{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T17:29:21Z","timestamp":1774459761119,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T00:00:00Z","timestamp":1455580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Evidence supporting the use of second generation antipsychotics (SGAs) in the treatment of acute depression with mixed features (MFs) associated with bipolar disorder (BD) is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo-) controlled trials (RCTs) or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD) between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI). Six RCTs and one open-label placebo-controlled studies (including post-hoc reports) representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-)manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS) (SMD \u22120.74, 95% CI \u22121.20 to \u22120.28, n SGA = 907, control = 652). Meta-analysis demonstrated that participants in receipt of SGA (n = 979) experienced a large improvement in the Montgomery\u2013\u00c5sberg Depression Rating Scale (MADRS) scores (SMD \u22121.08, 95% CI \u22121.35 to \u22120.81, p &lt; 0.001) vs. placebo (n = 678). Publication and measurement biases and relative paucity of studies. Overall, SGAs appear to offer favorable improvements in MADRS and YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable and clinically definitive conclusions.<\/jats:p>","DOI":"10.3390\/ijms17020241","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T10:39:15Z","timestamp":1455619155000},"page":"241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Atypical Antipsychotics in the Treatment of Acute Bipolar Depression with Mixed Features: A Systematic Review and Exploratory Meta-Analysis of Placebo-Controlled Clinical Trials"],"prefix":"10.3390","volume":"17","author":[{"given":"Michele","family":"Fornaro","sequence":"first","affiliation":[{"name":"New York Psychiatric Institute, Columbia University, New York City, NY 10032, USA"}]},{"given":"Brendon","family":"Stubbs","sequence":"additional","affiliation":[{"name":"Health Service and Population Research Department, Institute of Psychiatry, King\u2019s College London, De Crespigny Park, London SE5 8AF, UK"},{"name":"Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4415-5058","authenticated-orcid":false,"given":"Domenico","family":"De Berardis","sequence":"additional","affiliation":[{"name":"National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital. Mazzini, ASL 4, Teramo 64100, Italy"}]},{"given":"Giampaolo","family":"Perna","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Hermanas Hospitalarias\u2014Villa San Benedetto Menni Hospital, FoRiPsi 22032, Italy"}]},{"given":"Alessandro","family":"Valchera","sequence":"additional","affiliation":[{"name":"Hermanas Hospitalarias\u2014Villa San Giuseppe, Ascoli Piceno 63100, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9328-289X","authenticated-orcid":false,"given":"Nicola","family":"Veronese","sequence":"additional","affiliation":[{"name":"Department of Medicine (DIMED), University of Padua, Padova 35121, Italy"}]},{"given":"Marco","family":"Solmi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of Padua, Padova 35121, Italy"}]},{"given":"Lic\u00ednia","family":"Ganan\u00e7a","sequence":"additional","affiliation":[{"name":"New York Psychiatric Institute, Columbia University, New York City, NY 10032, USA"},{"name":"Departamento de Psiquiatria e Sa\u00fade Mental, Faculdade de Medicina, Universidade de Lisboa, Lisbon 1649-035, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hayes, J., Prah, P., Nazareth, I., King, M., Walters, K., Petersen, I., and Osborn, D. (2011). Prescribing trends in bipolar disorder: Cohort study in the United Kingdom THIN primary care database 1995\u20132009. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028725"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1192\/bjp.bp.110.083766","article-title":"The rise and fall of the atypical antipsychotics","volume":"199","author":"Kendall","year":"2011","journal-title":"Br. J. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jad.2013.10.054","article-title":"Trends in pharmacotherapy in patients referred to a bipolar specialty clinic, 2000\u20132011","volume":"155","author":"Hooshmand","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jad.2015.04.032","article-title":"Mortality and secular trend in the incidence of bipolar disorder","volume":"183","author":"Medici","year":"2015","journal-title":"J. Affect. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bauer, M., Glenn, T., Alda, M., Sagduyu, K., Marsh, W., Grof, P., Munoz, R., Severus, E., Ritter, P., and Whybrow, P.C. (2013). Drug treatment patterns in bipolar disorder: Analysis of long-term self-reported data. Int. J. Bipolar Disord., 1.","DOI":"10.1186\/2194-7511-1-5"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/bdi.12234","article-title":"Population study of disease burden, management, and treatment of bipolar disorder in Sweden: A retrospective observational registry study","volume":"17","author":"Carlborg","year":"2015","journal-title":"Bipolar Disord."