List of investigational social anxiety disorder drugs

This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by adding missing items with reliable sources.

This is a list of investigational social anxiety disorder drugs, or drugs that are currently under development for clinical use in the treatment of social anxiety disorder (SAD; or social phobia) but are not yet approved.

Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.

This list was last comprehensively updated in August 2024. It is likely to become outdated with time.

Under development

Phase 3

• BNC-210 (IW-2143) – α₇-nicotinic acetylcholine receptor negative allosteric modulator ^{[1] [2] [3]}
• Fasedienol (Aloradine; AM-005; PH-94B; 4-androstadienol) – vomeropherine ^{[4] [5]}

Phase 2/3

• Riluzole sublingual (BHV-0223; Nurtec) – complex mechanism of action or glutamatergic modulator ^{[6] [7]}

Phase 2

• Cannabidiol (CBD; ATL5; RLS103) – cannabinoid receptor modulator and other actions ^{[8] [9] [10] [11] [12]}
• FKW00GA (FKW-00GA; TGW-00AA; TGW00AA) – serotonin 5-HT_1A receptor partial agonist and serotonin 5-HT_2A receptor antagonist ^{[13] [7]}
• JNJ-42165279 (JNJ-5279) – fatty acid amide hydrolase (FAAH) inhibitor ^{[14] [15] [11] [16] [17]}
• Oxytocin (intranasal potentiated oxytocin; TI-001; TI-114; TNX-1900; TNX-2900) – oxytocin receptor agonist ^[18]
• Vilazodone (Viibryd) – serotonin 5-HT_1A receptor partial agonist and serotonin reuptake inhibitor ^[19]

Phase 1

• (R)-Midomafetamine ((R)-MDMA; R-MDMA; EMP-01) – serotonin, norepinephrine, and dopamine releasing agent, weak serotonin 5-HT_2A, 5-HT_2B, 5-HT_2C receptor agonist, entactogen, and weak psychedelic hallucinogen ^{[20] [21]}

Preclinical

• Dimethyltryptamine (DMT; N,N-Dimethyltryptamine; N,N-DMT) – non-selective serotonin receptor agonist and psychedelic hallucinogen ^[22]
• PSYLO-3001 (Psylo-3001) – non-selective serotonin receptor agonist and psychedelic hallucinogen ^[23]

Phase unknown

• Fluvoxamine extended-release – selective serotonin reuptake inhibitor ^[24]
• Venlafaxine controlled-release – serotonin–norepinephrine reuptake inhibitor ^[25]

Not under development

No development reported

• Bupropion (Wellbutrin) – norepinephrine–dopamine reuptake inhibitor and nicotinic acetylcholine receptor negative allosteric modulator ^[26]
• EX-597 (KDS-4103; ORG-231295; URB-597) – fatty acid amide hydrolase (FAAH) inhibitor ^{[27] [28]} `
• Guanfacine extended-release (Connexyn; Intuniv; Intuniv XR; S-877503; SHP 503; SPD-503) – α₂-adrenergic receptor agonist ^[29]

Development discontinued

• AV-608 (CGP-60829; NK-608; NKP-608C; NKP608) – neurokinin NK₁ receptor antagonist ^[30]
• Tradipitant (LY-686017; VLY-686) – neurokinin NK₁ receptor antagonist ^[31]
• Verucerfont (GSK-561679; NBI-77860) – corticotropin-releasing hormone receptor 1 (CRF₁) antagonist ^[32]

Formal development never or not yet started

• Small-molecule oxytocin receptor agonists (e.g., LIT-001) ^[33]

Clinically used drugs

Approved drugs

Selective serotonin reuptake inhibitors

• Escitalopram (Lexapro; Cipralex) – selective serotonin reuptake inhibitor ^{[34] [35]}
• Fluvoxamine (Depromel; Luvox) – selective serotonin reuptake inhibitor ^[36]
• Paroxetine (Dropax; Serestill; Paxil; Seroxat) – selective serotonin reuptake inhibitor ^{[37] [38] [35]}
• Sertraline (Zoloft; Lustral) – selective serotonin reuptake inhibitor ^{[39] [35]}

