Pharmacological breakthroughs in anxiety management: exploring traditional and emerging therapies

Authors

  • V. Venkata Rajesham CMR College of Pharmacy, Kandlakoya (V), Medchal Road, Hyderabad, Telangana, India
  • Akula Sai Nandini CMR College of Pharmacy, Kandlakoya (V), Medchal Road, Hyderabad, Telangana, India
  • Akula Sai Nandini CMR College of Pharmacy, Kandlakoya (V), Medchal Road, Hyderabad, Telangana, India
  • Arghyarupa Behera CMR College of Pharmacy, Kandlakoya (V), Medchal Road, Hyderabad, Telangana, India
  • T. Rama Rao CMR College of Pharmacy, Kandlakoya (V), Medchal Road, Hyderabad, Telangana, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20253381

Keywords:

Anxiety disorders, Generalized anxiety disorder, Panic disorder, Social anxiety disorder, Specific phobias

Abstract

Anxiety disorders are the most common psychiatric disorders and a significant cause of disability. While there is ongoing research into posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative lack of innovative drugs being investigated for anxiety disorders. The first goal of this review is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD) and specific phobias (SP), which include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), antipsychotics, alpha- and beta-adrenergic medications (e.g., propranolol, clonidine) and GABAergic medications (benzodiazepines). Second, we will look at new pharmacotherapeutic drugs being investigated for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents and natural remedies.

 

 

Metrics

Metrics Loading ...

References

Vos T, Abajobir AA, Abbafati C. Global, regional and national incidence, prevalence and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211–59. DOI: https://doi.org/10.1016/S0140-6736(17)32154-2

Gustavsson A, Svensson M, Jacobi F. Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21(10):718–79. DOI: https://doi.org/10.1016/j.euroneuro.2011.08.008

Alonso J, Liu Z, Evans-Lacko S. Treatment gap for anxiety disorders is global: results of the World Mental Health Surveys in 21 countries. Depress Anxiety. 2018;35(3):195–208. DOI: https://doi.org/10.1002/da.22711

Fagan HA, Baldwin DS. Pharmacological Treatment of Generalised Anxiety Disorder: Current Practice and Future Directions. Expert Rev Neurother. 2023;23(6):535-48. DOI: https://doi.org/10.1080/14737175.2023.2211767

Roy-Byrne PP, Craske MG, Stein MB. Panic disorder. Lancet. 2006;368(9540):1023–32. DOI: https://doi.org/10.1016/S0140-6736(06)69418-X

Miloyan B, Bienvenu OJ, Brilot B, Eaton WW. Adverse life events and the onset of anxiety disorders. Psychiatry Res. 2018;259:488–92. DOI: https://doi.org/10.1016/j.psychres.2017.11.027

Rapp MS, Thomas MR. Agoraphobia: nature, treatments and myths. Lancet. 1982;1(8283):342-345.

Leichsenring F, Leweke F. Social Anxiety Disorder. N Engl J Med. 2017;376(23):2255-64. DOI: https://doi.org/10.1056/NEJMcp1614701

Fountoulakis KN, Karakatsoulis GN, Abraham S. Results of the COVID-19 Mental Health International for the Health Professionals (COMET-HP) Study: Depression, Suicidal Tendencies and Conspiracism. Soc Psychiatry Psychiatr Epidemiol. 2023;58(3):331-45. DOI: https://doi.org/10.1007/s00127-023-02438-8

Schiele MA, Domschke K. Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders. Genes Brain Behav. 2018;17:12423. DOI: https://doi.org/10.1111/gbb.12423

Batelaan NM, Rhebergen D, de Graaf R, Spijker J, Beekman ATF, Penninx BWJH. Panic attacks as a dimension of psychopathology. J Clin Psychiatry. 2012;73(9):1195–202. DOI: https://doi.org/10.4088/JCP.12m07743

Eaton WW, Bienvenu OJ, Miloyan B, Scholten WD, Batelaan NM, Penninx BWJH. Diagnostic instability of recurrence and the impact on recurrence rates in depressive and anxiety disorders. J Affect Disord. 2016;195:185–90. DOI: https://doi.org/10.1016/j.jad.2016.02.025

Hendriks SM, Spijker J, Licht CMM, Beekman ATF, Penninx BWJH. Two-year course of anxiety disorders: different across disorders or dimensions. Acta Psychiatr Scand. 2013;128(3):212–21. DOI: https://doi.org/10.1111/acps.12024

