of the treatment effectiveness between lemborexant and zolpidem tartrate extended-release for insomnia disorder subtypes defined based on polysomnographic findings (Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2023) Clinical trial publication Comparison of the effect of lemborexant with placebo and zolpidem tartrate extended release on sleep architecture in older adults with insomnia disorder (Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2021) Clinical trial publication Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening (Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2020) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ACEBUTOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETAZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ADUCANUMAB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
APIXABAN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
APOMORPHINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ASENAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATIPAMEZOLE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BENZPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BEPRIDIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BEPRIDIL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BETAXOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BETHANIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BICALUTAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BISOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE TARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BROMOCRIPTINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BUPROPION HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CABERGOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CARBACHOL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CARVEDILOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CELECOXIB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CELIPROLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CHEMBL407	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
CHLORPROMAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CHOLESTEROL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CHORIOGONADOTROPIN ALFA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CIPROFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLOMIPRAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLONIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	3 trials View evidence Registry trials NCT04278404 — Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) (RECRUITING) NCT05618002 — Lemborexant vs Zopiclone vs Clonidine for Insomnia Treatment in Chronic Pain Patients (RECRUITING) NCT05277038 — Clonidine is Better Than Zopiclone for Insomnia Treatment in Chronic Pain Patients (COMPLETED) CT.gov search · Cochrane · PubMed	DGIdb	—
CYCLOBENZAPRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEBRISOQUIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXMEDETOMIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXTROAMPHETAMINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DICHLORPHENAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIETHYLSTILBESTROL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIPIVEFRIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIPIVEFRIN HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DONANEMAB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DONEPEZIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DOPAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DOXAZOSIN MESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DROXIDOPA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
EPHEDRINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPHEDRINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPINEPHRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
EPINEPHRINE BITARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPIRUBICIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ERGOLOID MESYLATES Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ERGOLOID MESYLATES, USP Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ERGOTAMINE TARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ESMOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ETHOXZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ETOMIDATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOFIBRATE MICRONIZED Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOLDOPAM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUTICASONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUVASTATIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GABAPENTIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GABAPENTIN ENACARBIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GALANTAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GANCICLOVIR Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ ACETATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
HYDROXYAMPHETAMINE HYDROBROMIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ILOPERIDONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
IMIPRAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDAPAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDOMETHACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
IRBESARTAN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ISOPROTERENOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ISOSORBIDE DINITRATE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
LABETALOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LABETALOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LECANEMAB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LEVONORDEFRIN Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
LITHIUM CATION Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LORAZEPAM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LURASIDONE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
LUTEIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MAFENIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MECAMYLAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MEPERIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MEPHENTERMINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METHAMPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METHAZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHOXSALEN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHYLDOPA ANHYDROUS Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METHYLDOPATE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
METOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MIANSERIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MILNACIPRAN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MIRTAZAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MONTELUKAST SODIUM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXISYLYTE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXONIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NADOLOL Repurposing	Small molecule	Approved	Strong	95	1 pubs View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
NALIDIXIC ACID Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NAPHAZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NAPHAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NEBIVOLOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NICOTINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NICOTINE POLACRILEX Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NISOLDIPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE BITARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NORETHINDRONE ACETATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
NORFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NORTRIPTYLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
OFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
OLANZAPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PERGOLIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENTOLAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENTOLAMINE MESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLPROPANOLAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENYTOIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PINDOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAVASTATIN SODIUM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PREDNISONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PREGABALIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PROPRANOLOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
PROPYLHEXEDRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
PSEUDOEPHEDRINE POLISTIREX Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RACEPINEPHRINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RAUWOLFIA SERPENTINA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
RAUWOLFIA SERPENTINA (USP) Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
REMIFENTANIL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RILMENIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RISPERIDONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RITONAVIR Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
RIVASTIGMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SIROLIMUS Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
SODIUM CHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SOTALOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
SULBACTAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
SULOCTIDIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TACROLIMUS ANHYDROUS Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TAZOBACTAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TERODILINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TETRAHYDROZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TETRAHYDROZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TIZANIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TIZANIDINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TOLAZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TOLAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TRAZODONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TRETINOIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TRIAMCINOLONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TROGLITAZONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
TROGLITAZONE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
XYLAZINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
YOHIMBINE Repurposing	Small molecule	Approved	Strong	95	1 Meta-analysis View evidence Published literature Meta-analysis Herbal medications for common ailments in the elderly (Drugs & aging, 1999) CT.gov search · Cochrane · PubMed	DGIdb	—
ALMOREXANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
AMITRIPTYLINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
BROTIZOLAM	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CANNABIDIOL	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXMEDETOMIDINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
EPLIVANSERIN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
ESMIRTAZAPINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
FAZAMOREXANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
GABAPENTIN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
ORN-0829 HYDRATE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
QUETIAPINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
SELTOREXANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
SERTRALINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
TRAZODONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CHEMBL1059	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1200750	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL2107339	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
DARIDOREXANT	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
ESTROGEN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
GABOXADOL	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
INDIPLON	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
LORMETAZEPAM	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LUMATEPERONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
NALTREXONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
TASIMELTEON	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
TRAZODONE HYDROCHLORIDE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
VENLAFAXINE HYDROCHLORIDE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
VOLINANSERIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ZOLPIDEM	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
ZOPICLONE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
ZURANOLONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
DARAPLADIB Repurposing	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
FENRETINIDE Repurposing	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
ADIPIPLON	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ARMODAFINIL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ATAGABALIN	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CANNABINOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
FILOREXANT	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LY2624803	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
MODAFINIL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NELOTANSERIN	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
PIROMELATINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
SB-649868	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
SUNOBINOP	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
(-)-LIMONENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
(-)-LINALOOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ALPHA-PINENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ALPHA-TERPINENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ALPHA-TERPINEOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BENZODIAZEPINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BETA-CARYOPHYLLENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CHEMBL1201178	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1672054	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL3338865	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CITALOPRAM	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DIMDAZENIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DOXEPIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DRONABINOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ESCITALOPRAM OXALATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FERROUS SULFATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FLUOXETINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ILOPERIDONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LINALOOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LINALOOL (+)	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MYRCENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
OXALOACETATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
PALIPERIDONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
PHYTOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
PIMAVANSERIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SODIUM OXYBATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SOLRIAMFETOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TASIPIMIDINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TESAMORELIN	Biologic	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CHEMBL:CHEMBL401844 Repurposing	Small molecule	Phase II	Emerging	50	—	DGIdb	ChEMBL Open Targets
FD1 Repurposing	Small molecule	Phase II	Emerging	50	—	DGIdb	—
SKF-83566 Repurposing	Small molecule	Phase II	Emerging	50	—	DGIdb	—
ALPRENOLOL Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
AMIFLOXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
BROLAMFETAMINE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
CARZENIDE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIFLOXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIMECAMINE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ELLAGIC ACID Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ENISOPROST Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FENCAMFAMIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FLEROXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
IDOXIFENE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
LYSERGIDE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
MERAFLOXACIN Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