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Stubbs, B., Vancampfort, D., Solmi, M., Veronese, N., and Fornaro, M. (2016). How common is bipolar disorder in general primary care attendees? A systematic review and meta-analysis investigating prevalence determined according to structured clinical assessments. Aust. N. Z. J. Psychiatry.","DOI":"10.1177\/0004867415623857"},{"key":"ref_8","first-page":"215","article-title":"\u201cBipolar missed states\u201d: The diagnosis and clinical salience of bipolar mixed states","volume":"39","author":"Berk","year":"2005","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_9","unstructured":"American Psychiatric Association (APA) (1994). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [4th ed.]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1176\/appi.ajp.2008.08050746","article-title":"Manic symptoms during depressive episodes in 1380 patients with bipolar disorder: Findings from the STEP-BD","volume":"166","author":"Goldberg","year":"2009","journal-title":"Am. J. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (APA) (2013). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_12","first-page":"259","article-title":"The prevalence and illness characteristics of DSM-5-defined \u2018mixed feature specifier\u2019 in adults with major depressive disorder and bipolar disorder: Results from the International Mood Disorders Collaborative Project","volume":"172C","author":"McIntyre","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e351","DOI":"10.4088\/JCP.14m09092","article-title":"Mixed features in patients with a major depressive episode: The BRIDGE-II-MIX study","volume":"76","author":"Perugi","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jad.2014.04.003","article-title":"Efficacy of olanzapine monotherapy in the treatment of bipolar depression with mixed features","volume":"164","author":"Tohen","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e378","DOI":"10.4088\/JCP.14com09578","article-title":"Mixed depression: A farewell to differential diagnosis?","volume":"76","author":"Goldberg","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hu, J., Mansur, R., and McIntyre, R.S. (2014). Mixed specifier for bipolar mania and depression: Highlights of DSM-5 changes and implications for diagnosis and treatment in primary care. Prim Care Companion CNS Disord., 16.","DOI":"10.4088\/PCC.13r01599"},{"key":"ref_17","first-page":"114","article-title":"Exploratory factor analysis of mixed depression utilizing a modified version of Hypomania Checklist 32 (mHCL-32)","volume":"15","author":"Prieto","year":"2013","journal-title":"Bipolar Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1192\/bjp.bp.112.124404","article-title":"Mixed features of depression: Why DSM-5 is wrong (and so was DSM-IV)","volume":"203","author":"Koukopoulos","year":"2013","journal-title":"Br. J. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jad.2014.03.054","article-title":"Koukopoulos\u2019 diagnostic criteria for mixed depression: A validation study","volume":"164","author":"Sani","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.jad.2011.12.046","article-title":"Prevalence and clinical significance of subsyndromal manic symptoms, including irritability and psychomotor agitation, during bipolar major depressive episodes","volume":"138","author":"Judd","year":"2012","journal-title":"J. Affect. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S0140-6736(07)60453-X","article-title":"Bipolar disorder\u2014Focus on bipolar II disorder and mixed depression","volume":"369","author":"Benazzi","year":"2007","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.pnpbp.2007.08.005","article-title":"A tetrachoric factor analysis validation of mixed depression","volume":"32","author":"Benazzi","year":"2008","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Swann, A.C. (2013). Activated depression: Mixed bipolar disorder or agitated unipolar depression?. Curr. Psychiatry Rep., 15.","DOI":"10.1007\/s11920-013-0376-1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/pcn.12213","article-title":"DSM-5-defined \u2018mixed features\u2019 and Benazzi\u2019s mixed depression: Which is practically useful to discriminate bipolar disorder from unipolar depression in patients with depression?","volume":"69","author":"Takeshima","year":"2015","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1177\/0004867415585858","article-title":"Agitation for recognition by DSM-5 mixed features specifier signals fatigue?","volume":"49","author":"Malhi","year":"2015","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1399-5618.2007.00557.x","article-title":"All mixed up: On the absence of diagnostic guidelines for mixed states in the ISBD Diagnostic Guidelines Task Force