Serotonin–norepinephrine reuptake inhibitors

• Venlafaxine (Dobupal; Effexor; Effexor XR; Elafax) – serotonin–norepinephrine reuptake inhibitor ^{[40] [35]}

Monoamine oxidase inhibitors

• Moclobemide (Manerix) – reversible inhibitor of monoamine oxidase A ^{[41] [35]}

Off-label drugs

• Alcohol (over-the-counter self-medication) – GABA_A receptor positive allosteric modulator ^[42]
• Atypical antipsychotics (e.g., olanzapine, quetiapine) – monoamine receptor modulators ^{[43] [44]}
• Benzodiazepines (e.g., alprazolam, chlordiazepoxide, clonazepam, diazepam, lorazepam, oxazepam) – GABA_A receptor positive allosteric modulators ^{[44] [43]}
• Beta blockers (e.g., atenolol, propranolol) – β-adrenergic receptor antagonists ^{[43] [45] [46]}
• Bupropion (Wellbutrin) – norepinephrine–dopamine reuptake inhibitor and nicotinic acetylcholine receptor negative allosteric modulator ^[44]
• Cannabidiol (CBD) – cannabinoid receptor modulator and other actions, found in cannabis ^{[47] [11] [12]}
• Gabapentinoids (e.g., gabapentin, pregabalin) – α₂δ subunit-containing voltage-dependent calcium channel blockers ^{[43] [44]}
• Monoamine oxidase inhibitors (e.g., phenelzine, selegiline, tranylcypromine) ^[44]
• NMDA receptor antagonists (e.g., ketamine) ^[43]
• Other anticonvulsants (besides gabapentinoids) (e.g., topiramate, valproic acid, tiagabine) ^[43]
• Psychostimulants (e.g., amphetamine, methylphenidate) ^{[10] [48] [49]}
• Selective serotonin reuptake inhibitors (non-licensed) (e.g., citalopram, fluoxetine) ^[43]
• Serotonin–norepinephrine reuptake inhibitors (non-licensed) (e.g., desvenlafaxine, duloxetine) ^{[43] [50]}
• Serotonin 5-HT_1A receptor agonists (e.g., buspirone) ^{[43] [44]}
• Tricyclic antidepressants (e.g., clomipramine, imipramine) ^[43]

See also

• List of investigational drugs
• List of investigational anxiolytics
• List of investigational autism and pervasive developmental disorder drugs