TENAMFETAMINE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ZIDAPAMIDE Repurposing	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FLURAZEPAM	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
PROPOFOL	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
SUNOBINOP TOSYLATE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
CHEMBL2106049	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
PIPAMPERONE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
AMOBARBITAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
APROBARBITAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BARBITAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUTABARBITAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUTETHAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CARPHENAZINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CHEMBL25	Small molecule	Preclinical	Emerging	15	—	ChEMBL	ChEMBL Open Targets
CIPEPOFOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CLONAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CLONIDINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DYDROGESTERONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ELEUTHERO	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ESCITALOPRAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ESTRADIOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ETHCHLORVYNOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ETHINAMATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUNITRAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUVOXAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GLUTETHIMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LIDOCAINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LORAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MAGNESIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
METHAQUALONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
METHYPRYLON	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MIDAZOLAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NABILONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NITRAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
OBETICHOLIC ACID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PARALDEHYDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PROGESTERONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PROPIOMAZINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRICLOFOS SODIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VALERIAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
DARIDOREXANT HYDROCHLORIDE	Small molecule	Approved	Strong	100	1 trials View evidence Registry trials NCT02571855 — A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of ACT-541468 in Healthy Young Adults and Elderly Subjects (COMPLETED) PHASE1 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
DIPHENHYDRAMINE HYDROCHLORIDE	Small molecule	Approved	Strong	100	8 trials 1 Trial pubs View evidence Registry trials NCT07542756 — A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia (RECRUITING) PHASE4 NCT04396327 — SM-1 vs. an Active Comparator in A Model of Transient Insomnia (NOT_YET_RECRUITING) PHASE2 NCT03338764 — An Investigational Study to Assess Efficacy and Pattern of Use of SM-1 in Subjects With a History of Transient Insomnia (WITHDRAWN) PHASE3 NCT02671760 — Pilot Study of a Combination Drug Product for Treatment of Short-term Insomnia (COMPLETED) PHASE2 NCT03968939 — Total Joint Arthroplasty and Sleep (COMPLETED) PHASE4 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 (UNKNOWN) PHASE3 NCT03331042 — SM-1 vs 2 Comparators and Placebo in Participants With a History of Transient Insomnia. (COMPLETED) PHASE3 NCT02578186 — Evaluation of Diphenhydramine Hydrochloride Effects in Subjects With Occasional Sleeplessness (COMPLETED) PHASE4 Published literature Clinical trial publication Clinical evaluation of diphenhydramine hydrochloride for the treatment of insomnia in psychiatric patients: a double-blind study (Journal of clinical pharmacology, 1990) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
DOXEPIN HYDROCHLORIDE	Small molecule	Approved	Strong	100	5 trials View evidence Registry trials NCT07542756 — A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia (RECRUITING) PHASE4 NCT00755495 — Safety and Efficacy of Ramelteon and Doxepin in Subjects With Chronic Insomnia (COMPLETED) PHASE2 NCT07598734 — Doxepin Alone or Combined With Ramelteon Versus Placebo for Improving Sleep Quality After Primary Total Knee Arthroplasty (NOT_YET_RECRUITING) PHASE4 NCT01489982 — Treatments for Insomnia in Patients With Parkinson's Disease (COMPLETED) EARLY_PHASE1 NCT00465972 — The Treatment of Insomnia in Patients With HIV Disease (COMPLETED) PHASE4 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ESTAZOLAM	Small molecule	Approved	Strong	100	8 trials 3 Cochrane 5 Meta-analysis 43 Trial pubs 39 RCT View evidence Registry trials NCT03997058 — Observation on the Effect of Auricular Acupoint Pressing on Insomnia and Adverse Events in MHD (UNKNOWN) PHASE4 NCT00347295 — Randomised, Double-blind Study to Investigate the Safety and Efficacy of Brotizolam in Insomnia Outpatients. (COMPLETED) PHASE3 NCT00956319 — A Study to Evaluate Efficacy and Safety of Zolpidem Modified Release Formulation in Insomnia Patients (COMPLETED) PHASE4 NCT06859190 — Efficacy of Auricular Pressure Beans with Electroacupuncture and Estazolam Treating Insomnia Caused by Cancer (RECRUITING) PHASE3 NCT05452577 — Treatment of Chronic Insomnia According to Yin Yang Theory and Its Correlation With Circadian Rhythm (COMPLETED) NA NCT07306494 — Compound Ciwujia Granules in the Treatment of Insomnia (NOT_YET_RECRUITING) PHASE4 NCT06212934 — "Chou's Tiaoshen" Acupoints for Short-term Insomnia. (UNKNOWN) NA NCT06258226 — A Randomized Controlled Trial of Auricular Acupressure in Treating Estazolam-dependent Insomnia (UNKNOWN) NA Published literature Cochrane review Efficacy and safety of Chaihu plus Longgu Muli decoction combined with Estazolam in the treatment of insomnia: a meta-analysis (Sleep & breathing = Schlaf & Atmung, 2025) Cochrane review Acupuncture for cancer-related insomnia: A systematic review and meta-analysis (Phytomedicine : international journal of phytotherapy and phytopharmacology, 2022) Cochrane review Clinical effectiveness of Tui Na for insomnia compared with estazolam: A systematic review and meta-analysis of randomized controlled trials (Complementary therapies in medicine, 2019) Meta-analysis Acupuncture for Primary Insomnia: An Updated Systematic Review of Randomized Controlled Trials (Journal of alternative and complementary medicine (New York, N.Y.), 2019) Meta-analysis Auricular acupuncture for insomnia: a systematic review (International journal of clinical practice, 2008) Clinical trial publication [Clinical efficacy of acupuncture combined with estazolam on chronic insomnia] (Zhen ci yan jiu = Acupuncture research, 2026) Clinical trial publication Suanzaoren decoction improving chronic insomnia with little effects on functional connectivity within the sensorimotor network (Brain research, 2026) Clinical trial publication Altered cerebral functional activity and its associated genetic profiles underlying chronic insomnia disorder before and after treatment (The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2025) Clinical trial publication [Effects of Tiaoshu Anshen acupuncture on sleep quality and serum neurotransmitter levels in patients with chronic insomnia] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2025) Clinical trial publication [Clinical effect of the warm acupuncture of Mongolian medicine on insomnia in the elderly and its brain-gut peptide mechanism: a randomized controlled trial] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2024) Randomized controlled trial [Clinical effect of acupuncture based on syndrome differentiation in the treatment of chronic insomnia and its influence on cognitive function] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2023) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ESZOPICLONE	Small molecule	Approved	Strong	100	8 trials 10 Cochrane 18 Meta-analysis 43 Trial pubs 41 RCT View evidence Registry trials NCT06452953 — Modified Suanzaoren Decoction Versus Eszopiclone for the Treatment of Chronic Insomnia Disorder (COMPLETED) NA NCT00367965 — Study of Eszopiclone Compared to Placebo on Daytime Function in Subjects With Insomnia Related to Rheumatoid Arthritis (COMPLETED) PHASE3 NCT00247624 — Improving Sleep and Psychological Functioning in People With Depression and Insomnia (COMPLETED) PHASE4 NCT01710631 — Twelve Month Study of the Safety of Eszopiclone in Adult Subjects With Insomnia (COMPLETED) PHASE3 NCT01605253 — Eszopiclone for the Treatment of Posttraumatic Stress Disorder (COMPLETED) PHASE4 NCT07018557 — Impact of Eszopiclone on Blood Pressure in Patients With Insomnia and Hypertension (PRYSMA-HTN) (RECRUITING) PHASE4 NCT04980703 — Grain Moxibustion Treatment on Insomnia: a Randomized Controlled Trial (NOT_YET_RECRUITING) NA NCT00856973 — Safety & Efficacy Study of Study Drug (Eszopiclone) in Children and Adolescents With Attention-deficit/Hyperactivity Disorder - Associated Insomnia (COMPLETED) PHASE3 Published literature Cochrane review Comparative efficacy of positive airway pressure-based combination therapy in comorbid insomnia and sleep apnea: A systematic review and network meta-analysis (Sleep medicine reviews, 2026) Cochrane review Efficacy of auriculotherapies for primary insomnia: A systematic review and network meta-analysis (Medicine, 2026) Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review Comparative efficacy and safety of different pharmacological interventions for the treatment of depression associated with insomnia in the elderly population: a systematic review and network meta-analysis (Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society, 2025) Cochrane review Efficacy and safety of eszopiclone combined with drug therapy in the treatment of insomnia after stroke: A network meta-analysis and systematic review (PloS one, 2024) Meta-analysis Efficacy and Acceptability of Licensed and Off-Label Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness: A Systematic Review and Meta-Analysis of Randomised Trials (Acta psychiatrica Scandinavica, 2025) Systematic review Evidence-based pharmacological interventions for insomnia: a systematic review on the effects of eszopiclone on insomnia comorbid with mental disturbances (The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2026) Systematic review Z-drug abuse and dependence: clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (Arquivos de neuro-psiquiatria, 2025) Clinical trial publication [Tiaowei Jiannao acupuncture for post-ischemic stroke insomnia: a randomized controlled trial] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2025) Clinical trial publication A Mechanistic study assessing difficulty discontinuing chronic hypnotic use (Psychopharmacology, 2025) Clinical trial publication Cognitive Behavioral Therapy Alone or in Combination with Eszopiclone in Comorbid Insomnia and Obstructive Sleep Apnea in Veterans with Posttraumatic Stress Disorder: A Randomized Trial (The Psychiatric quarterly, 2025) Clinical trial publication Efficacy and Safety of Transitioning to Lemborexant from Z-drug, Suvorexant, and Ramelteon in Japanese Insomnia Patients: An Open-label, Multicenter Study (Advances in therapy, 2024) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
FLURAZEPAM HYDROCHLORIDE	Small molecule	Approved	Strong	100	6 Trial pubs 2 RCT View evidence Published literature Clinical trial publication Double-blind evaluation of temazepam, flurazepam, and placebo in geriatric insomniacs (Clinical therapeutics, 1982) Clinical trial publication Insomnia in the elderly: treatment with flurazepam hydrochloride (Journal of the American Geriatrics Society, 1979) Clinical trial publication Comparison of the hypnotic activity of triazolam, flurazepam hydrochloride, and placebo (Clinical pharmacology and therapeutics, 1975) Clinical trial publication A double-blind evaluation of a new hypnotic--flurazepam hydrochloride (South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 1973) Clinical trial publication Controlled evaluation of flurazepam hydrochloride, a new nonbarbiturate hypnotic (Military medicine, 1973) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
LEMBOREXANT	Small molecule	Approved	Strong	100	8 trials 9 Cochrane 16 Meta-analysis 25 Trial pubs 21 RCT View evidence Registry trials NCT06981195 — Effects of Lemborexant on Insomnia and Its Relationship to Mood and Behavior on Opioid Use Disorder Subjects (RECRUITING) PHASE2 NCT02350309 — Study to Evaluate the Effect of 2 Dosage Strengths of Lemborexant (E2006) on a Multiple Sleep Latency Test in Participants With Insomnia Disorder (COMPLETED) PHASE1 NCT04742699 — An Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Transitioning to Lemborexant in Japanese Subjects With Insomnia (COMPLETED) PHASE4 NCT02783729 — Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1) (COMPLETED) PHASE3 NCT05594589 — A Study to Assess the Pharmacodynamics of Lemborexant in Korean Participants With Insomnia Disorder (COMPLETED) PHASE2 NCT01463098 — A 2-Part Single Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006 (COMPLETED) PHASE1 NCT06496282 — Lemborexant on Improving Sleep Quality Among Hospital Rotating Shift Workers (RECRUITING) PHASE3 NCT05618002 — Lemborexant vs Zopiclone vs Clonidine for Insomnia Treatment in Chronic Pain Patients (RECRUITING) Published literature Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review Efficacy and safety of lemborexant in patients with insomnia: a systematic review and meta-analysis (Sleep medicine, 2025) Cochrane review Efficacy and safety of lemborexant vs placebo in treating adults with insomnia disorder: a systematic review and meta-analysis of 1976 patients (Naunyn-Schmiedeberg's archives of pharmacology, 2025) Cochrane review Orexin receptor antagonists in the treatment of insomnia associated with psychiatric disorders: a systematic review (Translational psychiatry, 2024) Cochrane review Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis (Arquivos de neuro-psiquiatria, 2023) Meta-analysis Comparative efficacy and safety of daridorexant, lemborexant, and suvorexant for insomnia: a systematic review and network meta-analysis (Translational psychiatry, 2025) Meta-analysis Comparison of efficacy and safety of dual orexin receptor antagonists lemborexant and daridorexant for the treatment of insomnia: a systematic review and meta-analysis (Psychopharmacology, 2025) Systematic review Efficacy and safety profiles of FDA-approved dual orexin receptor antagonists in depression: A systematic review of pre-clinical and clinical studies (Journal of psychiatric research, 2025) Systematic review The putative effects of orexin receptor antagonists on pain and sleep in humans: A systematic review (Sleep medicine, 2025) Clinical trial publication A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial of lemborexant in adults with insomnia disorder (Sleep medicine, 2026) Clinical trial publication Effect of lemborexant on sleep parameters and architecture in adult and elderly participants with mild-to-severe obstructive sleep apnea (Sleep medicine, 2025) Clinical trial publication Effect of lemborexant on sleep architecture in participants with insomnia disorder and mild obstructive sleep apnea (Sleep medicine, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
