Generalized anxiety disorder: diagnosis and therapy issues
https://doi.org/10.51793/OS.2025.28.11.005
Abstract
Background. Generalized anxiety disorder is characterized by constant, excessive, and unfounded worry about everyday things. It is extremely difficult to control and is often accompanied by a variety of nonspecific psychological and physical symptoms. Without proper treatment, generalized anxiety disorder becomes chronic. Its manifestations are complicated by comorbidity with other mental disorders, which further worsen the outcome and contribute to poor response to treatment.
Results. The review covers the epidemiology of generalized anxiety disorder, the formation of the concept, representation in modern classifications of mental disorders, diagnostic criteria, comorbidity issues, approaches to the treatment of generalized anxiety disorder with an emphasis on psychopharmacotherapy, including the features of the treatment of generalized anxiety in old age. It has been demonstrated that generalized anxiety is one of the most common mental disorders, often beginning in adolescence, characterized by a chronic course. Generalized anxiety is characterized by high comorbidity with other mental disorders, including depression, panic disorder and addictions. The review presents the evolution of the definition of the disorder in the DSM classifications, describes the diagnostic criteria for generalized anxiety disorder in the ICD. Consideration of generalized anxiety from the standpoint of RDoC is discussed. The article provides a detailed description of the use of antidepressants, buspirone and benzodiazepines, atypical antipsychotics and mood stabilizers in generalized anxiety disorder. Particular attention is paid to a new domestic non-benzodiazepine anxiolytic, licensed for use in generalized anxiety disorder and included in the Clinical Guidelines Aviandr (maritupirdine). General principles of psychopharmacotherapy of generalized anxiety are given.
About the Author
N. N. Petrova
Saint Petersburg State University
Россия
Россия
Nataliia N. Petrova, Dr. of Sci. (Med.), Professor, Senior Research Fellow, Psychiatrist of the Highest Category, Honored Worker of Higher Professional Education of the Russian Federation, Chairman of the Board of the Bekhterev Psychiatric Society of St. Petersburg, member of the Board of the Russian Psychiatric Society, Head of the Department of Psychiatry and Narcology at the Medical Institute
7-9 Universitetskaya Naberezhnaya, Saint Petersburg, 199034
References
1. Munir S., Takov V. Generalized Anxiety Disorder. 2022 Oct 17. In: Stat Pearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. PMID: 28722900.
2. Wittchen H. U., Jacobi F. Size and burden of mental disorders in Europe – a critical review and appraisal of 27 studies. Eur Neuropsychopharmacoi. 2005; 15 (4): 357-376. DOI: 10.1016/j.euroneuro.2005.04.012.
3. Baldaçara L., Paschoal A. B., Pinto A. F., Loureiro F. F., Antonio L. A. V. G., Veiga D. L., Almeida T. M., Dos Santos D. C., Malloy-Diniz L. F., de Mello M. F., de Mello A. F., Sanches M., Gandarela L. M., Bernik M. A., Nardi A. E., da Silva A. G., Uchida R. R. Brazilian Psychiatric Association treatment guidelines for generalized anxiety disorder: perspectives on pharmacological and psychotherapeutic approaches. Braz J Psychiatry. 2024; 46: e20233235. DOI: 10.47626/15164446-2023-3235. Epub 2023 Nov 13. PMID: 37956131; PMCID: PMC11302992.
4. I nstitute for Health Metrics and Evaluation (IHME). Global health data exchange, discover the world's health data. 2019. ghdx.healthdata.org/gbd-results-tool.
5. Mal K., Awan I. D., Ram J., Shaukat F. Depression and anxiety as a risk factor for myocardial infarction. Cureus. 2019; 11: e6064.
6. Chen T. R., Huang H. C., Hsu J. H., Ouyang W. C., Lin K. C. Pharmacological and psychological interventions for generalized anxiety disorder in adults: a network meta-analysis. J Psychiatr Res. 2019; 118: 73-83.
7. Silva M. T., Caicedo Roa M., Martins S. S., da Silva A. T. C., Galvao T. F. Generalized anxiety disorder and associated factors in adults in the Amazon, Brazil: A population-based study. J Affect Disord. 2018; 236: 180-186.
8. Scheeringa M. S, Burns L. C. Generalized Anxiety Disorder in Very Young Children: First Case Reports on Stability and Developmental Considerations. Case Rep Psychiatry. 2018; 2018: 7093178.
9. Ströhle A., Gensichen J., Domschke K. The Diagnosis and Treatment of Anxiety Disorders. Dtsch Arztebl Int. 2018; 155 (37): 611-620.
10. Leonard K., Abramovitch A. Cognitive functions in young adults with generalized anxiety disorder. Eur Psychiatry. 2019; 56: 1-7.
