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Current Reviews in Clinical and Experimental Pharmacology

Editor-in-Chief

ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

Clinical Trial

Assessment of the Efficacy of Withania somnifera Root Extract in Patients with Generalized Anxiety Disorder: A Randomized Double-blind Placebo- Controlled Trial

Author(s): Sara Fuladi, Seyed A. Emami, Amir H. Mohammadpour, Asieh Karimani, Ali A. Manteghi* and Amirhossein Sahebkar

Volume 16, Issue 2, 2021

Published on: 13 April, 2020

Page: [191 - 196] Pages: 6

DOI: 10.2174/1574884715666200413120413

Price: $65

Abstract

Background: Anxiety disorders are the most universal psychiatric problems in the general population. Due to their chronic nature, these diseases are managed with a multi-drug regimen lasting for a long period of time. Medication discontinuation leads to 25% and 80% recurrence in the first month and the first year, respectively. Despite several treatment approaches, there is no specific and optimal method for patient management. Therefore, it is necessary to find some new therapeutic approaches with fewer side effects. Withania somnifera is a plant with GABAergic property responsible for its anxiolytic effect. The aim of this study was to investigate the effect of W. somnifera root extract as an alternative therapy to reduce standard Generalized Anxiety Disorder (GAD) symptoms.

Methods: Forty patients who met the inclusion criteria (with a confirmed diagnosis of GAD as stated in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) took part in this randomized double-blind placebo-controlled trial and were randomly selected for participation in the treatment group (W. somnifera extract, 1g/day; n = 22) or the placebo group (n = 18). All patients were under treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) and were prescribed one capsule of the extract or placebo per day for six weeks. The Hamilton anxiety rating scale (HAM-A) was used to assess the severity of GAD symptoms at baseline as well as the second and sixth weeks of the trial.

Results: Comparison of the HAM-A scores during the course of the trial revealed a significant amelioration ofHAM-A score in the treatment group versus placebo (14 and 8 units reduction, respectively (P < 0.05)). Moreover, there was a significant difference in the reduction of GAD score between the second (P =0.04) and sixth week (P =0.02) in the treatment group. The extract was safe and no adverse effect was observed during the trial.

Conclusion: W. somnifera extract offers some potential advantages as a safe and effective adjunctive therapy to SSRIs in GAD. The clinical trial protocol has been registered under the Iranian Registry of Clinical Trials (IRCT20180615040105N1).

Keywords: Withania somnifera, generalized anxiety disorder, randomized controlled trial, Herbal medicine, mental disorder.