References

1. "BNC 210 - AdisInsight". adisinsight.springer.com.
2. Hampsey E, Perkins A, Young AH (April 2023). "BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders". Expert Opin Investig Drugs. 32 (4): 277–282. doi: 10.1080/13543784.2023.2192922 . PMID   36927202.
3. "Bionomics Starts Phase 3 Trial of BNC210 for Social Anxiety". Synapse. 5 August 2024. Retrieved 5 August 2024.
4. "Fasedienol - Pherin Pharmaceuticals/VistaGen Therapeutics - AdisInsight". adisinsight.springer.com.
5. Singewald N, Sartori SB, Reif A, Holmes A (March 2023). "Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder". Neuropharmacology. 226: 109418. doi:10.1016/j.neuropharm.2023.109418. PMC   10372846 . PMID   36623804.
6. "Riluzole sublingual - Biohaven Pharmaceuticals - AdisInsight". adisinsight.springer.com.
7. Sartori SB, Singewald N (December 2019). "Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders". Pharmacol Ther. 204: 107402. doi: 10.1016/j.pharmthera.2019.107402 . PMID   31470029.
8. "Cannabidiol - ANANDA Scientific - AdisInsight". adisinsight.springer.com.
9. "Phase III clinical trial of Cannabidiol - AdisInsight". adisinsight.springer.com.
10. Pelissolo A, Abou Kassm S, Delhay L (December 2019). "Therapeutic strategies for social anxiety disorder: where are we now?". Expert Rev Neurother. 19 (12): 1179–1189. doi:10.1080/14737175.2019.1666713. PMID   31502896.
11. Ahmed M, Boileau I, Le Foll B, Carvalho AF, Kloiber S (2022). "The endocannabinoid system in social anxiety disorder: from pathophysiology to novel therapeutics". Braz J Psychiatry. 44 (1): 81–93. doi:10.1590/1516-4446-2021-1926. PMC   8827369 . PMID   34468550. The role of the ECS specifically in social anxiety is supported by various preclinical findings which demonstrate effects of ECS modulation, via either CB1 receptor activation or FAAH inhibition, on social interaction and social anxiety.113-118 In comparison, clinical studies investigating this system in SAD are considerably limited. A recent clinical trial investigating the therapeutic effects of a FAAH inhibitor in SAD was negative. However, the authors observed a small to modest anxiolytic effect in patients with severe SAD and suggested that, based on the correlation between low trough concentrations of the inhibitor (i.e., the lowest concentration of the drug in the bloodstream) and low plasma AEA, future trials with a higher dose of the inhibitor may be warranted.119 In addition, a recently published double-blind, placebocontrolled experimental study in healthy adults found that administration of the FAAH inhibitor PF-04457845 produced a 10-fold increase in peripheral AEA levels and decreased broad-spectrum fear-related phenotypes.120 Furthermore, a 2021 double-blind, placebo-controlled clinical trial in healthy males employing the FAAH inhibitor JNJ-42165279 found that the drug attenuated activation in the amygdala, anterior cingulate, and bilateral insula during a face emotion processing task – effects which are consistent with those of previously observed anxiolytic agents.121 Moreover, higher levels of plasma AEA were associated with greater attenuation in these brain regions.121
12. Fliegel DK, Lichenstein SD (December 2022). "Systematic literature review of human studies assessing the efficacy of cannabidiol for social anxiety". Psychiatry Res Commun. 2 (4). doi:10.1016/j.psycom.2022.100074. PMC   9983614 . PMID   36875967.
13. "FKW 00GA - AdisInsight". adisinsight.springer.com.
14. "JNJ 42165279 - AdisInsight". adisinsight.springer.com.
15. Maccarrone M, Di Marzo V, Gertsch J, Grether U, Howlett AC, Hua T, Makriyannis A, Piomelli D, Ueda N, van der Stelt M (September 2023). "Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years". Pharmacol Rev. 75 (5): 885–958. doi:10.1124/pharmrev.122.000600. PMC   10441647 . PMID   37164640. For instance, Paulus and coworkers found that JNJ-42165279 (100 mg) dampens amygdala activity during an emotion face-processing task, an effect that is associated positively with plasma AEA concentrations (Paulus et al., 2021). A lower dose of the drug (25 mg) was tested in a multicenter, placebo-controlled phase 2 trial in patients with social anxiety disorder. The study reported statistically detectable signs of efficacy, but the dosage was considered insufficient to fully inhibit FAAH (Schmidt et al., 2021).
