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International guidelines covering the treatment of mixed episodes, manic\/hypomanic, or depressive episodes with mixed features were considered for inclusion. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation\u2010\n                      <jats:styled-content style=\"fixed-case\">AGREE II<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The final selection yielded six articles. Despite their heterogeneity, all guidelines agreed in interrupting an antidepressant monotherapy or adding mood\u2010stabilizing medications. Olanzapine seemed to have the best evidence for acute mixed hypo\/manic\/depressive states and maintenance treatment. Aripiprazole and paliperidone were possible alternatives for acute hypo\/manic mixed states. Lurasidone and ziprasidone were useful in acute mixed depression. Valproate was recommended for the prevention of new mixed episodes while lithium and quetiapine in preventing affective episodes of all polarities. Clozapine and electroconvulsive therapy were effective in refractory mixed episodes. The\n                      <jats:styled-content style=\"fixed-case\">AGREE II<\/jats:styled-content>\n                      overall assessment rate ranged between 42% and 92%, indicating different quality level of included guidelines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acps.12896","type":"journal-article","created":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T00:14:05Z","timestamp":1526256845000},"page":"196-222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Mixed states in bipolar and major depressive disorders: systematic review and quality appraisal of guidelines"],"prefix":"10.1111","volume":"138","author":[{"given":"N.","family":"Verdolini","sequence":"first","affiliation":[{"name":"Bipolar Disorder Unit Institute of Neuroscience Hospital Clinic IDIBAPS CIBERSAM University of Barcelona Barcelona Spain"},{"name":"FIDMAG Germanes Hospital\u00e0ries Research Foundation Sant Boi de Llobregat Barcelona Spain"},{"name":"CIBERSAM Centro Investigaci\u00f3n Biom\u00e9dica en Red Salud Mental Barcelona Spain"},{"name":"Division of Psychiatry, Clinical Psychology and Rehabilitation Department of Medicine Santa Maria della Misericordia Hospital University of Perugia Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Hidalgo\u2010Mazzei","sequence":"additional","affiliation":[{"name":"Bipolar Disorder Unit Institute of Neuroscience Hospital Clinic IDIBAPS CIBERSAM University of Barcelona Barcelona Spain"},{"name":"CIBERSAM Centro Investigaci\u00f3n Biom\u00e9dica en Red Salud Mental Barcelona Spain"},{"name":"Department of Psychological Medicine Centre for Affective Disorders Institute of Psychiatry, Psychology &amp; Neuroscience King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Murru","sequence":"additional","affiliation":[{"name":"Bipolar Disorder Unit Institute of Neuroscience Hospital Clinic IDIBAPS CIBERSAM University of Barcelona Barcelona Spain"},{"name":"CIBERSAM Centro Investigaci\u00f3n Biom\u00e9dica en Red Salud Mental Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Pacchiarotti","sequence":"additional","affiliation":[{"name":"Bipolar Disorder Unit Institute of Neuroscience Hospital Clinic IDIBAPS CIBERSAM University of Barcelona Barcelona Spain"},{"name":"CIBERSAM Centro Investigaci\u00f3n Biom\u00e9dica en Red Salud Mental Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Samalin","sequence":"additional","affiliation":[{"name":"Bipolar Disorder Unit Institute of Neuroscience Hospital Clinic IDIBAPS CIBERSAM University of Barcelona Barcelona Spain"},{"name":"Department of Psychiatry CHU Clermont\u2010Ferrand University of Auvergne Clermont\u2010Ferrand France"},{"name":"Fondation FondaMental P\u00f4le de Psychiatrie H\u00f4pital Albert Chenevier Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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