{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:21:03Z","timestamp":1788394863726,"version":"build-2803163510"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    : Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders associated with substantial dysfunction and socioeconomic burden. Pharmacotherapy is the first choice for GAD. Remission [Hamilton Anxiety Scale (HAM-A) score \u22647] is regarded as a crucial treatment goal for patients with GAD. There is no up-to-date evidence to compare remission rate and tolerability of all available drugs by using network meta-analysis. Therefore, the goal of our study is to update evidence and determine the best advantageous drugs for GAD in remission rate and tolerability profiles.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Method<\/jats:bold>\n                    : We performed a systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs). We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, wanfang data, China Biology Medicine and\n                    <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                    from their inception to March 2020 to identify eligible double-blind, RCTs reporting the outcome of remission in adult patients who received any pharmacological treatment for GAD. Two reviewers independently assessed quality of included studies utilizing the Cochrane Collaboration\u2019s risk of bias tool as described in Cochrane Collaboration Handbook and extracted data from all manuscripts. Our outcomes were remission rate (proportion of participants with a final score of seven or less on HAM-A) and tolerability (treatments discontinuations due to adverse events). We calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) of each outcome via pairwise and network meta-analysis with random effects.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : Overall, 30 studies were included, comprising 32 double-blind RCTs, involving 13,338 participants diagnosed as GAD by DSM-IV criteria. Twenty-eight trials were rated as moderate risk of bias, four trials as low. For remission rate, agomelatine (OR 2.70, 95% CI 1.74\u20134.19), duloxetine (OR 1.88, 95% CI 1.47\u20132.40), escitalopram (OR 2.03, 95% CI 1.48\u20132.78), paroxetine (OR 1.74, 95% CI 1.25\u20132.42), quetiapine (OR 1.88, 95% CI 1.39\u20132.55), and venlafaxine (OR 2.28, 95% CI 1.69\u20133.07) were superior to placebo. For tolerability, sertraline, agomelatine, vortioxetine, and pregabalin were found to be comparable to placebo. However, the others were worse than placebo in terms of tolerability, with ORs ranging between 1.86 (95% CI 1.25\u20132.75) for tiagabine and 5.98 (95% CI 2.41\u201314.87) for lorazepam. In head-to-head comparisons, agomelatine, duloxetine, escitalopram, quetiapine, and venlafaxine were more efficacious than tiagabine in terms of remission rate, ORs from 1.66 (95% CI 1.04\u20132.65) for duloxetine to 2.38 (95% CI 1.32\u20134.31) for agomelatine. We also found that agomelatine (OR 2.08, 95% CI 1.15\u20133.75) and venlafaxine (OR 1.76, 95% CI 1.08\u20132.86) were superior to vortioxetine. Lorazepam and quetiapine were poorly tolerated when compared with other drugs.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    : Of these interventions, only agomelatine manifested better remission with relatively good tolerability but these results were limited by small sample sizes. Duloxetine, escitalopram, venlafaxine, paroxetine, and quetiapine showed better remission but were poorly tolerated.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2020.580858","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T01:29:01Z","timestamp":1605058141000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":44,"title":["Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials"],"prefix":"10.3389","volume":"11","author":[{"given":"Wenqiang","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyuan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bihui","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1002\/gps.4088","article-title":"Efficacy and safety of duloxetine in the treatment of older adult patients with generalized anxiety disorder: a randomized, double-blind, placebo-controlled trial","volume":"29","author":"Alaka","year":"2014","journal-title":"Int. J. Geriatr. Psychiatr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1176\/appi.ajp.161.9.1642","article-title":"Efficacy of sertraline in a 12-week trial for generalized anxiety disorder","volume":"161","author":"Allgulander","year":"2004","journal-title":"Am. J. Psychiatr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"d1199","DOI":"10.1136\/bmj.d1199","article-title":"Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis","volume":"342","author":"Baldwin","year":"","journal-title":"BMJ"},{"key":"B4","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1017\/s1461145710001434","article-title":"Evidence-based pharmacological treatment of generalized anxiety disorder","volume":"14","author":"Baldwin","year":"2011","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1017\/s1041610215000381","article-title":"Validation of the geriatric anxiety inventory in a duloxetine clinical trial for elderly adults with generalized anxiety