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 It is likely to become outdated with time.
^ abPelissolo 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. PMID31502896.
^ abcAhmed 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. PMC8827369. PMID34468550. 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
^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. PMC10441647. PMID37164640. 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).
^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. PMID37094409.
^ abcdeIpser 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. PMID18271710. 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.
^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. PMID23231399. 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.
^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. PMID12573678.
^ abcdefghijCaldiroli 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. PMID36519357.
^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. PMID23438729.
^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. PMID37812748.
^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. PMID30422834. 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).
^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. PMC6448478. PMID30988687. 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
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. PMID37352473.