MELATONIN	Small molecule	Approved	Strong	100	8 trials 26 Cochrane 28 Meta-analysis 137 Trial pubs 107 RCT View evidence Registry trials NCT04233502 — Efficacy and Safety of Slenyto for Insomnia in Children With ASD (WITHDRAWN) PHASE3 NCT02321449 — The Effectiveness of Circadin in Improving Quality of Sleep in Patients Aged 55 or Over (COMPLETED) NCT02156271 — Mechanisms of Sleep Latency and Health: The Effect of a Melatonin Receptor Agonist in Inflammation and Insulin Resistance (COMPLETED) PHASE4 NCT07651605 — Pistacho and Sleep Quality (COMPLETED) NA NCT07542756 — A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia (RECRUITING) PHASE4 NCT07046429 — Affect of Melatonin on Sleep and Cognition in Cirrhosis (RECRUITING) NA NCT04642313 — Comparison of Mg Vs. K Supplementation on Insomnia in Diabetics (UNKNOWN) NA NCT03567395 — Honey to Improve Sleep Quality: a Feasibility Study (COMPLETED) NA Published literature Cochrane review Pharmacological interventions for sleep disturbance ("insomnia") in patients with advanced cancer receiving specialist palliative care: a scoping review (Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2025) Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review From nocturnal awakenings to nocturnal voiding: the relationship between insomnia and nocturia - a systematic review (Minerva urology and nephrology, 2025) Cochrane review Sleep disturbances and the risk of lung cancer: a meta-epidemiological study (BMC cancer, 2023) Cochrane review The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials (Drugs, 2023) Meta-analysis Insomnia among hospitalized inpatients: A systematic review and network meta-analysis (Sleep medicine reviews, 2026) Meta-analysis Factors influencing the effect of melatonin on sleep quality in children with autism spectrum disorder: a systematic review and meta-analysis (Sleep & breathing = Schlaf & Atmung, 2025) 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 trials (Psychiatry and clinical neurosciences, 2025) Meta-analysis Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis (Journal of pineal research, 2024) Systematic review Interventions for Migraine and Sleep: A Systematic Review Exploring Their Bidirectional Association (European journal of neurology, 2026) Systematic review Z-drug abuse and dependence: clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (Arquivos de neuro-psiquiatria, 2025) Systematic review Sleep disorders in patients with spinal cord injury: A comprehensive review of assessment strategies and available treatment (Neurologia i neurochirurgia polska, 2025) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
MIRTAZAPINE	Small molecule	Approved	Strong	100	8 trials 3 Cochrane 5 Meta-analysis 14 Trial pubs 11 RCT View evidence Registry trials NCT00561821 — Efficacy and Safety Study of Org 50081 (Esmirtazapine) in Elderly Participants (P05709) (COMPLETED) PHASE3 NCT05247697 — Mirtazapine for Chronic Insomnia in Older Adults (COMPLETED) PHASE1 NCT06443242 — Efficacy and Safety of Low-dose Laser Acupuncture on Treating Insomnia Associated With Major Depressive Disorder (NOT_YET_RECRUITING) NA NCT05978219 — Efficacy of Mirtazapine in Major Depressive Disorder With Insomnia (COMPLETED) PHASE4 NCT00631657 — A 6-Month Efficacy and Safety Study of Org 50081 in Adult Patients With Chronic Primary Insomnia (21106/P05701/MK-8265-002) (COMPLETED) PHASE3 NCT00561574 — A Long-Term Safety Study of Org 50081 (Esmirtazapine) in Elderly Outpatients With Chronic Primary Insomnia (176005/P05697/MK-8265-001) (COMPLETED) PHASE3 NCT00482612 — Study of the Safety and Effectiveness of Esmirtazapine in Participants With Chronic Primary Insomnia (P05706) (COMPLETED) PHASE3 NCT00488072 — Effects of Mirtazapine on Appetite in Advanced Cancer Patients (ACTIVE_NOT_RECRUITING) PHASE2 Published literature Cochrane review Management of insomnia symptoms in depressed patients treated with agomelatine, mirtazapine and trazodone: A systematic review and meta-analysis (Journal of affective disorders, 2026) Cochrane review Efficacy and safety of eszopiclone combined with drug therapy in the treatment of insomnia after stroke: A network meta-analysis and systematic review (PloS one, 2024) Cochrane review Comparative effectiveness of second-generation antidepressants for accompanying anxiety, insomnia, and pain in depressed patients: a systematic review (Depression and anxiety, 2012) Meta-analysis Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis (Sleep medicine, 2024) 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 hypnotics (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2024) Meta-analysis Insomnia and somnolence associated with second-generation antidepressants during the treatment of major depression: a meta-analysis (Journal of clinical psychopharmacology, 2015) Systematic review Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders (Maturitas, 2019) Clinical trial publication Mirtazapine for chronic insomnia in older adults: a randomised double-blind placebo-controlled trial-the MIRAGE study (Age and ageing, 2025) 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) (The British journal of general practice : the journal of the Royal College of General Practitioners, 2025) Clinical trial publication A Pilot Crossover Trial of Sleep Medications for Sleep-disturbed Methadone Maintenance Patients (Journal of addiction medicine, 2020) Clinical trial publication Low doses of mirtazapine or quetiapine for transient insomnia: A randomised, double-blind, cross-over, placebo-controlled trial (Journal of psychopharmacology (Oxford, England), 2017) Clinical trial publication A Phase 2 Randomized Dose-Finding Study With Esmirtazapine in Patients With Primary Insomnia (Journal of clinical psychopharmacology, 2016) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
PENTOBARBITAL	Small molecule	Approved	Strong	100	1 trials 9 Trial pubs 2 RCT View evidence Registry trials NCT01431326 — Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care (COMPLETED) Published literature Clinical trial publication [Periodic discharges of sleep spindles with placebo and zopiclone] (EEG-EMG Zeitschrift fur Elektroenzephalographie, Elektromyographie und verwandte Gebiete, 1992) Clinical trial publication Efficacy and side effects of flunitrazepam and pentobarbital in severely insomniac patients (Journal of clinical pharmacology, 1982) Clinical trial publication [Lormetazepam in preoperative sleeplessness. Dose dependance of the effect and comparison with 100 mg pentobarbital (author's transl)] (Der Anaesthesist, 1979) Clinical trial publication A subjective and objective method assessing the efficacy of hypnotic medications in insomniacs (Journal of clinical pharmacology, 1977) Clinical trial publication Effectiveness of intermediate-term use of secobarbital (Clinical pharmacology and therapeutics, 1976) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
QUAZEPAM	Small molecule	Approved	Strong	100	2 Cochrane 1 Meta-analysis 23 Trial pubs 15 RCT View evidence Published literature Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Insomnia in the elderly (BMJ clinical evidence, 2007) Clinical trial publication Effects of quazepam as a preoperative night hypnotic: comparison with brotizolam (Journal of anesthesia, 2007) Clinical trial publication Hypnotic effects of low doses of quazepam in older insomniacs (Journal of clinical psychopharmacology, 1997) Clinical trial publication Evaluation of the safety and efficacy of quazepam for the treatment of insomnia in psychiatric outpatients (The Journal of clinical psychiatry, 1994) Clinical trial publication Insomnia in generalized anxiety disorder: polysomnographic, psychometric and clinical investigations before, during and after therapy with a long- versus a short-half-life benzodiazepine (quazepam versus triazolam) (Neuropsychobiology, 1994) Clinical trial publication Feasibility of an every-other-night regimen in insomniac patients: subjective hypnotic effectiveness of quazepam, triazolam, and placebo (The Journal of clinical psychiatry, 1993) Randomized controlled trial Objective measurements of daytime sleepiness and performance comparing quazepam with flurazepam in two adult populations using the Multiple Sleep Latency Test (The Journal of clinical psychiatry, 1991) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
RAMELTEON	Small molecule	Approved	Strong	100	8 trials 5 Cochrane 8 Meta-analysis 29 Trial pubs 24 RCT View evidence Registry trials NCT02156271 — Mechanisms of Sleep Latency and Health: The Effect of a Melatonin Receptor Agonist in Inflammation and Insulin Resistance (COMPLETED) PHASE4 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 - (COMPLETED) NCT02058992 — Ramelteon Tablets 8mg Drug Use Surveillance: Survey on Insomnia Associated With Sleep-onset Difficulty (COMPLETED) NCT00755495 — Safety and Efficacy of Ramelteon and Doxepin in Subjects With Chronic Insomnia (COMPLETED) PHASE2 NCT00671294 — Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia. (COMPLETED) PHASE3 NCT00671255 — Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia (COMPLETED) PHASE3 NCT02669082 — The Exploratory Study to Investigate the Effect of Ramelteon for Insomnia Patients With Major Depressive Disorder by Using Actigraphy (COMPLETED) PHASE4 NCT00414102 — Subjective Efficacy of Ramelteon on Sleep in Adults With Chronic Insomnia. (COMPLETED) PHASE4 Published literature 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-analysis (Lancet (London, England), 2022) Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Efficacy and safety of non-benzodiazepine and non-Z-drug hypnotic medication for insomnia in older people: a systematic literature review (European journal of clinical pharmacology, 2020) Cochrane review The efficacy of melatonin and melatonin agonists in insomnia - An umbrella review (Journal of psychiatric research, 2020) Cochrane review Ramelteon in the treatment of chronic insomnia: systematic review and meta-analysis (International journal of clinical practice, 2012) 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 trials (Psychiatry and clinical neurosciences, 2025) 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 hypnotics (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2024) Meta-analysis Efficacy of melatonin and ramelteon for the acute and long-term management of insomnia disorder in adults: A systematic review and meta-analysis (Journal of sleep research, 2023) Meta-analysis Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis (Journal of managed care & specialty pharmacy, 2021) Systematic review Z-drug abuse and dependence: clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (Arquivos de neuro-psiquiatria, 2025) Clinical trial publication Efficacy and Safety of Transitioning to Lemborexant from Z-drug, Suvorexant, and Ramelteon in Japanese Insomnia Patients: An Open-label, Multicenter Study (Advances in therapy, 2024) 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 Harmed (The Journal of clinical psychiatry, 2021) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
SUVOREXANT	Small molecule	Approved	Strong	100	8 trials 11 Cochrane 15 Meta-analysis 29 Trial pubs 24 RCT View evidence Registry trials NCT05823844 — Efficacy of Suvorexant on Post-operative Sleep Disturbance (RECRUITING) PHASE4 NCT03818581 — Suvorexant on Sleep Disturbance in Patients With Chronic Insomnia and Suboptimally Controlled Type 2 Diabetes (COMPLETED) PHASE4 NCT00792298 — Phase IIB 2-Period Crossover Polysomnography Study in Participants With Primary Insomnia (MK-4305-006) (COMPLETED) PHASE2 NCT02684136 — Suvorexant in Insomnia Co-morbid With Fibromyalgia (TERMINATED) PHASE4 NCT06679062 — Suvorexant for Treatment of AUD and PTSD (RECRUITING) PHASE2 NCT03312517 — Study to Compare the Awakening Threshold Effects of Belsomra 10 mg and 20 mg to Placebo in Non-elderly Insomniacs (COMPLETED) PHASE4 NCT01043926 — Pharmacokinetics of Suvorexant in Participants With Hepatic Insufficiency (MK-4305-017) (COMPLETED) PHASE1 NCT01097629 — Safety and Efficacy Study of Suvorexant in Participants With Primary Insomnia - Study B (MK-4305-029) (COMPLETED) PHASE3 Published literature Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review Orexin receptor antagonists in the treatment of insomnia associated with psychiatric disorders: a systematic review (Translational psychiatry, 2024) Cochrane review Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis (Arquivos de neuro-psiquiatria, 2023) Cochrane review The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials (Drugs, 2023) 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-analysis (Lancet (London, England), 2022) Meta-analysis Comparative efficacy and safety of daridorexant, lemborexant, and suvorexant for insomnia: a systematic review and network meta-analysis (Translational psychiatry, 2025) Meta-analysis Association between the use of orexin receptor antagonists and falls or fractures: A meta-analysis (Journal of psychiatric research, 2024) 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 hypnotics (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2024) Meta-analysis Clinical safety and narcolepsy-like symptoms of dual orexin receptor antagonists in patients with insomnia: a systematic review and meta-analysis (Sleep, 2024) Systematic review Efficacy and safety profiles of FDA-approved dual orexin receptor antagonists in depression: A systematic review of pre-clinical and clinical studies (Journal of psychiatric research, 2025) Systematic review The putative effects of orexin receptor antagonists on pain and sleep in humans: A systematic review (Sleep medicine, 2025) Clinical trial publication Smartphone-Based Real-Time Assessment of Daytime Insomnia Symptoms With Suvorexant: A Randomized Clinical Trial (JAMA network open, 2026) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
TEMAZEPAM	Small molecule	Approved	Strong	100	6 trials 4 Cochrane 5 Meta-analysis 61 Trial pubs 38 RCT View evidence Registry trials NCT01519544 — Comparison of Temazepam and Acetazolamide to Treat Difficulty Sleeping at High Altitude (COMPLETED) NA NCT03928301 — Efficacy of Wholetones® 2Sleep Music on Health and Sleep Behaviors of Healthy Adults With Insomnia Symptoms (COMPLETED) NA NCT00245661 — Effects of Temazepam in Patients With Chronic Pulmonary Obstructive Disease (COMPLETED) PHASE3 NCT00940550 — Study to Investigate the Effects of Melatonin, Temazepam & Zolpidem on Sleep EEG in Men and Women (COMPLETED) PHASE1 NCT00465972 — The Treatment of Insomnia in Patients With HIV Disease (COMPLETED) PHASE4 NCT02153788 — Efficacy and Safety of Temazepam in HIV Seropositive Patients With Insomnia (COMPLETED) PHASE4 Published literature Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews (Systematic reviews, 2019) Cochrane review Insomnia in the elderly (BMJ clinical evidence, 2007) Cochrane review Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis (Human psychopharmacology, 2004) Meta-analysis Comparative efficacy and safety of hypnotics for insomnia in older adults: a systematic review and network meta-analysis (Sleep, 2021) Meta-analysis Pharmacological agents for improving sleep quality at high altitude: a systematic review and meta-analysis of randomized controlled trials (Sleep medicine, 2018) Meta-analysis Toward evidence-based prescribing at end of life: a comparative review of temazepam and zolpidem for the treatment of insomnia (The American journal of hospice & palliative care, 2003) Clinical trial publication Masked Taper With Behavioral Intervention for Discontinuation of Benzodiazepine Receptor Agonists: A Randomized Clinical Trial (JAMA internal medicine, 2024) Clinical trial publication Temazepam or Melatonin Versus Placebo for the Treatment of Insomnia in Advanced Cancer: A Three-Arm, Double-Blind, Phase III, Multicenter, Randomized Clinical Trial (Journal of palliative medicine, 2024) Clinical trial publication Withdrawal from long-term use of zopiclone, zolpidem and temazepam may improve perceived sleep and quality of life in older adults with primary insomnia (Basic & clinical pharmacology & toxicology, 2019) Clinical trial publication Long-term persistence of withdrawal of temazepam, zopiclone, and zolpidem in older adults: a 3-year follow-up study (BMC geriatrics, 2018) Clinical trial publication Handgrip strength and balance in older adults following withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotics (BMC geriatrics, 2014) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