11. Roomruangwong C., Simeonova D. S., Stoyanov D. S., Anderson G., Carvalho A., Maes M. Common Environmental Factors May Underpin the Comorbidity Between Generalized Anxiety Disorder and Mood Disorders Via Activated Nitro-oxidative Pathways. Curr Top Med Chem. 2018; 18 (19): 1621-1640.
12. Grenier S., Desjardins F., Raymond B., Payette M. C., Rioux M. È., Landreville P., Gosselin P., Richer M. J., Gunther B., Fournel M., Vasiliadis H. M. Six-month prevalence and correlates of generalized anxiety disorder among primary care patients aged 70 years and above: Results from the ESA-services study. Int J Geriatr Psychiatry. 2019; 34 (2): 315-323.
13. Beesdo-Baum K., Knappe S. Developmental epidemiology of anxiety disorders. Child and Adolescent Psychiatric Clinics of North America. 2012; 21: 457-478. 10.1016/j.chc.2012.05.001.
14. Beesdo K., Knappe S., Pine D. S. Anxiety and anxiety disorders in children and adolescents: Developmental issues and implications for DSM-V. Psychiatric Clinics of North America. 2009; 32: 483-524. 10.1016/j.psc.2009.06.002.
15. Nutt D., Argyropoulos S., Hood S., Potokar J. Generalized anxiety disorder: a comorbid disease. Eur Neuropsychopharmacol. 2006; 16 (suppl 2): S109-S118. DOI: 10.1016/j.euroneuro.2006.04.003.
16. Roberge P., Normand-Lauziere F., Raymond I., et al. Generalized anxiety disorder in primary care: mental health services use and treatment adequacy. BMC Earn Pract. 2015; 16: 146. DOI: 10.1186/s12875-015-0358-y.
17. Buoli M., Caldiroli A., Caletti E., et al. New approaches to the pharmacological management of generalized anxiety disorder. Expert Opin Pharmacother. 2013; 14 (2): 175-184. DOI: 10.1517/14656566.2013.759559.
18. Bandelow B., Zohar J., Hollander E., et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders – first revision. World J Biol Psychiatry. 2008; 9 (4): 248-312. DOI: 10.1080/15622970802465807.
19. Pollack M. H. Refractory generalized anxiety disorder. J Clin Psychiatry. 2009; 70 (suppl 2): 32-38. DOI: 10.4088/jcp.s.7002.06.
20. Crocq M. A. The history of generalized anxiety disorder as a diagnostic category. Dialogues Clin Neurosci. 2017; 19 (2): 107-116. DOI: 10.31887/DCNS.2017.19.2/macrocq.
21. Freud S. The Standard Edition of the Complete Psychological Works of Sigmund Freud: (1893-1899) Early psycho-analytic publications. Strachey J., trans. London, UK: The Hogarth Press; 1962: 90ff. The Standard Edition of the Complete Psychological Works of Sigmund Freud; vol 3Freud S. Obsessions et phobies. Rev Neurol. 1895; 3 (2): 33-38.
22. World Health Organization (WHO). International classification of diseases. 11th Revision (ICD-11) [Internet]. 2018. www.who.int/standards/ classifications/classification-of-diseases
23. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013.
24. Bomyea J., Ramsawh H., Ball T. M., et al. Intolerance of uncertainty as a mediator of reductions in worry in a cognitive behavioral treatment program for generalized anxiety disorder. J Anxiety Disord. 2015; 33: 90-94. DOI: 10.1016/j.janxdis.2015.05.004.
25. Gorwood P. Generalized anxiety disorder and major depressive disorder comorbidity: an example of genetic pleiotropy? Eur Psychiatry. 2004; 19 (1): 27-33. DOI: 10.1016/j.eurpsy.2003.10.002.
26. Watson D. Rethinking the mood and anxiety disorders: a quantitative hierarchical model for DSM-IV. J Abnorm Psychol. 2005; 114 (4): 522-536. DOI: 10.1037/0021-843X.114.4.522.
27. Kessler R. C., Gruber M., Hettema J. M., Hwang I., Sampson N., Yonkers K. A. Co-morbid major depression and generalized anxiety disorders in the National Comorbidity Survey follow-up. Psychol Med. 2008; 38 (3): 365-374. DOI: 10.1017/S0033291707002012.
28. Rickels K., Rynn M. Overview and clinical presentation of generalized anxiety disorder. Psychiatr Clin North Am. 2001; 24 (1): 1-17. DOI: 10.1016/s0193953x(05)70203-3.
29. Kogan C. S., Stein D. J., Maj M., First M. B., Emmelkarnp P. M., Reed G. M. The classification of anxiety and fear-related disorders in the ICD-11. Depress Anxiety. 2016; 33 (12): 1141-1154. DOI: 10.1002/da.22530.