Hendriks SM, Spijker J, Licht CMM. Long-term disability in anxiety disorders. BMC Psychiatry. 2016;16:248. DOI: https://doi.org/10.1186/s12888-016-0946-y

Robins LN, Wing J, Wittchen HU. The composite international diagnostic interview. Arch Gen Psychiatry. 1988;45(12):1069. DOI: https://doi.org/10.1001/archpsyc.1988.01800360017003

Spitzer RL, Williams JBW, Gibbon M, First MB. The structured clinical interview for DSM-III-R (SCID). Arch Gen Psychiatry. 1992;49(8):624. DOI: https://doi.org/10.1001/archpsyc.1992.01820080032005

Ambrosini PJ. Historical development and present status of the schedule for affective disorders and schizophrenia for school-age children (K-SADS). J Am Acad Child Adolesc Psychiatry. 2000;39(1):49–58. DOI: https://doi.org/10.1097/00004583-200001000-00016

Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70. DOI: https://doi.org/10.1111/j.1600-0447.1983.tb09716.x

Song K, Wang Y, Shen L, Wang J, Zhang R. Complementary and alternative therapies for generalized anxiety disorder: A protocol for systematic review and network meta-analysis. Medicine. 2022;101(50):32115. DOI: https://doi.org/10.1097/MD.0000000000032401

Otto MW, Tuby KS, Gould RA. An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder. Am J Psychiatry. 2001;158(12):1989–92. DOI: https://doi.org/10.1176/appi.ajp.158.12.1989

Griebel G, Holmes A. 50 years of hurdles and hope in anxiolytic drug discovery. Nat Rev Drug Discov. 2013;12(9):667–87. DOI: https://doi.org/10.1038/nrd4075

Erickson SR, Guthrie S, Vanetten-Lee M. Severity of anxiety and work-related outcomes of patients with anxiety disorders. Depress Anxiety. 2009;26(12):1165–71. DOI: https://doi.org/10.1002/da.20624

Senaratne R, Van Ameringen M, Mancini C, Patterson B. The burden of anxiety disorders on the family. J Nerv Ment Dis. 2010;198(12):876–80. DOI: https://doi.org/10.1097/NMD.0b013e3181fe7450

Martin-Merino E, Ruigomez A, Wallander MA. Prevalence, incidence, morbidity and treatment patterns in a cohort of patients diagnosed with anxiety in UK primary care. Fam Pract. 2010;27(1):9–16. DOI: https://doi.org/10.1093/fampra/cmp071

Waghorn G, Chant D, White P, Whiteford H. Disability, employment and work performance among people with ICD-10 anxiety disorders. Aust NZJ Psychiatry. 2005;39(2):55–66. DOI: https://doi.org/10.1111/j.1440-1614.2005.01510.x

Watanabe N, Churchill R, Furukawa TA. Combined psychotherapy plus benzodiazepines for panic disorder. Cochrane Database Syst Rev. 2009;(1):5335. DOI: https://doi.org/10.1002/14651858.CD005335.pub2

Imai H, Tajika A, Chen P. Azapirones versus placebo for panic disorder in adults. Cochrane Database Syst Rev. 2014;9:10828. DOI: https://doi.org/10.1002/14651858.CD010828.pub2

Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for posttraumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2006;(1):2795. DOI: https://doi.org/10.1002/14651858.CD002795.pub2

Kapczinski F, Lima MS, Souza JS, Schmitt R. Antidepressants for generalized anxiety disorder. Cochrane Database Syst Rev. 2003;(2):3592. DOI: https://doi.org/10.1002/14651858.CD003592

Institute of Medicine. Treatment of posttraumatic stress disorder: an assessment of the evidence. Washington, D.C: National Academies Press. 2008;3:69.

