Biomarker & Intervention Discovery

Fibromyalgia

Pharmacologically actionable gene targets, therapeutic agents ranked by evidence tier, and active clinical trials.

US DALYs4.08MWHO GHE 2021 · all ages
Global DALYs45.69MWHO GHE 2021 · worldwide
US mortality12.5K deaths/yrWHO GHE 2021
Global mortality110.0K deaths/yrWHO GHE 2021 · worldwide
NIH funding$15MFY2025 · RCDC estimate
Funding levelSeverely Underfunded
Spontaneous remissionPartial spontaneous improvement in ~25-30% over 5 years; complete resolution without treatment rare; chronic…
Best-intervention remissionMultimodal approach (aerobic exercise + CBT + sleep optimisation): most effective combination — 50-60% significant…
Gap sizeLarge — pharmacotherapy is modestly effective; exercise is the most effective single intervention but chronically…
Primary barrierframing/practice
Full remission profile →
Research Tracker / Chronic Disease Interventions / Fibromyalgia

Remission & chronicity

Spontaneous remission
Partial spontaneous improvement in ~25-30% over 5 years; complete resolution without treatment rare; chronic fluctuating course in majority; central sensitisation often persists
Best-intervention remission
Multimodal approach (aerobic exercise + CBT + sleep optimisation): most effective combination — 50-60% significant improvement; duloxetine: 50% pain response in 43% vs 29% placebo; milnacipran: similar; pregabalin: 50% pain response 38-50%; low-dose naltrexone (LDN): 30% improvement in open-label studies
Gap size
Large — pharmacotherapy is modestly effective; exercise is the most effective single intervention but chronically underused as 'too painful'; disease is often dismissed
Primary barrier
framing/practice
Fibromyalgia was dismissed as non-organic by mainstream medicine for decades; this has resulted in: delayed diagnosis (mean 5 years), inappropriate investigations, ineffective treatments (opioids in particular), and under-referral to physiotherapy and psychological therapies; the 2010 ACR criteria removed tender point requirement and improved diagnosis
Biomarker Targets & Therapeutic Agents

Gene targets queried against DGIdb, Open Targets, ChEMBL, PubMed, and Europe PMC. Agents ranked: ● Clinical > ● Mechanistic > ● Correlative.

GRIN1 183GRIN2B 238SCN9A 271SLC6A2 269SLC6A4 224TRPV1 160

GRIN1

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
COMPOUND 53 [PMID: 33038794] ↑ activates Mechanistic DGIdb
PAREGORIC ? unclear Mechanistic DGIdb
STING AGONIST 2 ↑ activates Mechanistic DGIdb
LATREPIRDINE ? unclear Mechanistic DGIdb
CNS-5161 ↓ inhibits Mechanistic DGIdb
MEMANTINE HYDROCHLORIDE ~ modulates Mechanistic DGIdb
LANICEMINE ↓ inhibits Mechanistic DGIdb
ULEVOSTINAG ↑ activates Mechanistic DGIdb
ELIPRODIL ? unclear Mechanistic DGIdb
NBQX ? unclear Mechanistic DGIdb
RAPASTINEL ? unclear Mechanistic DGIdb
DEXANABINOL ? unclear Mechanistic DGIdb
NEBOGLAMINE ~ modulates Mechanistic DGIdb
HALOPERIDOL DECANOATE ? unclear Mechanistic DGIdb
ORPHENADRINE ? unclear Mechanistic DGIdb
GW468816 ↓ inhibits Mechanistic DGIdb
ACAMPROSATE CALCIUM ↓ inhibits Mechanistic DGIdb
AMANTADINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
H-151 ↓ inhibits Mechanistic DGIdb
D-SERINE ? unclear Mechanistic DGIdb
AZD8108 ↓ inhibits Mechanistic DGIdb
KETAMINE HYDROCHLORIDE ~ modulates Mechanistic DGIdb
DELUCEMINE ↓ inhibits Mechanistic DGIdb
EVT-101 ↓ inhibits Mechanistic DGIdb
MSA-2 ↑ activates Mechanistic DGIdb
ESKETAMINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
2'3'-CGAMP ↑ activates Mechanistic DGIdb
COMPOUND 40 [PMID: 33470814] ↑ activates Mechanistic DGIdb
PHILANTHOTOXIN 343 ? unclear Mechanistic DGIdb
FELBAMATE ↓ inhibits Mechanistic DGIdb
INDANTADOL ↓ inhibits Mechanistic DGIdb
STING AGONIST 3 ↑ activates Mechanistic DGIdb
ORPHENADRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
CYCLOSERINE ? unclear Mechanistic DGIdb
RADIPRODIL ↓ inhibits Mechanistic DGIdb
PERZINFOTEL ↓ inhibits Mechanistic DGIdb
ESKETAMINE ~ modulates Mechanistic DGIdb
ADU-S100 ↑ activates Mechanistic DGIdb
RALFINAMIDE ↓ inhibits Mechanistic DGIdb
SNX281 ↑ activates Mechanistic DGIdb

Showing top 40 of 183 agents ranked by evidence tier.