TRIAZOLAM	Small molecule	Approved	Strong	100	1 trials 3 Cochrane 5 Meta-analysis 93 Trial pubs 55 RCT View evidence Registry trials NCT01888497 — Next-Day Residual Effects of Gabapentin, Diphenhydramine and Triazolam on Simulated Driving Performance in Normal Volunteers (COMPLETED) PHASE3 Published literature Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews (Systematic reviews, 2019) Cochrane review Insomnia in the elderly (BMJ clinical evidence, 2007) 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 trials (Psychiatry and clinical neurosciences, 2025) 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 hypnotics (European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2024) Meta-analysis Comparative efficacy and safety of hypnotics for insomnia in older adults: a systematic review and network meta-analysis (Sleep, 2021) Meta-analysis Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies (International clinical psychopharmacology, 1999) Systematic review Pharmacological treatment of insomnia in alcohol recovery: a systematic review (Alcohol and alcoholism (Oxford, Oxfordshire), 2011) Clinical trial publication Effects of different doses of triazolam in the middle-of-the-night insomnia: a double-blind, randomized, parallel group study (Journal of neurology, 2017) Clinical trial publication CAP variables and arousals as sleep electroencephalogram markers for primary insomnia (Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2003) Clinical trial publication Nighttime versus daytime hypnotic self-administration (Psychopharmacology, 2002) Clinical trial publication A double-blind, randomized and placebo-controlled study on the polysomnographic withdrawal effects of zopiclone, zolpidem and triazolam in healthy subjects (European archives of psychiatry and clinical neuroscience, 2001) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ZALEPLON	Small molecule	Approved	Strong	100	7 trials 10 Cochrane 14 Meta-analysis 14 Trial pubs 13 RCT View evidence Registry trials NCT00878553 — Study of Sleep-maintenance Activity of 3 Doses of SKP-1041 (COMPLETED) PHASE2 NCT01277107 — A Polysomnographic Study to Compare the Efficacy of Gastric Retentive Zaleplon Accordion Pill to Placebo in Subjects With Insomnia (COMPLETED) PHASE2 NCT03928301 — Efficacy of Wholetones® 2Sleep Music on Health and Sleep Behaviors of Healthy Adults With Insomnia Symptoms (COMPLETED) NA NCT00694187 — Bioequivalency Study of Zaleplon 10 mg Capsules Under Fasting Conditions (COMPLETED) NA NCT00694317 — Bioequivalency Study of Zaleplon 10 mg Capsules Under Fed Conditions (COMPLETED) NA NCT06640023 — The Study in Outpatient Medicine Using Nudges to Improve Sleep (ACTIVE_NOT_RECRUITING) NA NCT03489304 — Zaleplon in HIV Patients With Depression (COMPLETED) PHASE2 Published literature Cochrane review Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis (Sleep medicine, 2025) Cochrane review Comparative efficacy of hypnotics in young and middle-aged adults with insomnia: a systematic review and network meta-analysis (Sleep & breathing = Schlaf & Atmung, 2023) 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-analysis (Lancet (London, England), 2022) Cochrane review Pharmacological interventions for the treatment of insomnia: quantitative comparison of drug efficacy (Sleep medicine, 2020) Cochrane review Drug treatment of primary insomnia: a meta-analysis of polysomnographic randomized controlled trials (CNS drugs, 2014) Meta-analysis Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis (Sleep medicine reviews, 2023) Meta-analysis Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis (Journal of managed care & specialty pharmacy, 2021) Systematic review Clinical practice guidelines for switching or deprescribing hypnotic medications for chronic insomnia: Results of European neuropsychopharmacology and sleep expert's consensus group (Sleep medicine, 2025) 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 Harmed (The Journal of clinical psychiatry, 2021) Clinical trial publication Enhancement of zaleplon oral bioavailability using optimized self-nano emulsifying drug delivery systems and its effect on sleep quality among a sample of psychiatric patients (Drug delivery, 2019) Clinical trial publication Patient Education and Pharmacist Consultation Influence on Nonbenzodiazepine Sedative Medication Deprescribing Success for Older Adults (The Permanente journal, 2019) Clinical trial publication A double-blind, randomized, comparative study to evaluate the efficacy and safety of zaleplon versus zolpidem in shortening sleep latency in primary insomnia (Chang Gung medical journal, 2011) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ZOLPIDEM TARTRATE	Small molecule	Approved	Strong	100	8 trials 2 Meta-analysis 13 Trial pubs 13 RCT View evidence Registry trials NCT05456152 — Safety and Efficacy of Zolpidem in the Long-Term Treatment of Insomnia (UNKNOWN) PHASE3 NCT00156533 — Long Term Treatment With Zolpidem: Nightly and Intermittent Dosing (COMPLETED) PHASE4 NCT00662155 — The Role of Partial Reinforcement in the Long Term Management of Insomnia (COMPLETED) NA NCT01685073 — The Role of Sleep in the Treatment of Cannabis Use Disorders (COMPLETED) PHASE2, PHASE3 NCT07542756 — A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia (RECRUITING) PHASE4 NCT00044629 — Combined Behavioral/Pharmacological Therapy for Insomnia (COMPLETED) PHASE2 NCT02839200 — Efficacy and Safety of ACT-541468 in Adult Subjects With Insomnia Disorder (COMPLETED) PHASE2 NCT00530556 — Insomnia and Daytime Function in Osteoarthritis (COMPLETED) PHASE4 Published literature Meta-analysis Lemborexant vs suvorexant for insomnia: A systematic review and network meta-analysis (Journal of psychiatric research, 2020) Meta-analysis Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy (JAMA, 1997) Clinical trial publication Effect of lemborexant on sleep architecture in participants with insomnia disorder and mild obstructive sleep apnea (Sleep medicine, 2025) Clinical trial publication Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials (Drugs & aging, 2024) Clinical trial publication Comparison of the treatment effectiveness between lemborexant and zolpidem tartrate extended-release for insomnia disorder subtypes defined based on polysomnographic findings (Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2023) Clinical trial publication Comparison of the effect of lemborexant with placebo and zolpidem tartrate extended release on sleep architecture in older adults with insomnia disorder (Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2021) Clinical trial publication Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening (Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2020) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ALMOREXANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
AMITRIPTYLINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
BROTIZOLAM	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CANNABIDIOL	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
DEXMEDETOMIDINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
EPLIVANSERIN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
ESMIRTAZAPINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
FAZAMOREXANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
GABAPENTIN	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
ORN-0829 HYDRATE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
QUETIAPINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
SELTOREXANT	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
SERTRALINE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
TRAZODONE	Small molecule	Phase III	Moderate	85	—	Open Targets, ChEMBL	ChEMBL Open Targets
CHEMBL1059	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL1200750	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
CHEMBL2107339	Small molecule	Phase III	Moderate	80	—	ChEMBL	ChEMBL Open Targets
DARIDOREXANT	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
ESTROGEN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
GABOXADOL	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
INDIPLON	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
LORMETAZEPAM	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LUMATEPERONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
NALTREXONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
TASIMELTEON	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
TRAZODONE HYDROCHLORIDE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
VENLAFAXINE HYDROCHLORIDE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
VOLINANSERIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ZOLPIDEM	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
ZOPICLONE	Small molecule	Phase III	Moderate	80	—	Open Targets, ChEMBL	ChEMBL Open Targets
ZURANOLONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ADIPIPLON	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ARMODAFINIL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
ATAGABALIN	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
CANNABINOL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
FILOREXANT	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
LY2624803	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
MODAFINIL	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
NELOTANSERIN	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
PIROMELATINE	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
SB-649868	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
SUNOBINOP	Small molecule	Phase II	Moderate	60	—	Open Targets, ChEMBL	ChEMBL Open Targets
(-)-LIMONENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
(-)-LINALOOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ALPHA-PINENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ALPHA-TERPINENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ALPHA-TERPINEOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BENZODIAZEPINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BETA-CARYOPHYLLENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CHEMBL1201178	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL1672054	Small molecule	Phase II	Emerging	60	—	ChEMBL	ChEMBL Open Targets
CHEMBL3338865	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CITALOPRAM	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DIMDAZENIL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DOXEPIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DRONABINOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ESCITALOPRAM OXALATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FERROUS SULFATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FLUOXETINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ILOPERIDONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LINALOOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LINALOOL (+)	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
MYRCENE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
OXALOACETATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
PALIPERIDONE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
PHYTOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
PIMAVANSERIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SODIUM OXYBATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
SOLRIAMFETOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TASIPIMIDINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
TESAMORELIN	Biologic	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
FLURAZEPAM	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
PROPOFOL	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
SUNOBINOP TOSYLATE	Small molecule	Phase I	Emerging	40	—	Open Targets, ChEMBL	ChEMBL Open Targets
CHEMBL2106049	Small molecule	Phase I	Emerging	35	—	ChEMBL	ChEMBL Open Targets
CHEMBL407	Small molecule	Phase I	Emerging	35	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
PIPAMPERONE	Small molecule	Phase I	Emerging	35	—	Open Targets	ChEMBL Open Targets
AMOBARBITAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
APROBARBITAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BARBITAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUTABARBITAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
BUTETHAL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CARPHENAZINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CHEMBL25	Small molecule	Preclinical	Emerging	15	—	ChEMBL	ChEMBL Open Targets
CIPEPOFOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CLONAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
CLONIDINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
DIAZEPAM	Small molecule	Preclinical	Emerging	15	2 Cochrane 3 Meta-analysis 18 Trial pubs 10 RCT View evidence Published literature Cochrane review Auricular acupuncture treatment for insomnia: a systematic review (Journal of alternative and complementary medicine (New York, N.Y.), 2007) Cochrane review Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis (Human psychopharmacology, 2004) Meta-analysis Auricular acupuncture for insomnia: a systematic review (International journal of clinical practice, 2008) Systematic review Melatonin and melatonin agonists as treatments for benzodiazepines and hypnotics withdrawal in patients with primary insomnia. A systematic review (Drug and alcohol dependence, 2020) Clinical trial publication Masked Taper With Behavioral Intervention for Discontinuation of Benzodiazepine Receptor Agonists: A Randomized Clinical Trial (JAMA internal medicine, 2024) Clinical trial publication Therapeutic Efficacy of Head Gusha Combined with Kaitianmen in the Management of Insomnia (Alternative therapies in health and medicine, 2024) Clinical trial publication [Impacts of the repetitive transcranial acupuncture stimulation on the content of serum orexin A in patients with post-stroke insomnia] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2018) Clinical trial publication [Clinical observation of "Yinqi Guiyuan needles therapy" combined with moxibustion at Yongquan (KI 1) on perimenopausal insomnia with heart-kidney imbalance] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2018) Clinical trial publication Nefazodone in major depression: adjunctive benzodiazepine therapy and tolerability (Journal of clinical psychopharmacology, 1998) Randomized controlled trial A double-blind group comparative study using the new anti-depressant Org 3770, placebo and diazepam in patients with expected insomnia and anxiety before elective gynaecological surgery (Acta psychiatrica Scandinavica, 1985) CT.gov search · Cochrane · PubMed	Open Targets	ChEMBL Open Targets
DYDROGESTERONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ELEUTHERO	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ESCITALOPRAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ESTRADIOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ETHCHLORVYNOL	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
ETHINAMATE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUNITRAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
FLUVOXAMINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
GLUTETHIMIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LIDOCAINE HYDROCHLORIDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
LORAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MAGNESIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
METHAQUALONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
METHYPRYLON	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
MIDAZOLAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NABILONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
NITRAZEPAM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
OBETICHOLIC ACID	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PARALDEHYDE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PRAZOSIN	Small molecule	Preclinical	Emerging	15	1 trials 2 Meta-analysis 3 Trial pubs 3 RCT View evidence Registry trials NCT00393874 — Efficacy of Sleep Interventions for Posttraumatic Stress Disorder (PTSD) (COMPLETED) NA Published literature Meta-analysis Factors impacting prazosin efficacy for nightmares and insomnia in PTSD patients - a systematic review and meta-regression analysis (Progress in neuro-psychopharmacology & biological psychiatry, 2025) Meta-analysis Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis (Sleep medicine, 2024) Clinical trial publication A Pilot, Randomized Clinical Trial of Bedtime Doses of Prazosin Versus Placebo in Suicidal Posttraumatic Stress Disorder Patients With Nightmares (Journal of clinical psychopharmacology, 2018) Clinical trial publication Prazosin for Veterans with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence: A Clinical Trial (Alcoholism, clinical and experimental research, 2016) Clinical trial publication Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study (Biological psychiatry, 2008) CT.gov search · Cochrane · PubMed	Open Targets	ChEMBL Open Targets
PROGESTERONE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