Murrough JW, Yaqubi S, Sayed S, Charney DS. Emerging drugs for the treatment of anxiety. Expert Opin Emerg Drugs. 2015;20(3):375–87. DOI: https://doi.org/10.1517/14728214.2015.1049996

Cuijpers P, Sijbrandij M, Koole SL. The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: A meta-analysis of direct comparisons. World Psychiatry. 2013;12(2):137–48. DOI: https://doi.org/10.1002/wps.20038

Bang-Andersen B, Ruhland T, Jorgensen M. Discovery of 1-(2-(2,4-dimethylphenylsulfanyl) phenyl) piperazine (Lu AA21004): A novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011;54(9):3206–21. DOI: https://doi.org/10.1021/jm101459g

Gibb A, Deeks ED. Vortioxetine: First global approval. Drugs. 2014;74(1):135–45. DOI: https://doi.org/10.1007/s40265-013-0161-9

Bidzan L, Mahableshwarkar AR, Jacobsen P. Vortioxetine (Lu AA21004) in generalized anxiety disorder: Results of an 8-week, multinational, randomized, double-blind, placebo-controlled clinical trial. Eur Neuropsychopharmacol. 2012;22(12):847–57. DOI: https://doi.org/10.1016/j.euroneuro.2012.07.012

Rothschild AJ, Mahableshwarkar AR, Jacobsen P. Vortioxetine (Lu AA21004) 5 mg in generalized anxiety disorder: Results of an 8-week randomized, double-blind, placebo-controlled clinical trial in the United States. Eur Neuropsychopharmacol. 2012;22(12):858–66. DOI: https://doi.org/10.1016/j.euroneuro.2012.07.011

Dawson LA. The discovery and development of vilazodone for the treatment of depression: A novel antidepressant or simply another SSRI? Expert Opin Drug Discov. 2013;8(12):1529–39. DOI: https://doi.org/10.1517/17460441.2013.855195

Pierz KA, Thase ME. A review of vilazodone, serotonin and major depressive disorder. Prim Care Companion CNS Disord. 2014;16(1):10.4088/PCC.13r01554. DOI: https://doi.org/10.4088/PCC.13r01554

Thase ME, Chen D, Edwards J, Ruth A. Efficacy of vilazodone on anxiety symptoms in patients with major depressive disorder. Int Clin Psychopharmacol. 2014;29(6):351–6. DOI: https://doi.org/10.1097/YIC.0000000000000045

Clayton AH, Pradko JF, Croft HA. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry. 2002;63(4):357–66. DOI: https://doi.org/10.4088/JCP.v63n0414

Tardito D, Molteni R, Popoli M, Racagni G. Synergistic mechanisms involved in the antidepressant effects of agomelatine. Eur Neuropsychopharmacol. 2012;22(Suppl 3): S482-6. DOI: https://doi.org/10.1016/j.euroneuro.2012.06.016

Soumier A, Banasr M, Lortet S. Mechanisms contributing to the phase dependent regulation of neurogenesis by the novel antidepressant, agomelatine, in the adult rat hippocampus. Neuropsychopharmacology. 2009;34(11):2390-403. DOI: https://doi.org/10.1038/npp.2009.72

Stein DJ, Ahokas AA, de Bodinat C. Efficacy of agomelatine in generalized anxiety disorder: A randomized, double blind, placebo-controlled study. J Clin Psychopharmacol. 2008;28(5):561-6. DOI: https://doi.org/10.1097/JCP.0b013e318184ff5b

Stein DJ, Ahokas A, Albarran C. Agomelatine prevents relapse in generalized anxiety disorder: A 6-month randomized, double-blind, placebo-controlled discontinuation study. J Clin Psychiatry. 2012;73(7):1002-8. DOI: https://doi.org/10.4088/JCP.11m07493

Stein DJ, Picarel-Blanchot F, Kennedy SH. Efficacy of the novel antidepressant agomelatine for anxiety symptoms in major depression. Hum Psychopharmacol. 2013;28(2):151–9. DOI: https://doi.org/10.1002/hup.2294

De Berardis D, Conti CM, Marini S. Is there a role for agomelatine in the treatment of anxiety disorders. A review of published data. Int J Immunopathol Pharmacol. 2013;26(2):299–304. DOI: https://doi.org/10.1177/039463201302600203

BrBremner JD, Krystal JH, Southwick SM, Charney DS. Noradrenergic mechanisms in stress and anxiety: I. preclinical studies. Synapse. 1996;23(1):28–38. DOI: https://doi.org/10.1002/(SICI)1098-2396(199605)23:1<28::AID-SYN4>3.3.CO;2-4

Bremner JD, Krystal JH, Southwick SM, Charney DS. Noradrenergic mechanisms in stress and anxiety: II. clinical studies. Synapse. 1996;23(1):39–51. DOI: https://doi.org/10.1002/(SICI)1098-2396(199605)23:1<39::AID-SYN5>3.3.CO;2-Y

