List of investigational generalized anxiety disorder drugs
This is a list of investigational generalized anxiety disorder drugs, or drugs that are currently under development for clinical use in the treatment of generalized anxiety disorder (GAD) but are not yet approved.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action [Reference]".
This list was last comprehensively updated in September 2025. It is likely to become outdated with time.
Under development
Phase 3
- Gepirone (Ariza; BMY-13805; Exxua; Gepirone ER; MJ-13805; Org-33062; TGFK-07AD; TGFK07AD; Travivo; Variza) – serotonin 5-HT1A receptor partial agonist [1]
- Lysergic acid diethylamide (LSD; lysergide; MM-120; MM120) – non-selective serotonin receptor agonist and psychedelic hallucinogen [2] [3] [1]
- Toludesvenlafaxine extended release (4-methylbenzoate desvenlafaxine; ansofaxine; desvenlafaxine prodrug; LPM-570065; LY-03005; Ruoxinlin) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) [4]
- Vilazodone (EMD-68843; SB-659746A; Viibryd) – serotonin reuptake inhibitor (SRI) and serotonin 5-HT1A receptor partial agonist [5]
Phase 2/3
- Ulotaront (SEP-363856; SEP-856) – trace amine-associated receptor 1 (TAAR1) agonist and serotonin 5-HT1A receptor partial agonist [6]
Phase 2
- Desmethylcariprazine prodrug (ABBV-932; RGH-932) – dopamine D2 and D3 receptor partial agonist and other actions [7]
- FKW-00GA (FKW00GA; TGW-00AA; TGW00AA) – serotonin 5-HT1A receptor partial agonist and serotonin 5-HT2A receptor antagonist [8]
- Lumateperone deuterated (ITI-1284) – atypical antipsychotic (non-selective monoamine receptor modulator [9]
- ONO-1110 – endocannabinoid synthesis regulator and indirect cannabinoid receptor modulator [10] [11] [12]
- TGFK-08AA (TGFK08AA) – serotonin 5-HT1A receptor modulator [13]
- Vortioxetine (Brintellix; Lu-AA21004; Trintellix; Vortidif) – serotonin reuptake inhibitor, serotonin 5-HT1A and 5-HT1B receptor agonist, and serotonin 5-HT1D, 5-HT3, and 5-HT7 receptor antagonist [14]
Phase 1/2
Phase 1
- SPT-320 (LYT-320) – agomelatine prodrug (melatonin receptor agonist and weak serotonin 5-HT2B and 5-HT2C receptor antagonist)[2][3]
Preclinical
- Duloxetine oral liquid – serotonin–norepinephrine reuptake inhibitor (SNRI) [16]
- Generalised anxiety disorder therapeutic - SIMR Biotech – undefined mechanism of action [17]
- OV-4041 – potassium–chloride cotransporter agonist [18]
- XYL-3001 (PSYLO-3001) – serotonin 5-HT2A receptor agonist and non-hallucinogenic psychoplastogen [19]
Phase unknown
- Oxybutynin controlled release – non-selective muscarinic acetylcholine receptor antagonist [20]
Not under development
Preregistration submission withdrawal
- Quetiapine (FK-949; FK949; ICI-204636; Seroquel; Seroquel XL; Seroquel XR) – atypical antipsychotic (non-selective monoamine receptor modulator) [21]
Suspended
- Agomelatine (AGO-178; AGO178; Alodil; Melitor; S-20098; Thymanax; Valdoxan; Vestin) – melatonin MT1 and MT2 receptor agonist and weak serotonin 5-HT2C receptor antagonist [22]
No development reported
- Guanfacine extended release (Connexyn; Intuniv; Intuniv XR; S-877503; SHP-503; SPD-503) – α2-adrenergic receptor agonist [23]
- Riluzole sublingual (BHV-0223; Nurtec) – various actions [24]
- Sertraline (Aremis; Besitran; CP-51974; Gladem; Lustral; Serad; Serlain; Tatig; Zoloft) – selective serotonin reuptake inhibitor (SSRI) [25]
Discontinued
- Amibegron (SR-58611; SR-58611A) – β3-adrenergic receptor agonist [26]
- BTG-1640 (ABIO-08/01; ABIO-0801) – undefined mechanism of action [27]
- Darigabat (CVL-865; PF-06372865; PF-6372865) – GABAA receptor positive allosteric modulator [28]
- Imagabalin (PD-0332334; PD-332334; PF-00195889) – α2δ subunit-containing voltage-gated calcium channel ligand [29]
- Naluzotan (PRX-00023) – serotonin 5-HT1A receptor agonist and sigma σ1 receptor agonist [30]
- Ocinaplon (CL-273547) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine [31]
- Pagoclone (IP-456; Panex; RP-62955) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/cyclopyrrolone [32]
- PF-572778 – undefined mechanism of action [33]
- Rufinamide (Banzel; CGP-33101; E-2080; Inovelon; RUF-331; SYN-111) – sodium channel blocker and other actions [34]
- Talaglumetad (LY-544344) – metabotropic glutamate mGlu2 and mGlu3 receptor agonist (eglumetad prodrug) [35]
- Tedatioxetine (Lu-AA24530) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), serotonin 5-HT2A, 5-HT2C, and 5-HT3 receptor antagonist, and α1A-adrenergic receptor antagonist [36]
Clinically used drugs
Approved drugs
Selective serotonin reuptake inhibitors (SSRIs)
- Escitalopram (Cipralex; Entact; Lexapro; LU-26054; MLD-55; (S)-citalopram; Seroplex; Sipralex; Sipralexa) – selective serotonin reuptake inhibitor (SSRI) [37]