16. Schmidt ME, Liebowitz MR, Stein MB, Grunfeld J, Van Hove I, Simmons WK, Van Der Ark P, Palmer JA, Saad ZS, Pemberton DJ, Van Nueten L, Drevets WC (April 2021). "The effects of inhibition of fatty acid amide hydrolase (FAAH) by JNJ-42165279 in social anxiety disorder: a double-blind, randomized, placebo-controlled proof-of-concept study". Neuropsychopharmacology. 46 (5): 1004–1010. doi:10.1038/s41386-020-00888-1. PMC   8115178 . PMID   33070154.
17. Paulus MP, Stein MB, Simmons AN, Risbrough VB, Halter R, Chaplan SR (April 2021). "The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: a randomized clinical trial". Neuropsychopharmacology. 46 (5): 1011–1019. doi:10.1038/s41386-020-00936-w. PMC   8105363 . PMID   33335310.
18. "Oxytocin - Tonix Pharmaceuticals - AdisInsight". adisinsight.springer.com.
19. "Vilazodone - AbbVie - AdisInsight". adisinsight.springer.com.
20. "EMP 01 - AdisInsight". adisinsight.springer.com.
21. "Delving into the Latest Updates on EMP-01 with Synapse". Synapse. 1 November 2024. Retrieved 2 November 2024.
22. "N N dimethyltryptamine - Psilera - AdisInsight". adisinsight.springer.com.
23. "PSYLO 3001 - AdisInsight". adisinsight.springer.com.
24. "Fluvoxamine extended release - Beijing CoSci Med Tech - AdisInsight". adisinsight.springer.com.
25. "Venlafaxine controlled release - Beijing CoSci Med Tech - AdisInsight". adisinsight.springer.com.
26. "Bupropion - Biovail Corporation - AdisInsight". adisinsight.springer.com.
27. "EX 597 - AdisInsight". adisinsight.springer.com.
28. Kwee CM, Leen NA, Van der Kamp RC, Van Lissa CJ, Cath DC, Groenink L, Baas JM (July 2023). "Anxiolytic effects of endocannabinoid enhancing compounds: A systematic review and meta-analysis". Eur Neuropsychopharmacol. 72: 79–94. doi:10.1016/j.euroneuro.2023.04.001. PMID   37094409.
29. "Guanfacine extended release - Takeda - AdisInsight". adisinsight.springer.com.
30. "AV 608 - AdisInsight". adisinsight.springer.com.
31. "Tradipitant - Vanda Pharmaceuticals - AdisInsight". adisinsight.springer.com.
32. "Verucerfont - GlaxoSmithKline - AdisInsight". adisinsight.springer.com.
33. Nashar PE, Whitfield AA, Mikusek J, Reekie TA (2022). "The Current Status of Drug Discovery for the Oxytocin Receptor". Oxytocin. Methods Mol Biol. Vol. 2384. pp. 153–174. doi:10.1007/978-1-0716-1759-5_10. ISBN   978-1-0716-1758-8. PMID   34550574.
34. "Escitalopram - Lundbeck A/S - AdisInsight". adisinsight.springer.com.
35. Ipser JC, Kariuki CM, Stein DJ (February 2008). "Pharmacotherapy for social anxiety disorder: a systematic review". Expert Rev Neurother. 8 (2): 235–257. doi:10.1586/14737175.8.2.235. PMID   18271710. The SNRI venlafaxine has also been shown to be safe, well- tolerated and more effective than placebo in the short-term treatment of generalized SAD. Paroxetine, sertraline and venla- faxine are currently the only US FDA approved medications for treating SAD, with escitalopram and moclobemide also licensed for use in Europe. MAOIs, in the form of phenelzine, and certain benzodiazepines are also effective in SAD, but in view of concerns about ease of administration (e.g., MAOIs require dietary and medication restrictions) and side effects (e.g., benzodiazepines are associated with cognitive adverse events and require slow withdrawal), its seems reasonable to view these as second-line agents.
36. "Fluvoxamine - AdisInsight". adisinsight.springer.com.
37. "Paroxetine - Novo Nordisk - AdisInsight". adisinsight.springer.com.
38. "Paroxetine hydrochloride - Italfarmaco - AdisInsight". adisinsight.springer.com.
39. "Sertraline - Pfizer - AdisInsight". adisinsight.springer.com.
40. "Venlafaxine - Pfizer - AdisInsight". adisinsight.springer.com.
41. Yáñez M, Padín JF, Arranz-Tagarro JA, Camiña M, Laguna R (2012). "History and therapeutic use of MAO-A inhibitors: a historical perspective of MAO-A inhibitors as antidepressant drug". Curr Top Med Chem. 12 (20): 2275–2282. doi:10.2174/156802612805220011. PMID   23231399. Moclobemide, approved in Europe for the treatment of social phobia/social anxiety disorder, and other reversible inhibitors of MAO-A arise as a promising family of drugs for the treatment of these disorders.