30. Watson D., Stanton K., Clark L. A. Self-report indicators of negative valence constructs within the research domain criteria (RDoC): a critical review. J Affect Disord. 2016 Oct 28. Epub ahead of print. DOI: 10.1016/j.jad.2016.09.065.
31. Engels A. S., Heller W., Mohanty A., et al. Specificity of regional brain activity in anxiety types during emotion processing. Psychophysiology. 2007; 44 (3): 352-363. DOI: 10.1111/j.1469-8986.2007.00518.x.
32. Seok J. Generalized Anxiety Disorder Misdiagnosed as Nonspecific Physical Pain. In: Tohid H., Baratta L. G., Maibach H. (eds.). The Misdiagnosis Casebook in Clinical Medicine. Springer, Cham. 2023. https://DOI.org/10.1007/978-3-031-28296-6_63.
33. Showraki M., Showraki T., Brown K. Generalized Anxiety Disorder: Revisited. Psychiatr Q. 2020; 91 (3): 905-914. DOI: 10.1007/s11126-020-09747-0. PMID: 32383134.
34. Mishra A. K., Varma A. R. A Comprehensive Review of the Generalized Anxiety Disorder. Cureus. 2023; 15 (9): e46115. DOI: 10.7759/cureus.46115. PMID: 37900518; PMCID: PMC10612137.
35. B aldwin D. S., Ajel K. I., Garner M. Curr Pharmacological treatment of generalized anxiety disorder. Top Behav Neurosci. 2010; 2: 453-467. DOI: 10.1007/7854_2009_2.
36. He H., Xiang Y., Gao F., Bai L., Gao F., Fan Y., et al. Comparative efficacy and acceptability of first-line drugs for the acute treatment of generalized anxiety disorder in adults: a network meta-analysis. J Psychiatr Res. 2019; 118: 21-30.
37. Li X., Zhu L., Su Y., Fang S. Short-term efficacy and tolerability of venlafaxine extended release in adults with generalized anxiety disorder without depression: a meta-analysis. PLoS One. 2017; 12: e0185865.
38. Baldwin D. S., Woods R., Lawson R., Taylor D. Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis. BMJ. 2011; 342: d1199. 10.1136/bmj.d119.
39. Strawn J. R., Geracioti L., Rajdev N., Clemenza K., Levine A. Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidencebased treatment review. Expert Opin Pharmacother. 2018; 19: 1057-1070. DOI: 10.1080/14656566.2018.1491966.
40. Mavranezouli I., Meader N., Cape J., Kendall T. The cost effectiveness of pharmacological treatments for generalized anxiety disorder. Pharmacoeconomics. 2013; 31: 317-333. DOI: 10.1007/s40273-013-0031-z.
41. Bourin M., Chue P., Guillon Y. Paroxetine: a review. CNS Drug Rev. 2001; 7: 25-47. DOI: 10.1111/j.1527-3458.2001.tb00189.x.
42. Stein D. J., Khoo J. P., Ahokas A., Jarema M., van Ameringen M., Vavrusova L., et al. 12-week double-blind randomized multicenter study of efficacy and safety of agomelatine (25-50 mg/day) versus escitalopram (10-20 mg/day) in out-patients with severe generalized anxiety disorder. Eur Neuropsychopharmacol. 2018; 28: 970-979.
43. Buoli M., Grassi S., Serati M., Altamura A. C. Agomelatine for the treatment of generalized anxiety disorder. Expert Opin Pharmacother. 2017; 18 (13): 1373-1379. DOI: 10.1080/14656566.2017.1359257. Epub 2017 Jul 28. PMID: 28730851.
44. Haddad M., Dieckmann L. H. J., Viola T. W., de Araújo M. R., da Silva N. R., Mari J. J. The Efficacy of Fluvoxamine in Anxiety Disorders and ObsessiveCompulsive Disorder: An Overview of Systematic Reviews and Meta-Analyses. Pharmaceuticals (Basel). 2025; 18 (3): 353. DOI: 10.3390/ph18030353. PMID: 40143130; PMCID: PMC11944676.
45. Baldwin D. S., den Boer J. A., Lyndon G., Emir B., Schweizer E., Haswell H. Efficacy and safety of pregabalin in generalized anxiety disorder: a critical review of the literature. Journal of Psychopharmacology 2015; 29: 1047-1060. 10.1177/0269881115598411.
46. Schjerning O., Rosenzweig M., Pottegard A., Damkier P., Nielsen J. Abuse potential a pregabalin: a systematic review. CNS Drugs. 2016; 30: 9-25. 10.1007/s40263-015-0303-6.
47. Davidson J. R. Use of benzodiazepines in social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder. J Clin Psychiatry. 2004; 65 Suppl 5: 29-33. PMID: 15078116.