Pfau ML, Russo SJ. Peripheral and central mechanisms of stress resilience. Neurobiol Stress. 2015;1:66–79. DOI: https://doi.org/10.1016/j.ynstr.2014.09.004

Arnsten AF, Raskind MA, Taylor FB, Connor DF. The effects of stress exposure on prefrontal cortex: Translating basic research into successful treatments for post-traumatic stress disorder. Neurobiol Stress. 2015;1:89–99. DOI: https://doi.org/10.1016/j.ynstr.2014.10.002

Neylan TC, Lenoci M, Samuelson KW. No improvement of posttraumatic stress disorder symptoms with guanfacine treatment. Am J Psychiatry. 2007;164(2):298–305.

Davis LL, Ward C, Rasmusson A. A placebo-controlled trial of guanfacine for the treatment of posttraumatic stress disorder in veterans. Psychopharmacol Bull. 2008;41(1):8–18. DOI: https://doi.org/10.64719/pb.4275

Connor DF, Grasso DJ, Slivinsky MD. An open-label study of guanfacine extended release for traumatic stress related symptoms in children and adolescents. J Child Adolesc Psychopharmacol. 2013;23(4):244–51. DOI: https://doi.org/10.1089/cap.2012.0119

Colombo G, Maccioni P, Vargiolu D. The dopamine beta-hydroxylase inhibitor, nepicastat, reduces different alcohol-related behaviors in rats. Alcohol Clin Exp Res. 2014;38(9):2345–53. DOI: https://doi.org/10.1111/acer.12520

Starcevic V. Benzodiazepines for anxiety disorders: maximising the benefits and minimising the risks. Adv Psychiatr Treat. 2012;18(4):250–8. DOI: https://doi.org/10.1192/apt.bp.110.008631

Quagliato LA, Freire RC, Nardi AE. Risks and benefits of medications for panic disorder: a comparison of SSRIs and benzodiazepines. Expert Opin Drug Saf. 2018;4;17(3):315–24. DOI: https://doi.org/10.1080/14740338.2018.1429403

Edinoff AN, Akuly HA, Hanna TA, Ochoa CO, Patti SJ, Ghaffar YA, Kaye AD, Viswanath O, Urits I, Boyer AG, Cornett EM, Kaye AM. Selective serotonin reuptake inhibitors and adverse effects: A narrative review. Neurol Int. 2021;5;13(3):387–401. DOI: https://doi.org/10.3390/neurolint13030038

Kent JM, Coplan JD, Gorman JM. Clinical utility of the selective serotonin reuptake inhibitors in the spectrum of anxiety. Biological Psychiatry (Internet). 1998;1;44(9):812–24. DOI: https://doi.org/10.1016/S0006-3223(98)00210-8

Dell'Osso B, Buoli M, Baldwin DS, Altamura AC. Serotonin norepinephrine reuptake inhibitors (SNRIs) in anxiety disorders: a comprehensive review of their clinical efficacy. Hum Psychopharmacol. 2010;25(1):17-29. DOI: https://doi.org/10.1002/hup.1074

Wilson TK, Tripp J. Buspirone. (Updated 2023 Jan 17). In: StatPearls (Internet). Treasure Island (FL): StatPearls Publishing. 2023.

Noyes R. Beta-blocking drugs and anxiety. Psychosomatics. 1982;23(2):155–70. DOI: https://doi.org/10.1016/S0033-3182(82)73433-4

Belkin M, Schwartz T. Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder. Drugs Context. 2015;4:1–5. DOI: https://doi.org/10.7573/dic.212286

Garakani A, Freire RC, Buono FD, Thom RP, Larkin K, Funaro MC, Salehi M, Perez-Rodriguez MM. An umbrella review on the use of antipsychotics in anxiety disorders: A registered report protocol. PLoS One. 2022;17(6):269772. DOI: https://doi.org/10.1371/journal.pone.0269772

Downloads

Published

2025-10-24

How to Cite

Rajesham, V. V., Nandini, A. S., Nandini, A. S., Behera, A., & Rao, T. R. (2025). Pharmacological breakthroughs in anxiety management: exploring traditional and emerging therapies. International Journal of Basic & Clinical Pharmacology, 14(6), 1032–1044. https://doi.org/10.18203/2319-2003.ijbcp20253381