42. Carrigan MH, Randall CL (March 2003). "Self-medication in social phobia: a review of the alcohol literature". Addict Behav. 28 (2): 269–284. doi:10.1016/s0306-4603(01)00235-0. PMID   12573678.
43. Caldiroli A, Capuzzi E, Tagliabue I, Ledda L, Clerici M, Buoli M (February 2023). "New frontiers in the pharmacological treatment of social anxiety disorder in adults: an up-to-date comprehensive overview". Expert Opin Pharmacother. 24 (2): 207–219. doi:10.1080/14656566.2022.2159373. PMID   36519357.
44. Muller JE, Koen L, Seedat S, Stein DJ (2005). "Social anxiety disorder : current treatment recommendations". CNS Drugs. 19 (5): 377–391. doi:10.2165/00023210-200519050-00002. PMID   15907150.
45. Brunello N, den Boer JA, Judd LL, Kasper S, Kelsey JE, Lader M, Lecrubier Y, Lepine JP, Lydiard RB, Mendlewicz J, Montgomery SA, Racagni G, Stein MB, Wittchen HU (October 2000). "Social phobia: diagnosis and epidemiology, neurobiology and pharmacology, comorbidity and treatment". J Affect Disord. 60 (1): 61–74. doi:10.1016/s0165-0327(99)00140-8. PMID   10940449.
46. Halaby A, Haddad R, Naja W (2015). "Non-Antidepressant Treatment of Social Anxiety Disorder: A Review". Curr Clin Pharmacol. 10 (2): 126–130. doi:10.2174/15748847113089990059. PMID   23438729.
47. Rosário BD, Lemes JA, de Lima MP, Ribeiro DA, Viana MB (February 2024). "Subjective, behavioral and neurobiological effects of cannabis and cannabinoids in social anxiety". Rev Neurosci. 35 (2): 197–211. doi:10.1515/revneuro-2023-0078. PMID   37812748.
48. Villas-Boas CB, Chierrito D, Fernandez-Llimos F, Tonin FS, Sanches AC (March 2019). "Pharmacological treatment of attention-deficit hyperactivity disorder comorbid with an anxiety disorder: a systematic review". Int Clin Psychopharmacol. 34 (2): 57–64. doi:10.1097/YIC.0000000000000243. PMID   30422834. In a retrospective analysis of a case series, the monotherapy with extended-release methylphenidate was seen to be effective in reducing ADHD and social AD symptoms evaluated by the Adult ADHD Self-Report Scale (ASRS) and Liebowitz Social Anxiety Scale (LSAS) (Koyuncu et al., 2017).
49. Koyuncu A, İnce E, Ertekin E, Tükel R (2019). "Comorbidity in social anxiety disorder: diagnostic and therapeutic challenges". Drugs Context. 8: 212573. doi:10.7573/dic.212573. PMC   6448478 . PMID   30988687. Attention-deficit/hyperactivity disorder (ADHD), another childhood disorder that extends over adulthood, is an overlooked condition that has high rates of comorbidity with SAD.31 Only recently increasing evidence suggests that the relationship between the two disorders is closer than that was thought before. Several studies found high rates (up to 60–70%) of childhood ADHD comorbidity, especially predominantly inattentive type, in adults with SAD.67,157,158 In addition, follow-up studies showed that the lifetime prevalence of SAD among ADHD patients is higher compared to healthy controls.159 In treatment studies investigating patients with SAD plus ADHD comorbidity found that ADHD medications such as methylphenidate or atomoxetine could effectively improve symptoms of both disorders at the same time.160–163 According to a developmental hypothesis, SAD may be etiologically linked to ADHD in a subgroup of patients, and thus SAD may develop secondary to ADHD.31
50. Mitsui N, Fujii Y, Asakura S, Imai H, Yamada H, Yoshinaga N, Kanai Y, Inoue T, Shimizu E (December 2022). "Antidepressants for social anxiety disorder: A systematic review and meta-analysis". Neuropsychopharmacol Rep. 42 (4): 398–409. doi:10.1002/npr2.12275. PMC   9773641 . PMID   35848723.

Further reading

• Brady LS, Lisanby SH, Gordon JA (2023). "New directions in psychiatric drug development: promising therapeutics in the pipeline". Expert Opin Drug Discov. 18 (8): 835–850. doi:10.1080/17460441.2023.2224555. PMID   37352473.
• PhRMA. "2023 Medicines in Development – Mental Illness" (PDF). PhRMA. Retrieved 5 August 2024.

External links

• AdisInsight - Springer