Rational Short-Term Therapy for Anxiety and Asthenic States: Epidemiological and Diagnostic Rationale

Subthreshold anxiety and asthenic states account for a significant proportion of consultations with family physicians, general practitioners, and neurologists; however, their prognoses, and, consequently, the optimal scope of therapy, differ substantially. This article systematizes current epidemiological data regarding the 3-year course of subthreshold anxiety and subthreshold depression (based on the NEMESIS-2 cohort), outlines key criteria for the differential diagnosis of asthenia, adjustment disorders, and anxiety/depressive disorders, and examines the evidence base regarding the role and limitations of short-term anxiolytic therapy. It is demonstrated that for conditions with a favorable prognosis, a brief, time-limited course of anxiolytics provides rapid symptomatic relief without the need to prematurely initiate long-term (multi-month) maintenance therapy. Conversely, when treatment with antidepressants is indicated, the short-term addition of an anxiolytic during the early phase, according to a systematic review by Y. Ogawa et al. (2019), is associated with an improved therapeutic response and better tolerability. A practical patient management algorithm is proposed, along with rational parameters for short-term therapy: limiting the duration of the course (typically to 4 weeks), ensuring it is combined with ongoing clinical monitoring, and implementing a gradual withdrawal of the medication.

References

1. American Psychiatric Association (2022) Diagnostic and Statistical Manual of Mental Disorders. 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Association Publishing.
2. Всесвітня організація охорони здоров’я (1992) Міжнародна класифікація хвороб 10-го перегляду (МКХ-10). Клас V: Психічні та поведінкові розлади. Клінічні описи та діагностичні вказівки. Женева: ВООЗ.
3. Bosman R.C., Ten Have M., de Graaf R. et al. (2019) Prevalence and course of subthreshold anxiety disorder in the general population: a three-year follow-up study. J. Affect. Disord., 247: 105–113. doi.org/10.1016/j.jad.2019.01.018.
4. Zhang R., Peng X., Song X. et al. (2023) The prevalence and risk of developing major depression among individuals with subthreshold depression in the general population. Psychol. Med., 53(8): 3611–3620. doi.org/10.1017/S0033291722000241. Erratum in: Psychol. Med., 55: e184 (2025). doi.org/10.1017/S0033291725100937.
5. Tuithof M., Ten Have M., van Dorsselaer S. et al. (2018) Course of subthreshold depression into a depressive disorder and its risk factors. J. Affect. Disord., 241: 206–215. doi.org/10.1016/j.jad.2018.08.010.
6. Інструкція для медичного застосування лікарського засобу Гідазепам ІС^® (реєстраційні посвідчення UA/8579/01/02, UA/8579/02/01-02). ТОВ «ІнтерХім». compendium.com.ua/dec/273792.
7. Міщенко Т.С., Забродіна Л.П., Міщенко В.М., Бовт Ю.В. (2025) Препарат Гідазепам ІС^® у практиці невролога, психіатра та нарколога: сучасні уявлення про механізми дії, клінічне застосування та перспективи. Міжнар. неврол. журн., 21(3): 58–67. mif-ua.com/archive/article/54501.
8. Cipriani A., Furukawa T.A., Salanti G. et al. (2018) Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet, 391(10128): 1357–1366. doi.org/10.1016/S0140-6736(17)32802-7.
9. Sinclair L.I., Christmas D.M., Hood S.D. et al. (2009) Antidepressant-induced jitteriness/anxiety syndrome: systematic review. Br. J. Psychiatry, 194(6): 483–490. doi.org/10.1192/bjp.bp.107.048371.
10. Olfson M., Marcus S.C., Tedeschi M., Wan G.J. (2006) Continuity of antidepressant treatment for adults with depression in the United States. Am. J. Psychiatry, 163(1): 101–108. doi.org/10.1176/appi.ajp.163.1.101.
11. Montejo A.L., Llorca G., Izquierdo J.A., Rico-Villademoros F. (2001) Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. J. Clin. Psychiatry, 62(Suppl. 3): 10–21.
12. Goodwin G.M., Price J., De Bodinat C., Laredo J. (2017) Emotional blunting with antidepressant treatments: a survey among depressed patients. J. Affect. Disord., 221: 31–35. doi.org/10.1016/j.jad.2017.05.048.
13. Gafoor R., Booth H.P., Gulliford M.C. (2018) Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study. BMJ, 361: k1951. doi.org/10.1136/bmj.k1951.
14. Coupland C., Dhiman P., Morriss R. et al. (2011) Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ, 343: d4551. doi.org/10.1136/bmj.d4551.
15. Laporte S., Chapelle C., Caillet P. et al. (2017) Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: a meta-analysis of observational studies. Pharmacol. Res., 118: 19–32.
16. Anglin R., Yuan Y., Moayyedi P. et al. (2014) Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis. Am. J. Gastroenterol., 109(6): 811–819. doi.org/10.1038/ajg.2014.82.
17. Boyer E.W., Shannon M. (2005) The serotonin syndrome. N. Engl. J. Med., 352(11): 1112–1120.
18. Stone M., Laughren T., Jones M.L. et al. (2009) Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ, 339: b2880. doi.org/10.1136/bmj.b2880.
19. Henssler J., Schmidt Y., Schmidt U. et al. (2024) Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. Lancet Psychiatry, 11(7): 526–535. doi.org/10.1016/S2215-0366(24)00133-0.
20. Horowitz M.A., Taylor D. (2019) Tapering of SSRI treatment to mitigate withdrawal symptoms. Lancet Psychiatry, 6(6): 538–546.
21. Fournier J.C., DeRubeis R.J., Hollon S.D. et al. (2010) Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA, 303(1): 47–53.
22. National Institute for Health and Care Excellence (2022) Depression in adults: treatment and management. NICE guideline [NG222]. London, NICE.
23. Rush A.J., Trivedi M.H., Wisniewski S.R. et al. (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am. J. Psychiatry, 163(11): 1905–1917.
24. Ogawa Y., Takeshima N., Hayasaka Y. et al. (2019) Antidepressants plus benzodiazepines for adults with major depression. Cochrane Database Syst. Rev., 6(6): CD001026. doi.org/10.1002/14651858.CD001026.pub2.
25. Joint Formulary Committee (2024) British National Formulary (BNF). London: BMJ Group and Pharmaceutical Press. Available at: bnf.nice.org.uk.
26. Baldwin D.S., Aitchison K., Bateson A. et al. (2013) Benzodiazepines: risks and benefits. A reconsideration. J. Psychopharmacol., 27(11): 967–971. doi.org/10.1177/0269881113503509.