PROPIOMAZINE	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
TRICLOFOS SODIUM	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets
VALERIAN	Small molecule	Preclinical	Emerging	15	—	Open Targets	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
ACEBUTOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETAZOLAMIDE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ADUCANUMAB Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
AMPHETAMINE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
APIXABAN Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
APOMORPHINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
APRACLONIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ASENAPINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATIPAMEZOLE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
BENZPHETAMINE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
BEPRIDIL Repurposing via CACNA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
BEPRIDIL HYDROCHLORIDE Repurposing via CACNA1A	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BETAXOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BETHANIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BICALUTAMIDE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BISOPROLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BRIMONIDINE TARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BROMOCRIPTINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
BUPROPION HYDROCHLORIDE Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
CABERGOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CARBACHOL Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CARVEDILOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CELECOXIB Repurposing via CACNA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
CELIPROLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CHLORPROMAZINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
CHOLESTEROL Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
CHORIOGONADOTROPIN ALFA Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
CIPROFLOXACIN Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLOMIPRAMINE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLONIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	3 trials View evidence Registry trials NCT04278404 — Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) (RECRUITING) NCT05618002 — Lemborexant vs Zopiclone vs Clonidine for Insomnia Treatment in Chronic Pain Patients (RECRUITING) NCT05277038 — Clonidine is Better Than Zopiclone for Insomnia Treatment in Chronic Pain Patients (COMPLETED) CT.gov search · Cochrane · PubMed	DGIdb	—
CYCLOBENZAPRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DEBRISOQUIN Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXMEDETOMIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DEXTROAMPHETAMINE SULFATE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing via ADCY2	Small molecule	Approved	Strong	95	2 Cochrane 3 Meta-analysis 18 Trial pubs 10 RCT View evidence Published literature Cochrane review Auricular acupuncture treatment for insomnia: a systematic review (Journal of alternative and complementary medicine (New York, N.Y.), 2007) Cochrane review Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis (Human psychopharmacology, 2004) Meta-analysis Auricular acupuncture for insomnia: a systematic review (International journal of clinical practice, 2008) Systematic review Melatonin and melatonin agonists as treatments for benzodiazepines and hypnotics withdrawal in patients with primary insomnia. A systematic review (Drug and alcohol dependence, 2020) Clinical trial publication Masked Taper With Behavioral Intervention for Discontinuation of Benzodiazepine Receptor Agonists: A Randomized Clinical Trial (JAMA internal medicine, 2024) Clinical trial publication Therapeutic Efficacy of Head Gusha Combined with Kaitianmen in the Management of Insomnia (Alternative therapies in health and medicine, 2024) Clinical trial publication [Impacts of the repetitive transcranial acupuncture stimulation on the content of serum orexin A in patients with post-stroke insomnia] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2018) Clinical trial publication [Clinical observation of "Yinqi Guiyuan needles therapy" combined with moxibustion at Yongquan (KI 1) on perimenopausal insomnia with heart-kidney imbalance] (Zhongguo zhen jiu = Chinese acupuncture & moxibustion, 2018) Clinical trial publication Nefazodone in major depression: adjunctive benzodiazepine therapy and tolerability (Journal of clinical psychopharmacology, 1998) Randomized controlled trial A double-blind group comparative study using the new anti-depressant Org 3770, placebo and diazepam in patients with expected insomnia and anxiety before elective gynaecological surgery (Acta psychiatrica Scandinavica, 1985) CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
DICHLORPHENAMIDE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIETHYLSTILBESTROL Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIPIVEFRIN Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
DIPIVEFRIN HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
DONANEMAB Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
DONEPEZIL Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
DOPAMINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
DOXAZOSIN MESYLATE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
DROXIDOPA Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
EPHEDRINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPHEDRINE SULFATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPINEPHRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
EPINEPHRINE BITARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
EPIRUBICIN Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ERGOLOID MESYLATES Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ERGOLOID MESYLATES, USP Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
ERGOTAMINE TARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ESMOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ETHOXZOLAMIDE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ETOMIDATE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOFIBRATE MICRONIZED Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOLDOPAM Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUMAZENIL Repurposing via ADCY2	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
FLUTICASONE Repurposing via CA10	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUVASTATIN Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
GABAPENTIN Repurposing via CACNA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
GABAPENTIN ENACARBIL Repurposing via CACNA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
GALANTAMINE Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
GANCICLOVIR Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
GUANABENZ ACETATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
GUANFACINE HYDROCHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
HYDROXYAMPHETAMINE HYDROBROMIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ILOPERIDONE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
IMIPRAMINE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDAPAMIDE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
INDOMETHACIN Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
IRBESARTAN Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
ISOPROTERENOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
ISOSORBIDE DINITRATE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
LABETALOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
LABETALOL HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LECANEMAB Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
LEVONORDEFRIN Repurposing via ADRA2C	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
LITHIUM CATION Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
LOFEXIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
LORAZEPAM Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
LURASIDONE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
LUTEIN Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
MAFENIDE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MECAMYLAMINE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MEPERIDINE HYDROCHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
MEPHENTERMINE SULFATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METHAMPHETAMINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
METHAZOLAMIDE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHOXSALEN Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
METHYLDOPA ANHYDROUS Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
METHYLDOPATE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
METOPROLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
METOPROLOL Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MIANSERIN Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
MILNACIPRAN Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
MIRTAZAPINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
MONTELUKAST SODIUM Repurposing via CA10	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXISYLYTE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
MOXONIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NADOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	1 pubs View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
NALIDIXIC ACID Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NAPHAZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NAPHAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NEBIVOLOL HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NICOTINE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NICOTINE POLACRILEX Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
NISOLDIPINE Repurposing via CACNA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
NOREPINEPHRINE BITARTRATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
NORETHINDRONE ACETATE Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
NORFLOXACIN Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
NORTRIPTYLINE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
OFLOXACIN Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
OLANZAPINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
OXYMETAZOLINE HYDROCHLORIDE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PERGOLIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENOXYBENZAMINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENTOLAMINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENTOLAMINE MESYLATE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
PHENYLPROPANOLAMINE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
PHENYTOIN Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
PINDOLOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAVASTATIN SODIUM Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PRAZOSIN Repurposing via ADCY2	Small molecule	Approved	Strong	95	1 trials 2 Meta-analysis 3 Trial pubs 3 RCT View evidence Registry trials NCT00393874 — Efficacy of Sleep Interventions for Posttraumatic Stress Disorder (PTSD) (COMPLETED) NA Published literature Meta-analysis Factors impacting prazosin efficacy for nightmares and insomnia in PTSD patients - a systematic review and meta-regression analysis (Progress in neuro-psychopharmacology & biological psychiatry, 2025) Meta-analysis Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis (Sleep medicine, 2024) Clinical trial publication A Pilot, Randomized Clinical Trial of Bedtime Doses of Prazosin Versus Placebo in Suicidal Posttraumatic Stress Disorder Patients With Nightmares (Journal of clinical psychopharmacology, 2018) Clinical trial publication Prazosin for Veterans with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence: A Clinical Trial (Alcoholism, clinical and experimental research, 2016) Clinical trial publication Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study (Biological psychiatry, 2008) CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
PREDNISONE Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
PREGABALIN Repurposing via CACNA1A	Small molecule	Approved	Strong	95	—	DGIdb	—
PROPRANOLOL HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
PROPYLHEXEDRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
PSEUDOEPHEDRINE POLISTIREX Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
RACEPINEPHRINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
RAUWOLFIA SERPENTINA Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
RAUWOLFIA SERPENTINA (USP) Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
REMIFENTANIL HYDROCHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
RILMENIDINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
RISPERIDONE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
RITONAVIR Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
RIVASTIGMINE Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
SIROLIMUS Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
SODIUM CHLORIDE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
SOTALOL Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
SULBACTAM Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
SULOCTIDIL Repurposing via CACNA1A	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TACROLIMUS ANHYDROUS Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TAZOBACTAM Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
TERODILINE HYDROCHLORIDE Repurposing via CACNA1A	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TETRAHYDROZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
TETRAHYDROZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TIZANIDINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
TIZANIDINE HYDROCHLORIDE Repurposing via ADRA2B	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TOLAZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
TOLAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
TRAZODONE Repurposing via ADRA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
TRETINOIN Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
TRIAMCINOLONE Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
TROGLITAZONE Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
TROGLITAZONE Repurposing via ADCY2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
XYLAZINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	—
XYLOMETAZOLINE HYDROCHLORIDE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
YOHIMBINE Repurposing via ADRA2C	Small molecule	Approved	Strong	95	1 Meta-analysis View evidence Published literature Meta-analysis Herbal medications for common ailments in the elderly (Drugs & aging, 1999) CT.gov search · Cochrane · PubMed	DGIdb	—
DARAPLADIB Repurposing via ADCY2	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
FENRETINIDE Repurposing via ADCY2	Small molecule	Phase III	Moderate	70	—	ChEMBL	ChEMBL Open Targets
CHEMBL:CHEMBL401844 Repurposing via ADCY2	Small molecule	Phase II	Emerging	50	—	DGIdb	ChEMBL Open Targets
FD1 Repurposing via ADCY2	Small molecule	Phase II	Emerging	50	—	DGIdb	—
SKF-83566 Repurposing via ADCY2	Small molecule	Phase II	Emerging	50	—	DGIdb	—
ALPRENOLOL Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
AMIFLOXACIN Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
BROLAMFETAMINE Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
CARZENIDE Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIFLOXACIN Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
DIMECAMINE Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ELLAGIC ACID Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ENISOPROST Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FENCAMFAMIN Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
FLEROXACIN Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
IDOXIFENE Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
LYSERGIDE Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
MERAFLOXACIN Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
TENAMFETAMINE Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets
ZIDAPAMIDE Repurposing via ADCY2	Small molecule	Phase II	Emerging	45	—	ChEMBL	ChEMBL Open Targets

Natural Products

101 natural products with the same evidence schema as repurposed drugs — registry trials, PubMed literature, and reference links (pipeline-ranked). Only agents with direct clinical evidence are shown by default.