- Paroxetine (Aropax; BRL-29060; Deroxat; Divarius; FG-7051; Frosinor; Motivan; NNC-207051; Paxil; Seroxat; SI-211103; Tagonis) – selective serotonin reuptake inhibitor (SSRI) [38]
- Paroxetine (Dropax; Dropaxin; Serestill) – selective serotonin reuptake inhibitor (SSRI) [39]
Serotonin–norepinephrine reuptake inhibitors (SNRIs)
- Duloxetine (Ariclaim; Cymbalta; LY-227942; LY-248686; Xeristar; Yentreve) – serotonin–norepinephrine reuptake inhibitor (SNRI) [40]
- Venlafaxine (Dobupal; Efexor XR; Effexor; Effexor XR; Elafax; WY-45030; WY-45651; WY-45655) – serotonin–norepinephrine reuptake inhibitor (SNRI) [41]
Azapirones (serotonin 5-HT1A receptor agonists)
- Buspirone (Buspar) – serotonin 5-HT1A receptor partial agonist and other actions[4]
- Tandospirone (metanopirone; Sediel; SM-3997) – serotonin 5-HT1A receptor partial agonist [42]
GABAA receptor positive allosteric modulators
- Alpidem (Ananxyl; SL800342; SL-800342) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/imidazopyridine [43]
- Alprazolam (Xanax) – GABAA receptor positive allosteric modulator and benzodiazepine
Other drugs
- Opipramol (Ensidon; G-33040; Insidon; Nisidana) – tricyclic antidepressant (TCA) (non-selective monoamine receptor modulator and other actions) [44]
- Pregabalin (CI-1008; isobutylgaba; Lyrica; PD-144723) – gabapentinoid (α2δ subunit-containing voltage-gated calcium channel ligand) [45]
Off-label drugs
- α2-Adrenergic receptor agonists (e.g., guanfacine)[4]
- Atypical antipsychotics (non-selective monoamine receptor modulators) (e.g., aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone)[4]
- Benzodiazepines (GABAA receptor positive allosteric modulators) (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)[4][5]
- Beta blockers (β-adrenergic receptor antagonists) (e.g., propranolol)[6]
- Gabapentinoids (α2δ subunit-containing voltage-gated calcium channel ligands) (e.g., gabapentin, gabapentin enacarbil)[5]
- GABA reuptake inhibitors (e.g., tiagabine)[4][5]
- Monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine)[4]
- NMDA receptor antagonists (e.g., esketamine, ketamine)[5]
- Nonbenzodiazepines/Z-drugs (GABAA receptor positive allosteric modulators) (e.g., eszopiclone)[4]
- Selective serotonin reuptake inhibitors (SSRIs) (e.g., citalopram, fluoxetine, fluvoxamine, sertraline)[4]
- Serotonin antagonists and reuptake inhibitors (SARIs) (e.g., trazodone, nefazodone)[4][7]
- Serotonin modulators and stimulators (SMSs) (e.g., vilazodone, vortioxetine)[4]
- Tetracyclic antidepressants (TeCAs) (e.g., mirtazapine)[4]
- Tricyclic antidepressants (TCAs) (e.g., amitriptyline, clomipramine, doxepin, imipramine)[4]
- Others (e.g., agomelatine, bupropion, hydroxyzine)[5][8]
See also
- Lists of investigational drugs
- List of investigational anxiety disorder drugs
- List of investigational social anxiety disorder drugs
- List of investigational panic disorder drugs
- List of investigational post-traumatic stress disorder drugs
References
- ^ Robison R, Barrow R, Conant C, Foster E, Freedman JM, Jacobsen PL, Jemison J, Karas SM, Karlin DR, Solomon TM, Halperin Wernli M, Fava M (September 2025). "Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial". JAMA. doi:10.1001/jama.2025.13481. PMID 40906494.
- ^ "SPT-320 - Seaport Therapeutics". AdisInsight. 2 January 2024. Retrieved 14 January 2025.
- ^ "Delving into the Latest Updates on SPT-320 with Synapse". Synapse. 21 November 2024. Retrieved 14 January 2025.
By leveraging Glyph, SPT-320 bypasses liver first-pass metabolism, allowing for lower dosing and reduced liver exposure.
- ^ a b c d e f g h i j k l Strawn JR, Geracioti L, Rajdev N, Clemenza K, Levine A (July 2018). "Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review". Expert Opin Pharmacother. 19 (10): 1057–1070. doi:10.1080/14656566.2018.1491966. PMC 6340395. PMID 30056792.
- ^ a b c d e Fagan HA, Baldwin DS (June 2023). "Pharmacological Treatment of Generalised Anxiety Disorder: Current Practice and Future Directions". Expert Rev Neurother. 23 (6): 535–548. doi:10.1080/14737175.2023.2211767. PMID 37183813.
- ^ Tyrer P, Baldwin D (December 2006). "Generalised anxiety disorder". Lancet. 368 (9553): 2156–2166. doi:10.1016/S0140-6736(06)69865-6. PMID 17174708.
- ^ Davidson JR, Zhang W, Connor KM, Ji J, Jobson K, Lecrubier Y, McFarlane AC, Newport DJ, Nutt DJ, Osser DN, Stein DJ, Stowe ZN, Tajima O, Versiani M (January 2010). "A psychopharmacological treatment algorithm for generalised anxiety disorder (GAD)". J Psychopharmacol. 24 (1): 3–26. doi:10.1177/0269881108096505. PMC 2951594. PMID 18832431.
- ^ Stein DJ (September 2021). "Evidence-Based Pharmacotherapy of Generalised Anxiety Disorder: Focus on Agomelatine". Adv Ther. 38 (Suppl 2): 52–60. doi:10.1007/s12325-021-01860-1. PMC 8437845. PMID 34417992.