GRIN2B

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
DIMIRACETAM ? unclear Mechanistic DGIdb
KETAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
PERZINFOTEL ↓ inhibits Mechanistic DGIdb
[3H]CGP39653 ↓ inhibits Mechanistic DGIdb
PHENCYCLIDINE ↓ inhibits Mechanistic DGIdb
DEXANABINOL ? unclear Mechanistic DGIdb
RAPASTINEL ↑ activates Mechanistic DGIdb
DELUCEMINE ↓ inhibits Mechanistic DGIdb
AMANTADINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
RISLENEMDAZ ↓ inhibits Mechanistic DGIdb
ORPHENADRINE CITRATE ↓ inhibits Mechanistic DGIdb
ELIPRODIL ? unclear Mechanistic 13.0 nM (Ki) DGIdb
INDANTADOL ? unclear Mechanistic DGIdb
SEVOFLURANE ? unclear Mechanistic DGIdb
SAGE-718 ~ modulates Mechanistic DGIdb
L689560 ↓ inhibits Mechanistic DGIdb
ONFASPRODIL ~ modulates Mechanistic DGIdb
HOMOQUINOLINIC ACID ↑ activates Mechanistic DGIdb
NEBOGLAMINE ~ modulates Mechanistic DGIdb
DIZOCILPINE ↓ inhibits Mechanistic DGIdb
LY233053 ↓ inhibits Mechanistic DGIdb
GLYCINE ↑ activates Mechanistic DGIdb
ESKETAMINE ~ modulates Mechanistic DGIdb
[3H]CGP61594 ↓ inhibits Mechanistic DGIdb
ORPHENADRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
[3H]MDL105519 ↓ inhibits Mechanistic DGIdb
RADIPRODIL ? unclear Mechanistic DGIdb
NBQX ? unclear Mechanistic DGIdb
SEMAPIMOD ↓ inhibits Mechanistic DGIdb
SELFOTEL ↓ inhibits Mechanistic DGIdb
SERINE, D- ↑ activates Mechanistic DGIdb
COMPOUND 18C [PMID: 25901531] ↓ inhibits Mechanistic DGIdb
AZD8108 ↓ inhibits Mechanistic DGIdb
[3H]L689560 ↓ inhibits Mechanistic DGIdb
TRAXOPRODIL ↓ inhibits Mechanistic 74.0 nM (IC50) DGIdb
HALOPERIDOL DECANOATE ? unclear Mechanistic DGIdb
N1-DANSYL-SPERMINE ↓ inhibits Mechanistic DGIdb
[3H]D-ASPARTIC ACID ↑ activates Mechanistic DGIdb
NERAMEXANE ? unclear Mechanistic DGIdb
NVP-AAM077 ↓ inhibits Mechanistic DGIdb

Showing top 40 of 238 agents ranked by evidence tier.

SCN9A

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
MERETHOXYLLINE PROCAINE ↓ inhibits Mechanistic DGIdb
ETIDOCAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
FOSPHENYTOIN ↓ inhibits Mechanistic DGIdb
VERATRIDINE ↑ activates Mechanistic DGIdb
ORPHENADRINE CITRATE ↓ inhibits Mechanistic DGIdb
PHENACEMIDE ↓ inhibits Mechanistic DGIdb
LACOSAMIDE ↓ inhibits Mechanistic DGIdb
VIXOTRIGINE ↓ inhibits Mechanistic DGIdb
DSP-2230 ↓ inhibits Mechanistic DGIdb
SAXITOXIN ↓ inhibits Mechanistic DGIdb
ESLICARBAZEPINE ACETATE ↓ inhibits Mechanistic DGIdb
SAFINAMIDE ? unclear Mechanistic DGIdb
LIDOCAINE ↓ inhibits Mechanistic DGIdb
RILUZOLE ↓ inhibits Mechanistic DGIdb
ROPIVACAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
FUNAPIDE ↓ inhibits Mechanistic DGIdb
DYCLONINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
EVENAMIDE ↓ inhibits Mechanistic DGIdb
PROPOFOL ? unclear Mechanistic DGIdb
AM-6120 ↓ inhibits Mechanistic DGIdb
RG7893 ↓ inhibits Mechanistic DGIdb
RG6029 ↓ inhibits Mechanistic DGIdb
QUINIDINE SULFATE ↓ inhibits Mechanistic DGIdb
ZONISAMIDE ↓ inhibits Mechanistic DGIdb
NERISPIRDINE ↓ inhibits Mechanistic DGIdb
RALFINAMIDE ↓ inhibits Mechanistic DGIdb
DS-1971A ↓ inhibits Mechanistic DGIdb
HEXYLCAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
MEPIVACAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
PROCAINAMIDE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
PROPAFENONE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
LIDOCAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
QUINIDINE GLUCONATE ↓ inhibits Mechanistic DGIdb
PRILOCAINE ↓ inhibits Mechanistic DGIdb
ETHOTOIN ↓ inhibits Mechanistic DGIdb
PF-05089771 ↓ inhibits Mechanistic DGIdb
DICHLOROBENZYL ALCOHOL ↓ inhibits Mechanistic DGIdb
RANOLAZINE ? unclear Mechanistic DGIdb
PRILOCAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
ORPHENADRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb

Showing top 40 of 271 agents ranked by evidence tier.

SLC6A2

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
TESOFENSINE ↓ inhibits Mechanistic DGIdb
PHENMETRAZINE ? unclear Mechanistic DGIdb
VENLAFAXINE ? unclear Mechanistic 1060.0 nM (Kd) DGIdb
SIBUTRAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
DEXMETHYLPHENIDATE ↓ inhibits Mechanistic DGIdb
TRIMIPRAMINE ? unclear Mechanistic DGIdb
CLOMIPRAMINE ? unclear Mechanistic DGIdb
GUANADREL SULFATE ? unclear Mechanistic DGIdb
TAPENTADOL HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
LISDEXAMFETAMINE DIMESYLATE ? unclear Mechanistic DGIdb
PROTRIPTYLINE ? unclear Mechanistic DGIdb
DESVENLAFAXINE SUCCINATE ↓ inhibits Mechanistic DGIdb
ATOMOXETINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
IOBENGUANE I-123 ? unclear Mechanistic DGIdb
SURONACRINE MALEATE ? unclear Mechanistic DGIdb
REBOXETINE ↓ inhibits Mechanistic 1.1 nM (Ki) DGIdb
BICIFADINE ↓ inhibits Mechanistic DGIdb
DOXEPIN HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
LIAFENSINE ↓ inhibits Mechanistic DGIdb
ORPHENADRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
DULOXETINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
DASOTRALINE ↓ inhibits Mechanistic DGIdb
DESIPRAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
METHYLPHENIDATE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
AMITIFADINE ↓ inhibits Mechanistic DGIdb
NEFAZODONE ? unclear Mechanistic 360.0 nM (Kd) DGIdb
AMITIFADINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
DEXTROAMPHETAMINE SULFATE ? unclear Mechanistic DGIdb
TYROSINE HYDROXYLASE INHIBITOR ? unclear Mechanistic DGIdb
NORTRIPTYLINE ? unclear Mechanistic 6.3 nM (Ki) DGIdb
MAPROTILINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
ST. JOHN'S WORT ? unclear Mechanistic DGIdb
DEXTROAMPHETAMINE SACCHARATE ? unclear Mechanistic DGIdb
AMOXAPINE ↓ inhibits Mechanistic DGIdb
PHENDIMETRAZINE ↓ inhibits Mechanistic DGIdb
PHENYLPROPANOLAMINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
BUPROPION HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
BETHANIDINE ? unclear Mechanistic DGIdb
TRAMADOL ? unclear Mechanistic DGIdb
MILNACIPRAN ? unclear Mechanistic DGIdb

Showing top 40 of 269 agents ranked by evidence tier.

SLC6A4

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
CENTANAFADINE ↓ inhibits Mechanistic DGIdb
METHAMPHETAMINE ↓ inhibits Mechanistic DGIdb
VENLAFAXINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
LUMATEPERONE ↓ inhibits Mechanistic DGIdb
TIANEPTINE ? unclear Mechanistic DGIdb
IMIPRAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
ONDANSETRON HYDROCHLORIDE ? unclear Mechanistic DGIdb
PEGINTERFERON ALFA-2B ? unclear Mechanistic DGIdb
DEXFENFLURAMINE ? unclear Mechanistic DGIdb
BUPROPION HYDROCHLORIDE ? unclear Mechanistic DGIdb
CITALOPRAM ↓ inhibits Mechanistic 1.6 nM (Ki) DGIdb
TRIMIPRAMINE ? unclear Mechanistic DGIdb
VENLAFAXINE ? unclear Mechanistic 8.9 nM (Kd) DGIdb
DISULFIRAM ? unclear Mechanistic DGIdb
CHLORPHENTERMINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
PROTRIPTYLINE ? unclear Mechanistic DGIdb
MILNACIPRAN HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
CLOMIPRAMINE ? unclear Mechanistic 70.0 nM (IC50) DGIdb
NORTRIPTYLINE ? unclear Mechanistic DGIdb
DAPOXETINE ↓ inhibits Mechanistic DGIdb
AMITRIPTYLINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
TEDATIOXETINE ↓ inhibits Mechanistic DGIdb
TRAZODONE ↓ inhibits Mechanistic DGIdb
SERTRALINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
EVODIAMINE ? unclear Mechanistic DGIdb
PSEUDOEPHEDRINE ? unclear Mechanistic DGIdb
FLUOXETINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
SIBUTRAMINE ? unclear Mechanistic DGIdb
TRAMADOL ? unclear Mechanistic DGIdb
VORTIOXETINE HYDROBROMIDE ↓ inhibits Mechanistic DGIdb
BL-1021 ? unclear Mechanistic DGIdb
DOXEPIN HYDROCHLORIDE ? unclear Mechanistic DGIdb
DOTHIEPIN ↓ inhibits Mechanistic DGIdb
DEXTROMETHORPHAN POLISTIREX ? unclear Mechanistic DGIdb
DESIPRAMINE ? unclear Mechanistic DGIdb
PHENTERMINE RESIN ? unclear Mechanistic DGIdb
NORTRIPTYLINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
MONOAMINE OXIDASE INHIBITOR ? unclear Mechanistic DGIdb
MILNACIPRAN ? unclear Mechanistic DGIdb
RIBAVIRIN ? unclear Mechanistic DGIdb

