The Pharmacologic Treatment of Anxiety Disorders: A Review of Progress
Abstract
Anxiety disorders, as a group, are among the most common mental health conditions and frequently cause significant functional impairment. Both psychotherapeutic and pharmacologic techniques are recognized to be effective management strategies. This review provides a discussion of the major classes of psychotropic medications investigated in clinical trials of the following anxiety disorders: panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder. Findings suggest that both selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are useful first-line agents for most of the anxiety disorders, particularly given the frequent comorbidity with mood disorders. Highly serotonergic agents are preferred for obsessive-compulsive disorder. Other antidepressants, such as tricyclic antidepressants or monoamine oxidase inhibitors, are generally reserved as second- and third-line strategies due to tolerability issues. Evidence for other agents, including anticonvulsants and atypical antipsychotics, suggests that they may have an adjunctive role to antidepressants in cases of treatment resistance, while azapirones have been used effectively for generalized anxiety disorder, and a substantial body of evidence supports benzodiazepine use in panic disorder and generalized anxiety disorder. Despite notable advances, many patients with anxiety disorders fail to adequately respond to existing pharmacologic treatments. Increased research attention should be focused on systematizing pharmacologic and combined pharmacologic-psychosocial strategies to address treatment resistance and developing novel treatments for anxiety disorders.
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The serotonin system is the most widely used pharmacological target for treating depression and anxiety.
“It is the most widely used pharmacological target for treating depression and anxiety (Belmaker and Agam, 2008; Ravindran and Stein, 2010)”
From Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems (2018) · cites this paper as Ravindran and Stein, 2010
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Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems
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“It is the most widely used pharmacological target for treating depression and anxiety (Belmaker and Agam, 2008; Ravindran and Stein, 2010), and depression has become the leading cause of disability worldwide (World Health Organization, 2017).”
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“Antidepressants are approved for the treatment of depression and several other mental disorders, including generalized anxiety disorder [2], panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder [3].”
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“The reagents strengthening the efficacy of their interactions were applied for the psychotropic medication of anxiety disorders, such as selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors and benzodiazepine [66].”
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“Over the past 3 decades, a wealth of evidence from RCTs has accumulated, supporting the short-term efficacy of both pharmacologic and CBTs of the 5 major anxiety disorders (PD, GAD, SAD, OCD, and PTSD) (Ravindran and Stein, 2010).”
BackgroundInfluentialDiagnosis and Treatment of Major Depressive Disorder
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“However, most patients with anxiety disorders experience a progressive reduction of their symptoms with continuous use of selective serotonin reuptake inhibitors (SSRIs) and immediate symptom relief with benzodiazepines (BDZ), as diazepam (DZP) (Ravindran and Stein, 2010).”
Thinking small: towards microRNA-based therapeutics for anxiety disorders
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BackgroundAssociation of Variations in TPH1 and HTR2B with Gestational Weight Gain and Measures of Obesity
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“…Neuroscience Societies and Blackwell Publishing Ltd European Journal of Neuroscience, 36, 3531–3537 et al., 2001; Zanoveli et al., 2005), clomipramine and fluoxetine (Poltronieri et al., 2003), drugs that are clinically used to treat panic diseases (Ravindran & Stein, 2010; Freire et al., 2011).”
BackgroundAltered Uncinate Fasciculus Microstructure in Childhood Anxiety Disorders in Boys But Not Girls
Tromp, D., Williams, L. E., Fox, A. S., Oler, J. A., Roseboom, P. H., Rogers, G. M., Benson, B. E., Alexander, A. L., Pine, D. S., & Kalin, N. H. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.18040425 · Cited by 49 · see citing works
“Establishing a better understanding of the pathophysiology of childhood anxiety disorders will facilitate the development of novel, more effective treatments (10).”
MAOA, DBH and SLC6A4 variants in CHARGE: A case control study of autism spectrum disorders
Tassone, F., Qi, L., Zhang, W., Hansen, R. L., Pessah, I. N., & Hertz-Picciotto, I. (2011) · Autism Research · doi:10.1002/aur.196 · Cited by 52 · see citing works
“Finally, environmental factors could be interacting with the different allelic variants to play a role in the behavioral outcomes; in support of this possibility, a number of common environmental factors affect MAOA, such as pesticides [Rao & Rao, 1993] and medications [Ravindran & Stein, 2010].”