Reference lookups: Examine.com

Show agents without direct trial evidence

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
Probiotics Natural product Clinical trial publication Efficacy of probiotic supplements in improving the symptoms of psychosi… Clinical trial publication Bifidobacterium breve CCFM1025 Improves Sleep Quality via Regulating th… Human Study Daily consumption of Lactobacillus plantarum PS128 as a dietary supplem…	Probiotic	Phase II	Moderate	26	8 trials 2 Trial pubs View evidence Registry trials NCT04167475 — Effect of B. Longum 1714™ on Sleep Quality (COMPLETED) PHASE2 NCT03932474 — EVALUATION OF EFFICACY OF SAMEUP IN SUBJECTS WITH DEPRESSION SYMPTOMS: A RANDOMIZED STUDY (COMPLETED) NA NCT06789718 — Impact of GABA Probiotic Lactiplantibacillus Plantarum Lp815 on Sleep Outcomes in Participants with Self-Reported Sleep Disturbance (ACTIVE_NOT_RECRUITING) NCT05917379 — The Efficacy and Safty of FMT in Patients With CID (COMPLETED) PHASE1, PHASE2 NCT05717972 — Effects of Kombucha Intervention on Emotional Distress and Sleep Quality in Breast Cancer Survivors (UNKNOWN) NA NCT06486064 — Evaluating the Potential of Probiotic Supplementation Sleep Quality (COMPLETED) NA NCT07410052 — Microbiome-Targeted Enhancement of Neurocognition With Probiotics-Riboflavin Combination (NOT_YET_RECRUITING) NA NCT06361368 — Efficacy Assessment of Probiotics in Improving Sleep Indices (UNKNOWN) NA Published literature Clinical trial publication Efficacy of probiotic supplements in improving the symptoms of psychosis, anxiety, insomnia, and anorexia due to amphetamine and methamphetamine use: a randomized clinical trial (Psychopharmacology, 2024) Clinical trial publication Bifidobacterium breve CCFM1025 Improves Sleep Quality via Regulating the Activity of the HPA Axis: A Randomized Clinical Trial (Nutrients, 2023) CT.gov search · Cochrane · PubMed	ClinicalTrials.gov, Examine.com	Examine.com
Magnesium Natural product Human Study Supplementation of magnesium appears to improve subjective measures of… Human Study These findings support the hypothesis that migraine is a consequence of… Animal Study Nitric oxide modulation is involved in the protective effect of curcumi…	Nutraceutical	Phase III	Moderate	20	8 trials View evidence Registry trials NCT05368909 — Clinical Study to Assess a Dietary Supplement on Sleep Health and Quality (COMPLETED) NA NCT05521243 — An Exploratory Investigation of a Supplement to Enhance Sleep Quality and Quantity (COMPLETED) NA NCT07515417 — Effect of Magnesium Supplementation on Sleep Quality and Cognitive Function in Saudi Adults (ACTIVE_NOT_RECRUITING) NA NCT04642313 — Comparison of Mg Vs. K Supplementation on Insomnia in Diabetics (UNKNOWN) NA NCT04167475 — Effect of B. Longum 1714™ on Sleep Quality (COMPLETED) PHASE2 NCT00833092 — Magnesium Nutrition and Sleep Behavior in Older Adults (COMPLETED) NA NCT05825209 — Effectiveness of Food-grown Magnesium on Sleep Quality/Quantity (COMPLETED) PHASE3 NCT02883790 — Effects of Somnage® in the Management on Sleep and Mood in Cancer Patients (TERMINATED) NA CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Valerian Natural product Human Study A combination of valerian and hops reduces sleep latency in patients su… Human Study Effects of valerian on subjective sedation, field sobriety testing and… Human Study Kava and valerian root are effective in the treatment of stress-induced…	Botanical	Phase III	Moderate	17	7 trials 18 RCT View evidence Registry trials NCT00070928 — Valerian to Improve Sleep in Patients With Parkinson's Disease (COMPLETED) PHASE2 NCT00997256 — Study to Investigate Effects of a Herbal Drug Compared to Placebo on Sleep (COMPLETED) PHASE1 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 (UNKNOWN) PHASE3 NCT05459272 — Clinical Trial on a Food Supplement With Melatonin and Herbal Products to Improve Sleep Quality (UNKNOWN) NA NCT05609890 — Novel Formulation for Sleep Among People With Poor Sleep Quality (COMPLETED) NA NCT07200167 — Study of the Efficacy of Dietary Supplementation in Targeting Sleep Quality (NutriSom-01B) (NOT_YET_RECRUITING) NA NCT05185219 — The Effect of Valerian on Insomnia in Menopausal Women (UNKNOWN) NA CT.gov search · Cochrane · PubMed	Examine.com	Examine.com
Passionflower Natural product Human Study Consumption of medical Cannabis flower is associated with significant i… Human Study The current study demonstrated the positive effects of passionflower on… Human Study This pilot study suggests that the combination of melatonin, vitamin B6…	Botanical	Phase III	Moderate	17	4 trials 1 Cochrane View evidence Registry trials NCT00997256 — Study to Investigate Effects of a Herbal Drug Compared to Placebo on Sleep (COMPLETED) PHASE1 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 (UNKNOWN) PHASE3 NCT05459272 — Clinical Trial on a Food Supplement With Melatonin and Herbal Products to Improve Sleep Quality (UNKNOWN) NA NCT06278077 — Neurexan - a Clinical Trial in Short-Term Insomnia Patients (COMPLETED) PHASE2 CT.gov search · Cochrane · PubMed	Examine.com	Examine.com
Melatonin Natural product Clinical trial publication Sleep aid usage following benzodiazepine receptor agonist tapering and… Clinical trial publication Effects of bright light and near-infrared light on insomnia symptoms in… Clinical trial publication Efficacy of clonidine and melatonin for treating insomnia in anxious ch…	Nutraceutical	Approved	Moderate	17	8 trials 26 Cochrane 137 Trial pubs 107 RCT View evidence Registry trials NCT05368909 — Clinical Study to Assess a Dietary Supplement on Sleep Health and Quality (COMPLETED) NA NCT06802913 — A Novel Inhaled Formulation of Melatonin to Treat Adults With Insomnia: Efficacy Study (RECRUITING) EARLY_PHASE1 NCT05521243 — An Exploratory Investigation of a Supplement to Enhance Sleep Quality and Quantity (COMPLETED) NA NCT03461042 — The Study of Combination Use of Melatonin Receptor Agonist for Dose Reduction or Interruptions of Benzodiazepine (BZD) and Non-BZD Hypnotics on Chronic Insomnia (COMPLETED) PHASE4 NCT02431728 — The Effect of Melatonin Upon Post-Acute Withdrawal Among Males in a Residential Treatment Program (COMPLETED) PHASE1, PHASE2 NCT02940769 — Neurobiological Effects of Light on MDD (TERMINATED) NA NCT04642313 — Comparison of Mg Vs. K Supplementation on Insomnia in Diabetics (UNKNOWN) NA NCT05324267 — Determinants of Sleep Quality in Spanish Population (SSQD Study) (COMPLETED) Published literature Clinical trial publication Sleep aid usage following benzodiazepine receptor agonist tapering and cognitive behavioral therapy for insomnia in middle-aged and older adults (Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2026) Clinical trial publication Effects of bright light and near-infrared light on insomnia symptoms in community-dwelling older adults: a randomized clinical trial (Photodiagnosis and photodynamic therapy, 2026) Clinical trial publication Efficacy of clonidine and melatonin for treating insomnia in anxious children: a randomized comparison (BMC pediatrics, 2026) Clinical trial publication Heat-Treated Limosilactobacillus fermentum PS150 Improves Sleep Quality with Severity-Dependent Benefits: A Randomized, Placebo-Controlled Trial (Nutrients, 2025) Clinical trial publication A Pilot Randomised Controlled Trial of Sublingual Melatonin for Sleep Onset Insomnia in Children With Foetal Alcohol Spectrum Disorder (FASD) (Journal of paediatrics and child health, 2026) CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Ashwagandha Natural product Meta Analysis, Review Ashwagandha extract appears to has a beneficial effect in improving sle… Human Study Ashwagandha could be of potential use to improve sleep parameters in pa… Animal Study Ashwagandha may serve as an effective dietary supplement for management…	Ayurvedic	Preclinical	Moderate	17	6 trials 1 RCT View evidence Registry trials NCT05368909 — Clinical Study to Assess a Dietary Supplement on Sleep Health and Quality (COMPLETED) NA NCT06154616 — Efficacy of Different Types of Milk in Improving Sleep Quality in Subjects With Sleep Problems (Milca) (COMPLETED) NA NCT06900569 — Ashwagandha Supplementation for Prevention of Muscle Damage (COMPLETED) NA NCT07461402 — Plant Protein With Ashwagandha-Rhodiola for Sleep Quality (COMPLETED) NA NCT07085819 — Sleep Promoting Properties of a Botanical Extract in a Population Complaining From Non-Restorative Sleep (NRS) (RECRUITING) NA NCT07441070 — Effect of Ashwagandha Root Extract on Stress, Anxiety, and Sleep Quality in Adults Experiencing Minority Stress (RECRUITING) NA CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Melatonin Natural product Clinical trial publication Sleep aid usage following benzodiazepine receptor agonist tapering and… Clinical trial publication Effects of bright light and near-infrared light on insomnia symptoms in… Clinical trial publication Efficacy of clonidine and melatonin for treating insomnia in anxious ch…	Nutraceutical	Approved	Emerging	16	8 trials 26 Cochrane 137 Trial pubs 107 RCT View evidence Registry trials NCT05368909 — Clinical Study to Assess a Dietary Supplement on Sleep Health and Quality (COMPLETED) NA NCT06802913 — A Novel Inhaled Formulation of Melatonin to Treat Adults With Insomnia: Efficacy Study (RECRUITING) EARLY_PHASE1 NCT05521243 — An Exploratory Investigation of a Supplement to Enhance Sleep Quality and Quantity (COMPLETED) NA NCT03461042 — The Study of Combination Use of Melatonin Receptor Agonist for Dose Reduction or Interruptions of Benzodiazepine (BZD) and Non-BZD Hypnotics on Chronic Insomnia (COMPLETED) PHASE4 NCT02431728 — The Effect of Melatonin Upon Post-Acute Withdrawal Among Males in a Residential Treatment Program (COMPLETED) PHASE1, PHASE2 NCT02940769 — Neurobiological Effects of Light on MDD (TERMINATED) NA NCT04642313 — Comparison of Mg Vs. K Supplementation on Insomnia in Diabetics (UNKNOWN) NA NCT05324267 — Determinants of Sleep Quality in Spanish Population (SSQD Study) (COMPLETED) Published literature Clinical trial publication Sleep aid usage following benzodiazepine receptor agonist tapering and cognitive behavioral therapy for insomnia in middle-aged and older adults (Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2026) Clinical trial publication Effects of bright light and near-infrared light on insomnia symptoms in community-dwelling older adults: a randomized clinical trial (Photodiagnosis and photodynamic therapy, 2026) Clinical trial publication Efficacy of clonidine and melatonin for treating insomnia in anxious children: a randomized comparison (BMC pediatrics, 2026) Clinical trial publication Heat-Treated Limosilactobacillus fermentum PS150 Improves Sleep Quality with Severity-Dependent Benefits: A Randomized, Placebo-Controlled Trial (Nutrients, 2025) Clinical trial publication A Pilot Randomised Controlled Trial of Sublingual Melatonin for Sleep Onset Insomnia in Children With Foetal Alcohol Spectrum Disorder (FASD) (Journal of paediatrics and child health, 2026) CT.gov search · Cochrane · PubMed	ClinicalTrials.gov, Examine.com	PubChem Examine.com