disorder","volume":"27","author":"Ball","year":"2015","journal-title":"Int. Psychogeriatr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1017\/s1461145709990423","article-title":"Extended-release quetiapine fumarate (quetiapine xr): a once-daily monotherapy effective in generalized anxiety disorder. Data from a randomized, double-blind, placebo- and active-controlled study","volume":"13","author":"Bandelow","year":"2010","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.euroneuro.2012.07.012","article-title":"Vortioxetine (Lu AA21004) in generalized anxiety disorder: results of an 8-week, multinational, randomized, double-blind, placebo-controlled clinical trial","volume":"22","author":"Bidzan","year":"2012","journal-title":"Eur. Neuropsychopharmacol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1002\/da.20355","article-title":"Randomized placebo-controlled trial of escitalopram and venlafaxine XR in the treatment of generalized anxiety disorder","volume":"2","author":"Bose","year":"2008","journal-title":"Depress. Anxiety"},{"key":"B9","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.eurpsy.2004.05.010","article-title":"Social adjustment in generalised anxiety disorder: a long-term placebo-controlled study of venlafaxine extended release","volume":"19","author":"Boyer","year":"2004","journal-title":"Eur. Psychiatr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1159\/000447034","article-title":"The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature","volume":"85","author":"Carvalho","year":"2016","journal-title":"Psychother. Psychosom."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e76654","DOI":"10.1371\/journal.pone.0076654","article-title":"Graphical tools for network meta-analysis in STATA","volume":"8","author":"Chaimani","year":"2013","journal-title":"PLoS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1002\/jrsm.57","article-title":"Using network meta-analysis to evaluate the existence of small-study effects in a network of interventions","volume":"3","author":"Chaimani","year":"2012","journal-title":"Res. Synth. Methods"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1016\/s0140-6736(17)32802-7","article-title":"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","volume":"391","author":"Cipriani","year":"2018","journal-title":"Lancet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1002\/da.20695","article-title":"Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder","volume":"27","author":"Coric","year":"2010","journal-title":"Depress. Anxiety"},{"key":"B15","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1002\/da.10146","article-title":"Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study","volume":"19","author":"Davidson","year":"2004","journal-title":"Depress. Anxiety"},{"key":"B16","first-page":"40","article-title":"Establishment of remission criteria for anxiety disorders","author":"Doyle","year":"2003","journal-title":"J. Clin. Psychiatr."},{"key":"B17","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1097\/01.jcp.0000084032.22282.ff","article-title":"A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder","volume":"23","author":"Feltner","year":"2003","journal-title":"J. Clin. Psychopharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s40303-015-0011-7","article-title":"A systematic review of agomelatine-induced liver injury","volume":"3","author":"Freiesleben","year":"2015","journal-title":"J. Mol. Psychiatry"},{"key":"B19","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/s0005-7894(97)80048-2","article-title":"Cognitive behavioral and pharmacological treatment of generalized anxiety disorder: a preliminary meta-analysis","volume":"28","author":"Gould","year":"1997","journal-title":"Behav. Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1111\/bph.12720","article-title":"Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties","volume":"171","author":"Guardiola-Lemaitre","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1097\/yic.0b013e32807fb1b2","article-title":"Duloxetine as an SNRI treatment for generalized anxiety disorder: results from a placebo and active-controlled trial","volume":"22","author":"Hartford","year":"2007","journal-title":"Int. Clin. Psychopharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jpsychires.2019.08.009","article-title":"Comparative efficacy and acceptability of first-line drugs for the acute treatment of generalized anxiety disorder in adults: a network meta-analysis","volume":"118","author":"He","year":"2019","journal-title":"J. Psychiatr. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"B24","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1002\/jrsm.1044","article-title":"Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies","volume":"3","author":"Higgins","year":"2012","journal-title":"Res. Synth. Methods"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"777","DOI":"10.7326\/m14-2385","article-title":"The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of Health Care interventions: checklist and explanations","volume":"162","author":"Hutton","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/j.1600-0447.1998.tb05960.x","article-title":"Comorbidity as a fundamental feature of generalized anxiety disorders: results from the national comorbidity study (NCS)","volume":"98","author":"Judd","year":"1998","journal-title":"Acta Psychiatr. Scand."