BackgroundTomić, M., Ignjatović, Đ., Tovilović-Kovačević, G., Krstić‐Milošević, D., Ranković, S., Popović, T., & Glibetić, M. (2016) · Food & Function · doi:10.1039/c6fo00321d · Cited by 47 · see citing works
Plants of the Genus Lavandula : From Farm to Pharmacy
Salehi, B., Mnayer, D., Özçelik, B., Altın, G., Kasapoğlu, K. N., Daşkaya-Dikmen, C., Sharifi‐Rad, M., Selamoğlu, Z., Acharya, K., Sen, S., et al. (2018) · Natural Product Communications · doi:10.1177/1934578x1801301037 · Cited by 46 · see citing works
“Current clinical treatments for anxiety disorders are effective, however, a wide range of adverse effects may take place [208, 209] as well as pharmacokinetic interactions with other drugs [210].”
BackgroundLi, W., Chen, R., Feng, L., Dang, X., Liu, J., Chen, T., Yang, J., Su, X., Lv, L., Li, T., et al. (2023) · Nature Human Behaviour · doi:10.1038/s41562-023-01746-y · Cited by 47 · see citing works
Effect of Lemongrass Aroma on Experimental Anxiety in Humans
Goes, T. C., Carvalho, F. U. R., Almeida-Souza, T. H., Alves, P. B., & Teixeira-Silva, F. (2015) · The Journal of Alternative and Complementary Medicine · doi:10.1089/acm.2015.0099 · Cited by 46 · see citing works
“In addition, not all patients benefit from the available treatments and only a few of them reach complete recovery.(3,4) These facts have justified a growing demand for alternative or complementary procedures for the relief of anxiety symptoms, both by health professionals and the general population.”
Manzo, L., Donaire, R., Sabariego, M., Papini, M. R., & Torres, C. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.09.017 · Cited by 45 · see citing works
Role of MicroRNAs in Anxiety and Anxiety-Related Disorders
Murphy, C. P., & Singewald, N. (2019) · Current topics in behavioral neurosciences · doi:10.1007/7854_2019_109 · Cited by 48 · see citing works
Enhancing a declarative memory in humans: The effect of clonazepam on reconsolidation
Rodríguez, M. L. C., Campos, J., Forcato, C., Leiguarda, R., Maldonado, H., Molina, V. A., & Pedreira, M. E. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.06.059 · Cited by 41 · see citing works
“…in the pathogenesis of anxiety disorders (Enna, 1984; Khozhenko, 2009; Kowalski et al., 2007; Lydiard, 2003), therefore, increasing GABAergic neurotransmission by means of benzodiazepine administration is widely accepted as an effective treatment for anxiety disorders (Ravindran and Stein, 2010).”
Espadaler, J., Tuson, M., López-Ibor, J. M., Lopez-Ibor, F., & López‐Ibor, M. I. (2016) · CNS Spectrums · doi:10.1017/s1092852915000711 · Cited by 42 · see citing works
Depressive Symptom Network Associated With Comorbid Anxiety in Late-Life Depression
An, M. H., Park, S. S., You, S. C., Park, R. W., Park, B., Woo, H. K., Kim, H. K., & Son, S. J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00856 · Cited by 41 · see citing works
Ketamine and neuroticism: a double-hit hypothesis of internalizing disorders
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“…Schweizer and Bielski (2011), Gray and McNaughton (2000), McNaughton (2002), Pande et al. (2004), Ravindran, Kim, Letamendi and Stein (2009), Ravindran & Stein (2010), Rickels and Rynn (2002), Spivak et al. (2006), Stein, Hollander, Mullen, DeCaria and Liebowitz (1992), Stein, Vythilingum…”
BackgroundMethylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model
Aga‐Mizrachi, S., Cymerblit‐Sabba, A., Gurman, O., Balan, A., Shwam, G., Deshe, R., Miller, L., Gorodetsky, N., Heinrich, N., Tzezana, O., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.82 · Cited by 41 · see citing works
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Threat imminence dictates the role of the bed nucleus of the stria terminalis in contextual fear
Goode, T. D., Acca, G. M., & Maren, S. (2019) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2019.107116 · Cited by 36 · see citing works
Burkhouse, K. L., Jimmy, J., DeFelice, N., Klumpp, H., Ajilore, O., Hosseini, B., Fitzgerald, K. D., Monk, C. S., & Phan, K. L. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0575-5 · Cited by 39 · see citing works
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Sartori, S. B., Maurer, V., Murphy, C. P., Schmuckermair, C., Muigg, P., Neumann, I. D., Whittle, N., & Singewald, N. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv128 · Cited by 37 · see citing works
“Diverse interventions are available for their treatment with significant advances in the last decades (Ravindran and Stein, 2010).”