Ginkgo Biloba Natural product Ginkgo biloba for tinnitus Medicinal herbs for the treatment of anxiety: A systematic review and n… GABA-modulating phytomedicines for anxiety: A systematic review of prec…	Botanical	Preclinical	Moderate	12	1 Cochrane View evidence CT.gov search · Cochrane · PubMed	Examine.com	Examine.com
Magnesium Natural product Human Study Supplementation of magnesium appears to improve subjective measures of… Animal Study Nitric oxide modulation is involved in the protective effect of curcumi…	Nutraceutical	Phase III	Emerging	10	8 trials View evidence Registry trials NCT05368909 — Clinical Study to Assess a Dietary Supplement on Sleep Health and Quality (COMPLETED) NA NCT05521243 — An Exploratory Investigation of a Supplement to Enhance Sleep Quality and Quantity (COMPLETED) NA NCT07515417 — Effect of Magnesium Supplementation on Sleep Quality and Cognitive Function in Saudi Adults (ACTIVE_NOT_RECRUITING) NA NCT04642313 — Comparison of Mg Vs. K Supplementation on Insomnia in Diabetics (UNKNOWN) NA NCT04167475 — Effect of B. Longum 1714™ on Sleep Quality (COMPLETED) PHASE2 NCT00833092 — Magnesium Nutrition and Sleep Behavior in Older Adults (COMPLETED) NA NCT05825209 — Effectiveness of Food-grown Magnesium on Sleep Quality/Quantity (COMPLETED) PHASE3 NCT02883790 — Effects of Somnage® in the Management on Sleep and Mood in Cancer Patients (TERMINATED) NA CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Lavender Natural product Human Study Aromatherapy massage may have some value in a hospice setting for reduc… Human Study Essential oil of lavender serves as a mild sedative and promotes deep s… Human Study Lavender fragrance had a beneficial effect on insomnia and depression i…	Nutraceutical	Preclinical	Moderate	10	8 trials View evidence Registry trials NCT05368909 — Clinical Study to Assess a Dietary Supplement on Sleep Health and Quality (COMPLETED) NA NCT05288244 — The Effect of Foot Bath and Lavender Oil Sniffing on the Severity of Insomnia in Cancer Patients (UNKNOWN) NA NCT05987020 — Effects of Aromatherapy for Older Adults at Risk of Metabolic Syndrome in the Community (UNKNOWN) NA NCT05403515 — Aromatherapy and Foot Massage on Happiness, Sleep Quality, and Fatigue Levels of Patients With Stroke (COMPLETED) NA NCT06380933 — The Effects of Receiving Warm Footbath With Lavender Essential Oil on Sleep and Comfort (COMPLETED) NA NCT03304938 — Lavender Aromatherapy on Sleep Quality and Metabolic Parameters of Type 2 Diabetic Patients With Insomnia (COMPLETED) NA NCT06774599 — Effects of Nonpharmacological Interventions in Sleep Quality, Anxiety, and Delirium for Patients of Adult Intensive Care Units (NOT_YET_RECRUITING) NA NCT02445378 — Aromatherapy and Essential Oils in Improving Insomnia and Other Symptoms in Patients With Newly Diagnosed Acute Leukemia Undergoing Chemotherapy (COMPLETED) NA CT.gov search · Cochrane · PubMed	Examine.com	Examine.com
Lemon Balm Natural product Clinical trial publication Effect of a nutraceutical combination on sleep quality among people wit… Human Study This pilot study suggests that the combination of melatonin, vitamin B6…	Nutraceutical	Preclinical	Moderate	10	3 trials 1 Trial pubs View evidence Registry trials NCT05422599 — Enhancement of Sleep Quality and Mood Following Supplementation With Lemon Balm in an Adult Population (Lemslp) (COMPLETED) NA NCT05602688 — Melissa Officinalis L. Supplementation for Emotional Health and Sleep Disturbance (COMPLETED) NA NCT05609890 — Novel Formulation for Sleep Among People With Poor Sleep Quality (COMPLETED) NA Published literature Clinical trial publication Effect of a nutraceutical combination on sleep quality among people with impaired sleep: a randomised, placebo-controlled trial (Scientific reports, 2024) CT.gov search · Cochrane · PubMed	Examine.com	Examine.com
Vitamin E Natural product Randomized controlled trial Effect of Vitamin E Supplementation on Chronic Insomnia Disorder in Pos… Human Study Low serum 25-hydroxyvitamin D concentrations in chronic insomnia patien… Human Study This pilot study suggests that the combination of melatonin, vitamin B6…	Nutraceutical	Preclinical	Emerging	10	2 trials 1 RCT View evidence Registry trials NCT03985228 — Nutritional Trial With Probiotic Fortified Milk in Women Affected by Insomnia (COMPLETED) NA NCT06146712 — A Single-Group Study to Examine the Efficacy of a Melatonin Lotion With Magnesium to Improve Sleep Quality and Quantity (COMPLETED) NA Published literature Randomized controlled trial Effect of Vitamin E Supplementation on Chronic Insomnia Disorder in Postmenopausal Women: A Prospective, Double-Blinded Randomized Controlled Trial (Nutrients, 2023) CT.gov search · Cochrane · PubMed		PubChem
Vitamin D3 Natural product Human Study Effect of vitamin E supplementation on chronic insomnia disorder in pos… Human Study Low serum 25-hydroxyvitamin D concentrations in chronic insomnia patien… Human Study This pilot study suggests that the combination of melatonin, vitamin B6…	Nutraceutical	Phase III	Emerging	10	2 trials View evidence Registry trials NCT07649824 — Isokinetic Muscle Strength, Torque, Ultrasonographic Muscle Thickness in Fibromyalgia Syndrome: A Case-Control Study (COMPLETED) NCT07644520 — Vitamin D in Diabetic Neuropathy (NOT_YET_RECRUITING) PHASE2, PHASE3 CT.gov search · Cochrane · PubMed		PubChem
Vitamin C Natural product Human Study Effect of vitamin E supplementation on chronic insomnia disorder in pos… Human Study Low serum 25-hydroxyvitamin D concentrations in chronic insomnia patien… Human Study This pilot study suggests that the combination of melatonin, vitamin B6…	Nutraceutical	Preclinical	Emerging	10	2 trials View evidence Registry trials NCT03985228 — Nutritional Trial With Probiotic Fortified Milk in Women Affected by Insomnia (COMPLETED) NA NCT05332717 — TKA Melatonin and Sleep Quality (COMPLETED) NA CT.gov search · Cochrane · PubMed		PubChem
Ashwagandha Natural product Meta Analysis, Review Ashwagandha extract appears to has a beneficial effect in improving sle… Human Study Ashwagandha could be of potential use to improve sleep parameters in pa… Animal Study Ashwagandha may serve as an effective dietary supplement for management…	Ayurvedic	Preclinical	Emerging	7	6 trials 1 RCT View evidence Registry trials NCT05368909 — Clinical Study to Assess a Dietary Supplement on Sleep Health and Quality (COMPLETED) NA NCT06154616 — Efficacy of Different Types of Milk in Improving Sleep Quality in Subjects With Sleep Problems (Milca) (COMPLETED) NA NCT06900569 — Ashwagandha Supplementation for Prevention of Muscle Damage (COMPLETED) NA NCT07461402 — Plant Protein With Ashwagandha-Rhodiola for Sleep Quality (COMPLETED) NA NCT07085819 — Sleep Promoting Properties of a Botanical Extract in a Population Complaining From Non-Restorative Sleep (NRS) (RECRUITING) NA NCT07441070 — Effect of Ashwagandha Root Extract on Stress, Anxiety, and Sleep Quality in Adults Experiencing Minority Stress (RECRUITING) NA CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Tryptophan Natural product Cochrane review A systematic review of insomnia and complementary medicine Human Study Protein source tryptophan versus pharmaceutical grade tryptophan as an… Human Study Tryptophan-rich gourd seeds significantly improve subjective and object…	Amino acid	Preclinical	Emerging	7	5 trials 1 Cochrane 22 Trial pubs 10 RCT View evidence Registry trials NCT03288077 — Nutrients to Enhance Sleep Quality and Quantity (COMPLETED) NA NCT06154616 — Efficacy of Different Types of Milk in Improving Sleep Quality in Subjects With Sleep Problems (Milca) (COMPLETED) NA NCT07461402 — Plant Protein With Ashwagandha-Rhodiola for Sleep Quality (COMPLETED) NA NCT04078724 — Impact of Nutritional Supplementation on Sleep Quality and Gut Microbiome Composition in Older Adults (COMPLETED) NA NCT05032729 — Nutritional Intervention to Enhance Sleep Quality and Quantity in Athletes (COMPLETED) NA Published literature Cochrane review A systematic review of insomnia and complementary medicine (Sleep medicine reviews, 2011) CT.gov search · Cochrane · PubMed		PubChem
Saffron Natural product Animal Study Crocin and crocetin significantly increased the total time of non-rapid… Animal Study Crocin could attenuate hyperalgesia induced by sleep deprivation.	Botanical	Preclinical	Emerging	7	5 trials 4 Trial pubs View evidence Registry trials NCT04750681 — Evaluation of the Effects of Saffron Extract on Sleep Quality and Stress (COMPLETED) NA NCT05315986 — Exploration of Relationships Between Sleep, Gut Health and Cognition (UNKNOWN) NA NCT07497698 — Saffron Extract Supplementation and Sleep Quality in Middle-Aged Adults (RECRUITING) NA NCT05609890 — Novel Formulation for Sleep Among People With Poor Sleep Quality (COMPLETED) NA NCT05690126 — Effect of Saffron Extract Supplementation on Emotional Well-being Alterations (UNKNOWN) NA CT.gov search · Cochrane · PubMed		PubChem
Cordyceps Natural product Human Study Effectiveness of fermentation broth of Cordyceps sinensis for primary i…	Mushroom	Preclinical	Emerging	7	No indexed hits View evidence CT.gov search · Cochrane · PubMed		—
L-Theanine Natural product Randomized controlled trial Effect of a nutraceutical combination on sleep quality among people wit… Randomized controlled trial L-theanine in the adjunctive treatment of generalized anxiety disorder:… Human Study The hypnotic efficacy of oral melatonin 3 mg was better than oral L-the…	Amino acid	Phase II	Emerging	7	6 trials 2 RCT View evidence Registry trials NCT05521243 — An Exploratory Investigation of a Supplement to Enhance Sleep Quality and Quantity (COMPLETED) NA NCT07665840 — Effects of L-Theanine and Hericium Erinaceus Gummies on Psychological, Cognitive, and Sleep Quality in University Students (COMPLETED) NA NCT06505694 — A Clinical Trial to Assess the Impact of an Alcohol Alternative Herbal Tincture on Signs of Stress Anxiety and Sleep Quality. (COMPLETED) NA NCT00291070 — Effects of L-Theanine in Boys With ADHD (COMPLETED) PHASE2 NCT07319117 — Evaluation of the Impact of a Nutritional Formulation on Cognitive Performance Following Stress Exposure. (RECRUITING) NA NCT05032729 — Nutritional Intervention to Enhance Sleep Quality and Quantity in Athletes (COMPLETED) NA Published literature Randomized controlled trial Effect of a nutraceutical combination on sleep quality among people with impaired sleep: a randomised, placebo-controlled trial (Scientific reports, 2024) Randomized controlled trial L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial (Journal of psychiatric research, 2019) CT.gov search · Cochrane · PubMed		PubChem
Niacin Natural product Human Study Effect of vitamin E supplementation on chronic insomnia disorder in pos… Human Study Low serum 25-hydroxyvitamin D concentrations in chronic insomnia patien… Human Study This pilot study suggests that the combination of melatonin, vitamin B6…	Nutraceutical	Phase II	Emerging	7	2 trials View evidence Registry trials NCT06971224 — NADream: Effects of Nicotinamide Adenine Dinucleotide Supplementation on Sleep Quality in Healthy Individuals (RECRUITING) PHASE2 NCT05500170 — Benefits of Nicotinamide Riboside Upon Cognition and Sleep (RECRUITING) NA CT.gov search · Cochrane · PubMed		PubChem
