List of investigational generalized anxiety disorder drugs

Phase 3

• Gepirone (Ariza; BMY-13805; Exxua; Gepirone ER; MJ-13805; Org-33062; TGFK-07AD; TGFK07AD; Travivo; Variza) – serotonin 5-HT_1A receptor partial agonist
• Lysergic acid diethylamide (LSD; lysergide; MM-120; MM120) – non-selective serotonin receptor agonist and psychedelic hallucinogen ^[1]
• Toludesvenlafaxine extended release (4-methylbenzoate desvenlafaxine; ansofaxine; desvenlafaxine prodrug; LPM-570065; LY-03005; Ruoxinlin) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI)
• Vilazodone (EMD-68843; SB-659746A; Viibryd) – serotonin reuptake inhibitor (SRI) and serotonin 5-HT_1A receptor partial agonist

Phase 2/3

• Ulotaront (SEP-363856; SEP-856) – trace amine-associated receptor 1 (TAAR1) agonist and serotonin 5-HT_1A receptor partial agonist

Phase 2

• Desmethylcariprazine prodrug (ABBV-932; RGH-932) – dopamine D₂ and D₃ receptor partial agonist and other actions
• FKW-00GA (FKW00GA; TGW-00AA; TGW00AA) – serotonin 5-HT_1A receptor partial agonist and serotonin 5-HT_2A receptor antagonist
• Lumateperone deuterated (ITI-1284) – atypical antipsychotic (non-selective monoamine receptor modulator
• ONO-1110 – endocannabinoid synthesis regulator and indirect cannabinoid receptor modulator
• TGFK-08AA (TGFK08AA) – serotonin 5-HT_1A receptor modulator
• Vortioxetine (Brintellix; Lu-AA21004; Trintellix; Vortidif) – serotonin reuptake inhibitor, serotonin 5-HT_1A and 5-HT_1B receptor agonist, and serotonin 5-HT_1D, 5-HT₃, and 5-HT₇ receptor antagonist

Phase 1/2

• Non-racemic MDMA (AM-1002; 90% (R)-MDMA, 10% (S)-MDMA) – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT_2A, 5-HT_2B, 5-HT_2C receptor agonist, entactogen, and weak psychedelic hallucinogen ^[2][3]
• PT-00114 (PT100114; TCAP-1) – corticotropin-releasing hormone inhibitor

Phase 1

• NTX-1955 (RO-7308480) – γ₁ subunit-containing GABA_A receptor positive allosteric modulator^[4][5]
• SPT-320 (LYT-320) – agomelatine prodrug (melatonin receptor agonist and weak serotonin 5-HT_2B and 5-HT_2C receptor antagonist)^[6][7]

Preclinical

• Duloxetine oral liquid – serotonin–norepinephrine reuptake inhibitor (SNRI)
• Generalised anxiety disorder therapeutic - SIMR Biotech – undefined mechanism of action
• OV-4041 – potassium–chloride cotransporter agonist
• XYL-3001 (PSYLO-3001) – serotonin 5-HT_2A receptor agonist and non-hallucinogenic psychoplastogen

Phase unknown

• Oxybutynin controlled release – non-selective muscarinic acetylcholine receptor antagonist

Preregistration submission withdrawal

• Quetiapine (FK-949; FK949; ICI-204636; Seroquel; Seroquel XL; Seroquel XR) – atypical antipsychotic (non-selective monoamine receptor modulator)

Suspended

• Agomelatine (AGO-178; AGO178; Alodil; Melitor; S-20098; Thymanax; Valdoxan; Vestin) – melatonin MT₁ and MT₂ receptor agonist and weak serotonin 5-HT_2C receptor antagonist

No development reported

• Guanfacine extended release (Connexyn; Intuniv; Intuniv XR; S-877503; SHP-503; SPD-503) – α₂-adrenergic receptor agonist
• Riluzole sublingual (BHV-0223; Nurtec) – various actions
• Sertraline (Aremis; Besitran; CP-51974; Gladem; Lustral; Serad; Serlain; Tatig; Zoloft) – selective serotonin reuptake inhibitor (SSRI)

Discontinued

• Amibegron (SR-58611; SR-58611A) – β₃-adrenergic receptor agonist
• BTG-1640 (ABIO-08/01; ABIO-0801) – undefined mechanism of action
• Darigabat (CVL-865; PF-06372865; PF-6372865) – GABA_A receptor positive allosteric modulator
• Imagabalin (PD-0332334; PD-332334; PF-00195889) – α₂δ subunit-containing voltage-gated calcium channel ligand
• Naluzotan (PRX-00023) – serotonin 5-HT_1A receptor agonist and sigma σ₁ receptor agonist
• Ocinaplon (CL-273547) – GABA_A receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine
• Pagoclone (IP-456; Panex; RP-62955) – GABA_A receptor positive allosteric modulator and nonbenzodiazepine/cyclopyrrolone
• PF-572778 – undefined mechanism of action
• Rufinamide (Banzel; CGP-33101; E-2080; Inovelon; RUF-331; SYN-111) – sodium channel blocker and other actions
• Talaglumetad (LY-544344) – metabotropic glutamate mGlu₂ and mGlu₃ receptor agonist (eglumetad prodrug)
• Tedatioxetine (Lu-AA24530) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), serotonin 5-HT_2A, 5-HT_2C, and 5-HT₃ receptor antagonist, and α_1A-adrenergic receptor antagonist

Approved drugs

Off-label drugs

• α₂-Adrenergic receptor agonists (e.g., guanfacine)^[8]
• Atypical antipsychotics (non-selective monoamine receptor modulators) (e.g., aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone)^[8]
• Benzodiazepines (GABA_A receptor positive allosteric modulators) (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)^[8][9]
• Beta blockers (β-adrenergic receptor antagonists) (e.g., propranolol)^[10]
• Gabapentinoids (α₂δ subunit-containing voltage-gated calcium channel ligands) (e.g., gabapentin, gabapentin enacarbil)^[9]
• GABA reuptake inhibitors (e.g., tiagabine)^[8][9]
• Monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine)^[8]
• NMDA receptor antagonists (e.g., esketamine, ketamine)^[9]
• Nonbenzodiazepines/Z-drugs (GABA_A receptor positive allosteric modulators) (e.g., eszopiclone)^[8]
• Selective serotonin reuptake inhibitors (SSRIs) (e.g., citalopram, fluoxetine, fluvoxamine, sertraline)^[8]
• Serotonin antagonists and reuptake inhibitors (SARIs) (e.g., trazodone, nefazodone)^[8][11]
• Serotonin modulators and stimulators (SMSs) (e.g., vilazodone, vortioxetine)^[8]
• Tetracyclic antidepressants (TeCAs) (e.g., mirtazapine)^[8]
• Tricyclic antidepressants (TCAs) (e.g., amitriptyline, clomipramine, doxepin, imipramine)^[8]
• Others (e.g., agomelatine, bupropion, hydroxyzine)^[9][12]