48. Baldwin D. S., Aitchison K., Bateson A., et al. Benzodiazepines: risks and benefits. A reconsideration. Journal of Psychopharmacology 2013; 27: 967-971. 10.1177/0269881113503509.
49. Howland R. H. Buspirone: back to the future. J Psychosoc Nurs Ment Health Serv. 2015; 53: 21-24. DOI: 10.3928/02793695-20151022-01.
50. Buoli M., Caldiroli A., Caletti E., et al. New approaches to the pharmacological management of generalized anxiety disorder. Expert Opin Pharmacother, 2013; 14 (2): 175-184. DOI: 10.1517/14656566.2013.759559.
51. Maneeton N., Maneeton B., Woottiluk P., Likhitsathian S., Suttajit S., Boonyanaruthee V., et al. Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2016; 10: 259-76.
52. Morozova M. A., Safarova T. P., Gluskin L. Ya., Penchul N. A., Kasimova L. N., Zayarnaya I. I., Boychevskaya Yu. O., Shiryaev O. Yu., Reznikov M. K., Bukhanovskaya O. A., Mavani D. Ch., Reutova M. A., Nekrasov V. A., Gorchakov D. S., Balakin K. V., Tarakhanova A. S., Yakubova E. V. Double-blind placebo-controlled study of the efficacy and tolerability of AviandrR in the treatment of generalized anxiety disorder. Sovremennaia terapiya psikhicheskikh rasstroistv. 2024; 3: 2-16. DOI: 10.21265/ PSYPH.2024.82.78.001 (In Russ.)
53. Stefan S., Cristea I. A., Szentagotai Tatar A., David D. Cognitive-behavioral therapy (CBT) for generalized anxiety disorder: contrasting various CBT approaches in a randomized clinical trial. J Clin Psychol. 2019; 75: 1188-1202. DOI: 10.1002/jclp.22779.
54. Cuijpers P., Sijbrandij M., Koole S., Huibers M., Berking M., Andersson G. Psychological treatment of generalized anxiety disorder: a meta-analysis. Clinical Psychology Review. 2014; 34: 130-40. 10.1016/j.cpr.2014.01.002.
55. Kishita N., Laidlaw K. Cognitive behavior therapy for generalized anxiety disorder: is CBT equally efficacious in adults of working age and older adults? Clinical Psychological Review. 2017; 52: 124-36. 10.1016/j.cpr.2017.01.003.
56. Baldwin D. S., Anderson I. M., Nutt D. J., et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessivecompulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. Journal of Psychopharmacology. 2014; 28: 403-439. 10.1177/0269881114525674.
57. Montgomery S. A., Lyndon G., Almas M., Whalen E., Prieto R. Early improvement with pregabalin predicts endpoint response in patients with generalized anxiety disorder: an integrated and predictive data analysis. Int Clin Psychopharmacol. 2017; 32: 41-48.
58. Bandelow B., Reitt M., Rover C., Michaelis S., Gorlich Y., Wedekind D. Efficacy of treatments for anxiety disorders: a meta-analysis. Int Clin Psychopharmacol. 2015; 30: 183-192.
59. Loerinc A. G., Meuret A. E., Twohig M. P., et al. Response rates for CBT for anxiety disorders: need for standardized criteria. Clin Psychol Rev. 2015; 42: 72-82.
60. Solis E. C., van Hemert A. M., Carlier I. V. E., et al. The 9-year clinical course of depressive and anxiety disorders: new NESDA findings. J Affect Disord 2021; 295: 1269-1279.
61. Samuel M., Zimovetz E. A., Gabriel Z., Beard S. M. Efficacy and safety of treatments for refractory generalized anxiety disorder: a systematic review. Int Clin Psychopharmacol. 2011; 26: 63-68.
62. Chen A., Metzger E., Lee S., Osser D. A. Proposed Algorithm for the Pharmacological Treatment of Generalized Anxiety Disorder in the Older Patient. J Geriatr Psychiatry Neurol. 2025; 38 (3): 155-171. DOI: 10.1177/08919887241289533. Epub 2024 Oct 1. PMID: 39352792.
63. Latas M., Trajković G., Bonevski D., Naumovska A., Vučinić Latas D., Bukumirić Z., Starčević V. Psychiatrists' treatment preferences for generalized anxiety disorder. Hum Psychopharmacol. 2018; 33 (1). DOI: 10.1002/hup.2643.
Review
For citations:
Petrova N.N. Generalized anxiety disorder: diagnosis and therapy issues. Lechaschi Vrach. 2025;1(11):44-52. (In Russ.) https://doi.org/10.51793/OS.2025.28.11.005
Views:
48
JATS XML
Email this article 