Report","volume":"10","author":"Ghaemi","year":"2008","journal-title":"Bipolar Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1517\/14656566.2011.632366","article-title":"Could the underestimation of bipolarity obstruct the search for novel antidepressant drugs?","volume":"12","author":"Fornaro","year":"2011","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/da.22378","article-title":"The American society of clinical psychopharmacology survey of psychopharmacologists\u2019 practice patterns for the treatment of mood disorders","volume":"32","author":"Goldberg","year":"2015","journal-title":"Depress Anxiety"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"398","DOI":"10.4088\/JCP.14m09410","article-title":"Lurasidone in the treatment of bipolar depression with mixed (subsyndromal hypomanic) features: Post hoc analysis of a randomized placebo-controlled trial","volume":"76","author":"McIntyre","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1111\/acer.12445","article-title":"A randomized, double-blind, placebo-controlled trial of quetiapine in patients with bipolar disorder, mixed or depressed phase, and alcohol dependence","volume":"38","author":"Davila","year":"2014","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"728","DOI":"10.4088\/JCP.13m08827","article-title":"Effects of asenapine in bipolar I patients meeting proxy criteria for moderate-to-severe mixed major depressive episodes: A post hoc analysis","volume":"76","author":"Berk","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.4088\/JCP.08m04772gre","article-title":"Olanzapine\/fluoxetine combination for the treatment of mixed depression in bipolar I disorder: A post hoc analysis","volume":"70","author":"Benazzi","year":"2009","journal-title":"J. Clin. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Patkar, A., Gilmer, W., Pae, C.U., Vohringer, P.A., Ziffra, M., Pirok, E., Mulligan, M., Filkowski, M.M., Whitham, E.A., and Holtzman, N.S. (2012). A 6 week randomized double-blind placebo-controlled trial of ziprasidone for the acute depressive mixed state. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034757"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1055\/s-0031-1297984","article-title":"Predictors of response to ziprasidone: Results from a 6-week randomized double-blind, placebo-controlled trial for acute depressive mixed state","volume":"45","author":"Pae","year":"2012","journal-title":"Pharmacopsychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/S0197-2456(99)00026-4","article-title":"Assessing the quality of randomized trials: Reliability of the Jadad scale","volume":"20","author":"Clark","year":"1999","journal-title":"Controll. Clin. Trials"},{"key":"ref_36","unstructured":"Wells, G., Shea, B., O\u2019connell, D., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2000). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses, Ottawa Hospital Research Institute."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1192\/bjp.134.4.382","article-title":"A new depression scale designed to be sensitive to change","volume":"134","author":"Montgomery","year":"1979","journal-title":"Br. J. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1192\/bjp.133.5.429","article-title":"A rating scale for mania: Reliability, validity and sensitivity","volume":"133","author":"Young","year":"1978","journal-title":"Br. J. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jad.2008.01.004","article-title":"A prospective, open-label study of Aripiprazole mono- and adjunctive treatment in acute bipolar depression","volume":"110","author":"Dunn","year":"2008","journal-title":"J. Affect. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jad.2015.12.009","article-title":"Are manic symptoms that \u2018dip\u2019 into depression the essence of mixed features?","volume":"192","author":"Malhi","year":"2016","journal-title":"J. Affect. Disord."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"256","DOI":"10.2174\/15748847113089990056","article-title":"Efficacy and safety of long acting injectable atypical antipsychotics: A review","volume":"8","author":"Marini","year":"2013","journal-title":"Curr. Clin. Pharmacol."},{"key":"#cr-split#-ref_42.1","doi-asserted-by":"crossref","unstructured":"Fornaro, M., de Berardis, D., Iasevoli, F., Pistorio, M.L., D'Angelo, E., Mungo, S., Martino, M., Ventriglio, A., Cattaneo, C.I., and Favaretto, E. (2014). Corrigendum to 'Treatment adherence towards prescribed medications in bipolar-II acute depressed patients: Relationship with cyclothymic temperament and 'therapeutic sensation seeking' in response towards subjective intolerance to pain' [J. Affect. Disord. 151","DOI":"10.1016\/j.jad.2013.07.004"},{"key":"#cr-split#-ref_42.2","unstructured":"(2) (November 2013), 596-604]. J. Affect. Disord., 170C."