BackgroundLi, X., Zhong, H., Wang, Z., Xiao, R., Antonson, P., Liu, T., Chuan, W., Zou, J., Wang, L. Y., Nalvarte, I., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01139-5 · Cited by 37 · see citing works
“Anxiety, a very prevalent psychiatric disorder, is an emotional response characterized by excessive fear and avoidance in the absence of real danger [1].”
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Asgharian, P., Quispe, C., Herrera‐Bravo, J., Sabernavaei, M., Hosseini, K., Forouhandeh, H., Ebrahimi, T., Sharafi-Badr, P., Tarhriz, V., Soofiyani, S. R., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.926607 · Cited by 39 · see citing works
“MDD Citalopram (Celexa) Serotonin reuptake inhibitors (SSRIs) (Fava et al., 2004; Papakostas, 2010; Ravindran and Stein, 2010) Escitalopram (Lexapro)”
BackgroundGray, V., & Hughes, R. N. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.12.023 · Cited by 36 · see citing works
Stein, M. B., Jain, S., Simon, N. M., West, J. C., Marvar, P. J., Bui, É., He, F., Benedek, D. M., Cassano, P., Griffith, J. L., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.05.012 · Cited by 36 · see citing works
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“GAD can be treated successfully, both by psychological therapies (Hunot et al. 2007) and by medications (Ravindran & Stein, 2010; Baldwin et al. 2014).”
BackgroundYadavalli, C. S., Kumar, G. P., Navya, K., Ramya, E. M., & Anilakumar, K. R. (2018) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.13007 · Cited by 34 · see citing works
“Currently, the most widely prescribed medications for anxiety disorders are serotonin reuptake inhibitors (SRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and benzodiazepines (BZDs).([15]) In this study, diazepam (DIZ) was used to compare the anxiolytic activities of the plant extract, as it is known t…”
MethodLeibold, N. K., van den Hove, D., Esquivel, G., Cort, K. D., Goossens, L., Strackx, E., Buchanan, G. F., Steinbusch, H. W. M., Lesch, K., & Schruers, K. R. J. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.04.001 · Cited by 34 · see citing works
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“anxiety disorders in individuals who are partially responsive or nonresponsive to conventional therapy [1,7].”
BackgroundUtilization, Spending, and Price Trends for Benzodiazepines in the US Medicaid Program: 1991-2009
Gorevski, E., Bian, B., Kelton, C. M. L., et al. (2012) · Annals of Pharmacotherapy · doi:10.1345/aph.1q618 · Cited by 32 · see citing works
- Authors
- Ravindran, L. N., & Stein, M. B.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Stein, Murray B.
- ORCID
- Stein, Murray B.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2010-06-11
- Volume
- 71
- Issue
- 07
- Pages
- 839-854
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2045726637
- Cited by
- 317
- References
- 0
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 13 · 2023: 17 · 2022: 17 · 2021: 17 · 2020: 13 · 2019: 24 · 2018: 25 · 2017: 14 · 2016: 26 · 2015: 25 · 2014: 26 · 2013: 21 · 2012: 25
- FWCI
- 33.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH-64122, K24MH064122)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Psychological Treatments and Disorders
- Keywords
- anxiety disorders, pharmacotherapy, panic disorder, social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, antiepileptic drugs, atypical antipsychotics, azapirones, benzodiazepines, treatment resistance
- MeSH terms
- Anticonvulsants, Antidepressive Agents, Anxiety Disorders, Benzodiazepines, Buspirone, Humans, Obsessive-Compulsive Disorder, Phobic Disorders, Psychotropic Drugs, Stress Disorders, Post-Traumatic, Antipsychotic Agents, Randomized Controlled Trials as Topic, Panic Disorder
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