Graphical Abstract
[1]
Association AP. Diagnostic and statistical manual of mental disorders; 5th ed. In: Virginia: American Psychiatric Association 2013. 947.
[http://dx.doi.org/10.1176/appi.books.9780890425596]
[2]
Kessler RC, Wang PS. The descriptive epidemiology of commonly occurring mental disorders in the United States. Annu Rev Public Health 2008; 29: 115-29.
[http://dx.doi.org/10.1146/annurev.publhealth.29.020907.090847] [PMID: 18348707]
[3]
Mackenzie CS, Reynolds K, Chou K-L, Pagura J, Sareen J. Prevalence and correlates of generalized anxiety disorder in a national sample of older adults. Am J Geriatr Psychiatry 2011; 19(4): 305-15.
[http://dx.doi.org/10.1097/JGP.0b013e318202bc62] [PMID: 21427639]
[4]
Cuijpers P, Sijbrandij M, Koole S, Huibers M, Berking M, Andersson G. Psychological treatment of generalized anxiety disorder: A meta-analysis. Clin Psychol Rev 2014; 34(2): 130-40.
[http://dx.doi.org/10.1016/j.cpr.2014.01.002] [PMID: 24487344]
[5]
Bereza BG, Machado M, Ravindran AV, Einarson TR. Evidence-based review of clinical outcomes of guideline-recommended pharmacotherapies for generalized anxiety disorder. Can J Psychiatry 2012; 57(8): 470-8.
[http://dx.doi.org/10.1177/070674371205700805] [PMID: 22854029]
[6]
Reinhold JA, Rickels K. Pharmacological treatment for generalized anxiety disorder in adults: An update. Expert Opin Pharmacother 2015; 16(11): 1669-81.
[http://dx.doi.org/10.1517/14656566.2015.1059424] [PMID: 26159446]
[7]
Wilson H, Mannix S, Oko-osi H, Revicki DA. The impact of medication on health-related quality of life in patients with generalized anxiety disorder. CNS Drugs 2015; 29(1): 29-40.
[http://dx.doi.org/10.1007/s40263-014-0217-8] [PMID: 25516469]
[8]
Kapczinski F, dos Santos Souza JJ, Batista Miralha da Cunha AA, Schmitt RR. Antidepressants for Generalised Anxiety Disorder (GAD). Cochrane Libr 2016; 3: CD003592.
[9]
Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y. A randomized, double-blind, fixed-dose study comparing the efficacy and tolerability of vortioxetine 2.5 and 10 mg in acute treatment of adults with generalized anxiety disorder. Hum Psychopharmacol 2014; 29(1): 64-72.
[http://dx.doi.org/10.1002/hup.2371] [PMID: 24424707]
[10]
Chessick CA, Allen MH, Thase M, et al. Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev 2006; 2006(3): CD006115.
[PMID: 16856115]
[11]
Baldwin DS, den Boer JA, Lyndon G, Emir B, Schweizer E, Haswell H. Efficacy and safety of pregabalin in generalised anxiety disorder: A critical review of the literature. J Psychopharmacol (Oxford) 2015; 29(10): 1047-60.
[http://dx.doi.org/10.1177/0269881115598411] [PMID: 26259772]
[12]
Kreys TJM, Phan SV. A literature review of quetiapine for generalized anxiety disorder. Pharmacotherapy 2015; 35(2): 175-88.
[http://dx.doi.org/10.1002/phar.1529] [PMID: 25689246]
[13]
Ravindran LN, Stein MB. The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psychiatry 2010; 71(7): 839-54.
[http://dx.doi.org/10.4088/JCP.10r06218blu] [PMID: 20667290]
[14]
Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: An experimental study. Phytomedicine 2000; 7(6): 463-9.
[http://dx.doi.org/10.1016/S0944-7113(00)80030-6] [PMID: 11194174]
[15]
Chengappa KN, Bowie CR, Schlicht PJ, Fleet D, Brar JS, Jindal R. Randomized placebo-controlled adjunctive study of an extract of withania somnifera for cognitive dysfunction in bipolar disorder. J Clin Psychiatry 2013; 74(11): 1076-83.
[http://dx.doi.org/10.4088/JCP.13m08413] [PMID: 24330893]
[16]
Raut AA, Rege NN, Tadvi FM, et al. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers. J Ayurveda Integr Med 2012; 3(3): 111-4.
[http://dx.doi.org/10.4103/0975-9476.100168] [PMID: 23125505]
[17]
Andrade C, Aswath A, Chaturvedi SK, Srinivasa M, Raguram R. A double-blind, placebo-controlled evaluation of the anxiolytic efficacy ff an ethanolic extract of Withania somnifera. Indian J Psychiatry 2000; 42(3): 295-301.
[PMID: 21407960]
[18]
Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med 2012; 34(3): 255-62.
[http://dx.doi.org/10.4103/0253-7176.106022] [PMID: 23439798]
[19]
Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: A Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med 2011; 8(5)(Suppl.): 208-13.
[http://dx.doi.org/10.4314/ajtcam.v8i5S.9] [PMID: 22754076]
[20]
Shidhaye R, Mendenhall E, Sumathipala K, Sumathipala A, Patel V. Association of somatoform disorders with anxiety and depression in women in low and middle income countries: a systematic review. Int Rev Psychiatry 2013; 25(1): 65-76.
[http://dx.doi.org/10.3109/09540261.2012.748651] [PMID: 23383668]
[21]
Pingali U, Pilli R, Fatima N. Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants. Pharmacognosy Res 2014; 6(1): 12-8.
[http://dx.doi.org/10.4103/0974-8490.122912] [PMID: 24497737]
[22]
Poddighe D, Castelli L, Marseglia GL, Bruni P. A sudden onset of a pseudo-neurological syndrome after HPV-16/18 AS04-adjuvated vaccine: Might it be an autoimmune/inflammatory syndrome induced by adjuvants (ASIA) presenting as a somatoform disorder? Immunol Res 2014; 60(2-3): 236-46.
[http://dx.doi.org/10.1007/s12026-014-8575-3] [PMID: 25388965]
[23]
Jahanbakhsh SP, Manteghi AA, Emami SA, et al. Evaluation of the efficacy of Withania somnifera (Ashwagandha) root extract in patients with obsessive-compulsive disorder: A randomized double-blind placebo-controlled trial. Complement Ther Med 2016; 27: 25-9.
[http://dx.doi.org/10.1016/j.ctim.2016.03.018] [PMID: 27515872]
[24]
Anup BJIMJ. A randomized double blind placebo controlled study of ashwagandha on generalized anxiety disorder. IAMJ 2013; 1(5): 1-7.
[25]
Benjamin J. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. In: Kaplan S 10th ed. Netherland: Wolters Kluwer 2016.
[26]
Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D. Efficacy of treatments for anxiety disorders: A meta-analysis. Int Clin Psychopharmacol 2015; 30(4): 183-92.
[http://dx.doi.org/10.1097/YIC.0000000000000078] [PMID: 25932596]
[27]
Viikki M, Leinonen E. Diagnosis and drug therapy of anxiety disorders in primary health care. Duodecim 2015; 131(6): 583-90.
[PMID: 26237901]
[28]
Singh G, Sharma P, Dudhe R, Singh S. Biological activities of Withania somnifera. Ann Biol Res 2010; 1(3): 56-63.
[29]
Candelario M, Cuellar E, Reyes-Ruiz JM, et al. Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors. J Ethnopharmacol 2015; 171: 264-72.
[http://dx.doi.org/10.1016/j.jep.2015.05.058] [PMID: 26068424]
[30]
Stahl SM. Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications. Cambridge: Cambridge University press 2013.
[31]
Kulkarni SK, Akula KK, Dhir A. Effect of Withania somnifera Dunal root extract against pentylenetetrazol seizure threshold in mice: Possible involvement of GABAergic system. Indian J Exp Biol 2008; 46(6): 465-9.
[PMID: 18697606]
[32]
Pratte MA, Nanavati KB, Young V, Morley CP. An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera). J Altern Complement Med 2014; 20(12): 901-8.
[http://dx.doi.org/10.1089/acm.2014.0177] [PMID: 25405876]
[33]
Mishra L-C, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): A review. Altern Med Rev 2000; 5(4): 334-46.
[PMID: 10956379]
[34]
Gupta GL, Rana AC. Protective effect of Withania somnifera dunal root extract against protracted social isolation induced behavior in rats. Indian J Physiol Pharmacol 2007; 51(4): 345-53.
[PMID: 18476388]
[35]
Archana R, Namasivayam A. Antistressor effect of Withania somnifera. J Ethnopharmacol 1999; 64(1): 91-3.
[http://dx.doi.org/10.1016/S0378-8741(98)00107-X] [PMID: 10075127]
[36]
Gupta GL, Rana AC. Effect of Withania somnifera Dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats. Indian J Exp Biol 2008; 46(6): 470-5.
[PMID: 18697607]
[37]
Verma SK, Kumar A. Therapeutic uses of Withania somnifera (Ashwagandha) with a note on withanolides and its pharmacological actions. Asian J Pharm Clin Res 2011; 4(1): 1-4.
[38]
Bhattacharya SK, Muruganandam AV. Adaptogenic activity of Withania somnifera: An experimental study using a rat model of chronic stress. Pharmacol Biochem Behav 2003; 75(3): 547-55.
[http://dx.doi.org/10.1016/S0091-3057(03)00110-2] [PMID: 12895672]

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