},{"key":"B28","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1017\/s1461145714000017","article-title":"Lavender oil preparation silexan is effective in generalized anxiety disorder\u2013a randomized, double-blind comparison to placebo and paroxetine","volume":"17","author":"Kasper","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1097\/jcp.0b013e318224864d","article-title":"A randomized, double-blind study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalized anxiety disorder","volume":"31","author":"Khan","year":"2011","journal-title":"J. Clin. Psychopharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"100","DOI":"10.4088\/pcc.v09n0203","article-title":"Efficacy of duloxetine for the treatment of generalized anxiety disorder: implications for primary Care physicians","volume":"9","author":"Koponen","year":"2007","journal-title":"Prim. Care Companion J. Clin. Psychiatry"},{"key":"B31","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.phrs.2016.08.017","article-title":"Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: a meta-analysis of observational studies","volume":"118","author":"Laporte","year":"2017","journal-title":"Pharmacol. Res."},{"key":"B32","first-page":"772","article-title":"A double-blind, randomised, placebo controlled study of venlafaxine XL in patients with generalised anxiety disorder in primary Care","volume":"53","author":"Lenox-Smith","year":"2003","journal-title":"Br. J. Gen. Pract."},{"key":"B33","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1111\/dom.12825","article-title":"Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose Co-transporter 2 inhibitors: a meta-analysis of randomized controlled trials","volume":"19","author":"Li","year":"2017","journal-title":"Diabetes Obes. Metabol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1111\/ijcp.12328","article-title":"A randomised, double-blind, placebo-controlled, duloxetine-referenced study of the efficacy and tolerability of vortioxetine in the acute treatment of adults with generalised anxiety disorder","volume":"68","author":"Mahableshwarkar","year":"2014","journal-title":"Int. J. Clin. Pract."},{"key":"B35","first-page":"38","article-title":"Achieving remission in generalized anxiety disorder. What are the treatment options?","volume":"26","author":"Mandos","year":"2009","journal-title":"Psychiatr. Times"},{"key":"B36","doi-asserted-by":"publisher","first-page":"259","DOI":"10.2147\/dddt.s89485","article-title":"Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials","volume":"10","author":"Maneeton","year":"2016","journal-title":"Drug Des. Devel. Ther."},{"key":"B37","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1097\/yic.0b013e32834d9f49","article-title":"Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the acute treatment of generalized anxiety disorder: a randomized, placebo controlled and active-controlled study","volume":"27","author":"Merideth","year":"2012","journal-title":"Int. Clin. Psychopharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1002\/gps.3867","article-title":"Double-blind, randomized study of extended release quetiapine fumarate (quetiapine XR) monotherapy in older patients with generalized anxiety disorder","volume":"28","author":"Mezhebovsky","year":"2013","journal-title":"Int. J. Geriatr. Psychiatr."},{"key":"B39","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1124\/jpet.103.051797","article-title":"The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways","volume":"306","author":"Millan","year":"2003","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B40","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1192\/bjp.bp.107.037788","article-title":"Efficacy and safety of pregabalin in elderly people with generalised anxiety disorder","volume":"193","author":"Montgomery","year":"2008","journal-title":"Br. J. Psychiatry"},{"key":"B41","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1053\/smrv.1999.0096","article-title":"Sleep disturbance in generalized anxiety disorder and its treatment","volume":"4","author":"Monti","year":"2000","journal-title":"Sleep Med. Rev."},{"key":"B42","unstructured":"Generalised anxiety disorder and panic disorder in adults: management2011"},{"key":"B43","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1017\/s0033291708003401","article-title":"Improvement of psychic and somatic symptoms in adult patients with generalized anxiety disorder: examination from a duloxetine, venlafaxine extended-release and placebo-controlled trial","volume":"39","author":"Nicolini","year":"2009","journal-title":"Psychol. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1097\/00004850-200411000-00003","article-title":"Remission rates with venlafaxine extended release in Greek outpatients with generalized anxiety disorder. A double-blind, randomized, placebo controlled study","volume":"19","author":"Nimatoudis","year":"2004","journal-title":"Int. Clin. Psychopharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1016\/j.jpsychires.2008.02.002","article-title":"Early improvement during duloxetine treatment of generalized anxiety disorder predicts response and remission at endpoint","volume":"42","author":"Pollack","year":"","journal-title":"J. Psychiatr. Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1097\/jcp.0b013e318172b45f","article-title":"Tiagabine in adult patients with generalized anxiety disorder: results from 3 randomized, double-blind, placebo-controlled, parallel-group studies","volume":"28","author":"Pollack","year":"","journal-title":"J. Clin. Psychopharmacol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"350","DOI":"10.4088\/jcp.v62n0508","article-title":"Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial","volume":"62","author":"Pollack","year":"2001","journal-title":"J. Clin. Psychiatr."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e033161","DOI":"10.1136\/bmjopen-2019-033161","article-title":"Vortioxetine treatment for generalised anxiety disorder: a meta-analysis of anxiety, quality of life and safety outcomes","volume":"9","author":"Qin","year":"2019","journal-title":"BMJ Open"},{"key":"B49","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1176\/appi.ajp.160.4.749","article-title":"Paroxetine treatment of generalized anxiety disorder: a double-blind, placebo-controlled study","volume":"160","author":"Rickels","year":"2003","journal-title":"Am. J. Psychiatry"},{"key":"B50","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.euroneuro.2012.07.011","article-title":"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","volume":"22","author":"Rothschild","year":"2012","journal-title":"Eur. Neuropsychopharmacol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1002\/da.20271","article-title":"Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial","volume":"25","author":"Rynn","year":"2008","journal-title":"Depress. Anxiety"},{"key":"B52","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jclinepi.2010.03.016","article-title":"Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial","volume":"64","author":"Salanti","year":"2011","journal-title":"J. Clin. Epidemiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/s0140-6736(18)31793-8","article-title":"Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis","volume":"393","author":"Slee","year":"2019","journal-title":"Lancet"},{"key":"B54","doi-asserted-by":"publisher","first-page":"285","DOI":"10.7326\/0003-4819-159-4-201308200-00009","article-title":"Handling of rescue and missing data affects synthesis and interpretation of evidence: the sodium-glucose cotransporter 2 inhibitor example","volume":"159","author":"Stack","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1097\/jcp.0b013e318184ff5b","article-title":"Efficacy of agomelatine in generalized anxiety disorder: a randomized, double-blind, placebo-controlled study","volume":"28","author":"Stein","year":"2008","journal-title":"J. Clin. Psychopharmacol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1002\/hup.1256","article-title":"Efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalised anxiety disorder: an analysis of pooled data from three 8-week placebo-controlled studies","volume":"26","author":"Stein","year":"2011","journal-title":"Hum. Psychopharmacol. Clin. Exp."},{"key":"B57","doi-asserted-by":"publisher","first-page":"362","DOI":"10.4088\/jcp.13m08433","article-title":"Agomelatine in generalized anxiety disorder: an active comparator and placebo-controlled study","volume":"75","author":"Stein","year":"2014","journal-title":"J. Clin. Psychiatr."},{"key":"B58","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.euroneuro.2017.02.007","article-title":"Efficacy and safety of agomelatine (10 or 25 Mg\/day) in non-depressed out-patients with generalized anxiety disorder: a 12-week, double-blind, placebo-controlled study","volume":"27","author":"Stein","year":"2017","journal-title":"Eur. Neuropsychopharmacol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1016\/s0140-6736(06)69865-6","article-title":"Generalised anxiety disorder","volume":"368","author":"Tyrer","year":"2006","journal-title":"Lancet"},{"key":"B60","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.euroneuro.2005.04.012","article-title":"Size and burden of mental disorders in europe\u2013a critical review and appraisal of 27 studies","volume":"15","author":"Wittchen","year":"2005","journal-title":"Eur. Neuropsychopharmacol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"3260","DOI":"10.3760\/cma.j.issn.0366-6999.2011.20.010","article-title":"Duloxetine versus placebo in the treatment of patients with generalized anxiety disorder in China","volume":"124","author":"Wu","year":"2011","journal-title":"Chin. Med. J."},{"key":"B62","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jad.2018.02.012","article-title":"Generalized anxiety disorder in urban China: prevalence, awareness, and disease burden","volume":"234","author":"Yu","year":"2018","journal-title":"J. Affect. Disord."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2020.580858\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T11:43:52Z","timestamp":1606909432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2020.580858\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,11]]},"references-count":62,"alternative-id":["10.3389\/fphar.2020.580858"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2020.580858","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,11]]},"article-number":"580858"}}