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fornaro, M., De Berardis, D., Koshy, A.N., Perna, G., Valchera, A., Vancampfort, D., and Stubbs, B. (2016). Prevalence and clinical features associated with bipolar disorder polypharmacy: A systematic review. Neuropsychiatr. Dis. Treat., in press.","DOI":"10.2147\/NDT.S100846"},{"key":"ref_44","first-page":"261","article-title":"Bipolar disorder treatment guidelines and their limits in every day clinical practice","volume":"17","author":"Perugi","year":"2011","journal-title":"G. Ital. Psicopatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20","DOI":"10.2174\/1745017901006010020","article-title":"Current nosology of treatment resistant depression: A controversy resistant to revision","volume":"6","author":"Fornaro","year":"2010","journal-title":"Clin. Pract. Epidemiol. Ment. Health"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Marneros, A., and Goodwin, F. (2005). Bipolar Disorders: Mixed States, Rapid Cycling and Atypical Forms, Cambridge University Press.","DOI":"10.1017\/CBO9780511544019"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e381","DOI":"10.4088\/JCP.14com09487","article-title":"\u201cMixed\u201d depression: Drawbacks of DSM-5 (and other) polythetic diagnostic criteria","volume":"76","author":"Maj","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/acps.12140","article-title":"DSM-5 criteria for depression with mixed features: A farewell to mixed depression","volume":"129","author":"Koukopoulos","year":"2014","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Suppes, T., Silva, R., Cucchiaro, J., Mao, Y., Targum, S., Streicher, C., Pikalov, A., and Loebel, A. (2015). Lurasidone for the Treatment of Major Depressive Disorder With Mixed Features: A Randomized, Double-Blind, Placebo-Controlled Study. Am. J. Psychiatry.","DOI":"10.1176\/appi.ajp.2015.15060770"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1517\/14656566.2012.719877","article-title":"The argument of antidepressant drugs in the treatment of bipolar depression: Mixed evidence or mixed states?","volume":"13","author":"Fornaro","year":"2012","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Roberts, R.J., Lohano, K.K., and El-Mallakh, R.S. (2015). Antipsychotics as antidepressants. Asia Pac. Psychiatry.","DOI":"10.1111\/appy.12186"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Davey, J., Turner, R.M., Clarke, M.J., and Higgins, J.P. (2011). Characteristics of meta-analyses and their component studies in the Cochrane Database of Systematic Reviews: A cross-sectional, descriptive analysis. BMC Med. Res. Methodol., 11.","DOI":"10.1186\/1471-2288-11-160"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1002\/sim.6525","article-title":"Publication bias in meta-analyses from the Cochrane Database of Systematic Reviews","volume":"34","author":"Kicinski","year":"2015","journal-title":"Stat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1001\/jama.283.15.2008","article-title":"Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group","volume":"283","author":"Stroup","year":"2000","journal-title":"JAMA"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Qi, X., Yang, M., Ren, W., Jia, J., Wang, J., Han, G., and Fan, D. (2013). Find duplicates among the PubMed, EMBASE, and Cochrane Library Databases in systematic review. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071838"},{"key":"ref_56","unstructured":"Reuters, T. (2013). Endnote X7, Thomson Reuters."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","article-title":"A rating scale for depression","volume":"23","author":"Hamilton","year":"1960","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.euroneuro.2006.04.008","article-title":"The Montgomery Asberg and the Hamilton ratings of depression: A comparison of measures","volume":"16","author":"Carmody","year":"2006","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_59","unstructured":"Borenstein, M., Hedges, L., Higgins, J., and Rothstein, H. (2005). Comprehensive Meta-Analysis Version 3, Biostat."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Higgins, J.P., Altman, D.G., Gotzsche, P.C., Juni, P., Moher, D., Oxman, A.D., Savovic, J., Schulz, K.F., Weeks, L., and Sterne, J.A. (2011). The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials. BMJ, 343.","DOI":"10.1136\/bmj.d5928"},{"key":"ref_61","unstructured":"Taylor, S., and Tweedie, R. (1998). A Non-Parametric \u2018Trim and Fill\u2019 Method of Assessing Publication Bias in Meta-Analysis, University of Colorado Health Sciences Center."},{"key":"ref_62","first-page":"12","article-title":"The DSM-V: Simplify, clarify","volume":"2","author":"Roth","year":"2005","journal-title":"Psychiatry"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/2\/241\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:19:12Z","timestamp":1760210352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/2\/241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,16]]},"references-count":63,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,2]]}},"alternative-id":["ijms17020241"],"URL":"https:\/\/doi.org\/10.3390\/ijms17020241","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,16]]}}}