Showing top 40 of 224 agents ranked by evidence tier.

TRPV1

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
STREPTOZOCIN ? unclear Mechanistic DGIdb
BENZYL ISOTHIOCYANATE ? unclear Mechanistic DGIdb
ACETAMINOPHEN ↑ activates Mechanistic DGIdb
POLYGODIAL ? unclear Mechanistic DGIdb
PROPOFOL ? unclear Mechanistic DGIdb
SAF312 ↓ inhibits Mechanistic DGIdb
GRC-15300 ? unclear Mechanistic DGIdb
AZD1386 ↓ inhibits Mechanistic DGIdb
TIVANISIRAN ↓ inhibits Mechanistic DGIdb
MAVATREP ↓ inhibits Mechanistic DGIdb
MR-1817 ↓ inhibits Mechanistic DGIdb
FERRUGINENE B ? unclear Mechanistic DGIdb
CAPSAICIN ↑ activates Mechanistic 19.95 nM (EC50) DGIdb
RECOMBINANT TUMOR NECROSIS FACTOR FAMILY PROTEIN ? unclear Mechanistic DGIdb
PHENETHYLISOTHIOCYANATE ? unclear Mechanistic DGIdb
VOACANGINE ? unclear Mechanistic DGIdb
RESINIFERATOXIN ↑ activates Mechanistic 23.1 nM (Ki) DGIdb
DWP05195 ↓ inhibits Mechanistic DGIdb
XEN-D0501 ↓ inhibits Mechanistic DGIdb
PAC-14028 ↓ inhibits Mechanistic DGIdb
SB-705498 ↓ inhibits Mechanistic DGIdb
MASOPROCOL ? unclear Mechanistic DGIdb
ALLYL ISOTHIOCYANATE ? unclear Mechanistic DGIdb
NGD-8243 ↓ inhibits Mechanistic DGIdb
GRC-6211 ↓ inhibits Mechanistic DGIdb
RESERPINE ? unclear Mechanistic DGIdb
NABIXIMOLS ? unclear Mechanistic DGIdb
A425619 ? unclear Mechanistic DGIdb
PHE377 ↓ inhibits Mechanistic DGIdb
ANTISENSE OLIGONUCLEOTIDES ? unclear Mechanistic DGIdb
WORTMANNIN ? unclear Mechanistic DGIdb
JTS-653 ↓ inhibits Mechanistic DGIdb
LEVODOPA ? unclear Mechanistic DGIdb
AMG517 ↓ inhibits Mechanistic DGIdb
CAPSAZEPINE ? unclear Mechanistic 120.0 nM (Ki) DGIdb
ZUCAPSAICIN ↑ activates Mechanistic DGIdb
INDOMETHACIN ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL191534 ? unclear Mechanistic DGIdb
ABT-102 ↓ inhibits Mechanistic DGIdb
ISOPROPYL ISOTHIOCYANATE ? unclear Mechanistic DGIdb

Showing top 40 of 160 agents ranked by evidence tier.

Clinical Trials

Recruiting and recently completed trials from ClinicalTrials.gov. Data retrieved 2026-07-06.

No recent clinical trials found on ClinicalTrials.gov for this condition.

Agents Found By Disease-Level Search

Searched directly from “Fibromyalgia” via ClinicalTrials.gov interventions and Open Targets' disease→drug data — independent of the 6-gene target panel above. This surfaces agents whose mechanism doesn't route through a curated gene (combination therapies, standard-of-care drugs, targets outside the panel).

Not yet run. python -m biomarker_pipeline.run_disease_agent_discovery --disease "..."

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