Astragalus Natural product Human Study Yiqi Huoxue formula attenuates pressure overload-induced chronic heart…	TCM herb	Preclinical	Emerging	7	—		—
Ginseng Natural product Human Study Yiqi Huoxue formula attenuates pressure overload-induced chronic heart…	Botanical	Preclinical	Emerging	7	—		—
Turmeric Natural product Animal Study A novel potent sleep-promoting effect of turmeric. Animal Study Curcuminoids, a major turmeric component, have a sleep-enhancing effect… Animal Study Nitric oxide modulation is involved in the protective effect of curcumi…	Botanical	Preclinical	Emerging	7	—		PubChem
Schisandra Natural product Animal Study Schisandra possesses potent sedative and hypnotic activity, which suppo…	TCM herb	Preclinical	Emerging	7	—		—
Moringa Natural product Integrated Approach Reveals Fermented Moringa oleifera Leaves Extracts'… Aromatherapy was used to explore the sedative and hypnotic effects of M… Moringa oleifera seed ethanol extract and its active component kaempfer…	Botanical	Preclinical	Emerging	7	—		—
Berberine Natural product Effect of a food supplement containing berberine, monacolin K, hydroxyt…	Botanical	Preclinical	Emerging	7	—		PubChem
Cannabidiol Natural product Human Study Cannabidiol for moderate-severe insomnia Human: Case Report Cannabidiol oil could be used as a safe treatment for reducing anxiety… Animal Study Cannabidiol exerts sedative and hypnotic effects in normal and insomnia…	Food compound	Preclinical	Emerging	2	—		PubChem
Kava Natural product Human Study Kava and valerian root are effective in the treatment of stress-induced… Animal Study Kava kava improves sleep quality in sleep-disturbed rats.	Botanical	Preclinical	Emerging	2	—		—
Terazosin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Yohimbine Natural product Herbal medications for common ailments in the elderly	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Indoramin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Phentolamine Natural product The antidiarrhoeal activity of the aqueous root extract of Aristolochia… Effects of clonidine withdrawal: possible mechanisms and suggestions fo…	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Prazosin Natural product Psychotherapeutic, pharmacological and other active interventions from… Factors impacting prazosin efficacy for nightmares and insomnia in PTSD… Psychotherapeutic and pharmacological agents for post-traumatic stress…	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Tamsulosin Natural product Effects of Prazosin and Other Alpha-1 Adrenergic Antagonist Drugs on Ni… A randomized placebo-controlled study: Phellodendron Bawei tablets comb… Efficacy of combination therapy with tamsulosin and zolpidem on nocturi…	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Clonidine Natural product Efficacy of clonidine and melatonin for treating insomnia in anxious ch… Identifying insomnia-related chemicals through integrative analysis of… Pharmacological treatment for attention deficit hyperactivity disorder…	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Apraclonidine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Doxazosin Natural product Effects of Prazosin and Other Alpha-1 Adrenergic Antagonist Drugs on Ni… [Pharmacological treatment of posttraumatic stress disorder] Novel non-stimulants rescue hyperactive phenotype in an adgrl3.1 mutant…	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Mianserin Natural product Antidepressants for insomnia in adults Antidepressants and their effect on sleep Complaints of poststroke insomnia and its treatment with mianserin	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Akuammigine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Rauwolscine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Corynantheine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Oxymetazoline Natural product Aromatic L-Amino Acid Decarboxylase Deficiency Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors Mechanism of decongestant activity of alpha 2-adrenoceptor agonists	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Nifedipine Natural product Aims of combination therapy--improved quality of life or better blood p…	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Nitrendipine Natural product Comparison of quality of life on nitrendipine and propranolol	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Atipamezole Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Vancomycin Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Desglymidodrine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Phenylpropanolamine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Dexniguldipine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Niguldipine Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
Verapamil Natural product	Food compound	Preclinical	Emerging	0	—	ChEMBL	ChEMBL PubChem ChEMBL
(7-chloro-4-hydroxy-5-phenyl-3H-1,4-benzodiazepin-2-ylidene)-methyl-amine Natural product Human Study Low serum 25-hydroxyvitamin D concentrations in chronic insomnia patien… Human Study Moxibustion is as effective as the benzodiazepine derivative Estrazolam… Animal Study "Valeriana wallichii root extract improves sleep quality and modul…	Food compound	Preclinical	Emerging	0	—	ClinicalTrials.gov	PubChem
Thiamin Natural product	Food compound	Preclinical	Emerging	0	—	ClinicalTrials.gov	PubChem
Cannabis Natural product Human Study Cannabis-based medicine is effective in reducing pain and sleep disturb… Human Study Cannabis may improve pain, mood and sleep in some patients with chronic… Human Study Consumption of medical Cannabis flower is associated with significant i…	Nutraceutical	Preclinical	Emerging	0	—		—
Tart Cherry Natural product Human In Vitro, Human Study Cherry juice increased sleep time and sleep efficiency. Human Study Tart cherry juice may help older adults with insomnia. Human Study The consumption of a tart cherry juice concentrate provides an increase…	Nutraceutical	Preclinical	Emerging	0	—		—
Lactobacillus Plantarum Natural product Human Study Daily consumption of Lactobacillus plantarum PS128 as a dietary supplem… Human Study L. plantarum JYLP-326 could be an effective strategy to alleviate anxie… Human Study Psychobiotic supplementation of PS128 TM improves stress, anxiety, and…	Nutraceutical	Preclinical	Emerging	0	—		—
Flavonoids Natural product Animal Study Neuroprotective effect of Kurarinone against corticosterone-induced cyt… Animal Study Sedative and hypnotic effects of icariin through the GABAergic system p…	Nutraceutical	Preclinical	Emerging	0	—		—
Perilla Natural product Animal Study Sedative and hypnotic effects of Perilla frutescens essential oil throu… Animal Study Sedative effects of inhaled Perilla frutescens essential oils.	Nutraceutical	Preclinical	Emerging	0	—		—
Ziziphus Spinosa Natural product	Nutraceutical	Preclinical	Emerging	0	—		—
Hops Natural product Human Study A combination of valerian and hops reduces sleep latency in patients su…	Nutraceutical	Preclinical	Emerging	0	—		—
Marijuana Natural product Human Study Cannabis may improve pain, mood and sleep in some patients with chronic…	Nutraceutical	Preclinical	Emerging	0	—		—
Cannabinoids Natural product Human Study Cannabis-based medicine is effective in reducing pain and sleep disturb…	Nutraceutical	Preclinical	Emerging	0	—		—
Ayurvedic Formulations Natural product Human Study Comparative impact of yoga and ayurveda practice in insomnia.	Nutraceutical	Preclinical	Emerging	0	—		—
Lettuce Natural product Human Study Lettuce seed decreased insomnia during pregnancy and could be recommend…	Nutraceutical	Preclinical	Emerging	0	—		—
Homeopathic Medicine: All Natural product Human Study Cannabis-based medicine is effective in reducing pain and sleep disturb… Human Study Homeopathic treatment appears to have therapeutic effects in the treatm… Human Study Neurexan might be an effective and well-tolerated alternative to conven…	Nutraceutical	Preclinical	Emerging	0	—		—
Lemon Verbena Natural product Human Study Oral intake of A. citriodora can be suggested as a complementary treatm…	Nutraceutical	Preclinical	Emerging	0	—		—
Basil Natural product Human Study The effect of oral capsule of Ocimum basilicum leaf extract on sleep qu…	Nutraceutical	Preclinical	Emerging	0	—		—
Poppy Natural product Human Study This pilot study suggests that the combination of melatonin, vitamin B6…	Nutraceutical	Preclinical	Emerging	0	—		—
Gourd Natural product Human Study Tryptophan-rich gourd seeds significantly improve subjective and object…	Nutraceutical	Preclinical	Emerging	0	—		—
Pumpkin Seed Oil/Meal Natural product Human Study Tryptophan-rich gourd seeds significantly improve subjective and object…	Nutraceutical	Preclinical	Emerging	0	—		—
Angelica Natural product Human Study Yiqi Huoxue formula attenuates pressure overload-induced chronic heart…	Nutraceutical	Preclinical	Emerging	0	—		—
Persimmon Natural product Animal Study, In Vitro Study The modulatory effects of persimmon leaf extract on sleep-related neuro…	Nutraceutical	Preclinical	Emerging	0	—		—
Fos (Fructooligosaccharides) Natural product Animal Study A non-pharmacological intervention for insomnia: tryptophan-fructooligo…	Nutraceutical	Preclinical	Emerging	0	—		—
Aloe Vera Natural product Animal Study Aloe vera extract has sedative-hypnotic effects in animals.	Nutraceutical	Preclinical	Emerging	0	—		—
Bifidobacterium Animalis Natural product Animal Study Bifidobacterium animalis subsp. lactis Bbm-19 ameliorates insomnia.	Nutraceutical	Preclinical	Emerging	0	—		—
Carotenoids Natural product Animal Study Crocin and crocetin significantly increased the total time of non-rapid…	Nutraceutical	Preclinical	Emerging	0	—		—
Curcuminoids Natural product Animal Study Curcuminoids, a major turmeric component, have a sleep-enhancing effect… Animal Study Nitric oxide modulation is involved in the protective effect of curcumi…	Nutraceutical	Preclinical	Emerging	0	—		—
Lactobacillus Brevis Natural product Human Study Daily consumption of Lactobacillus plantarum PS128 as a dietary supplem… Human Study L. plantarum JYLP-326 could be an effective strategy to alleviate anxie… Human Study Psychobiotic supplementation of PS128 TM improves stress, anxiety, and…	Nutraceutical	Preclinical	Emerging	0	—		—
Hydrogen Water Natural product Animal Study Hydrogen-rich water improves sleep consolidation and enhances forebrain…	Nutraceutical	Preclinical	Emerging	0	—		—
Dogwood Natural product Animal Study Loganin exerts sedative and hypnotic effects.	Nutraceutical	Preclinical	Emerging	0	—		—

Alterations and therapeutics are aggregated from public databases (Open Targets, HPO, ChEMBL, DGIdb, and others). Natural agents are candidates from OSMF narrative reviews on opensourcemed.info/chronic-disease.html — not approved treatments. This page is for research orientation only — not medical advice.