In　last　decade,　the　US　FDA　has　approved　three　new　antidepressants:　vortioxetine,　levomilnacipran,　and　vilazodone.　Many　studies　have　researched　the　effects　of　these　antidepressants　on　major　depressive　disorder　(MDD),　but　they　have　not　determined　the　optimum　dosage.　This　meta-analysis　investigated　the　efficacies　of　these　three　drugs　at　different　dosages　in　the　treatment　of　MDD.　The　PubMed,　Embase,　Cochrane　Library,　psycINFO,　and　ClinicalTrials.gov　databases　were　searched　to　identify　relevant　literature.　The　primary　outcomes　were　efficacy　(quantified　as　the　change　from　baseline　in　total　score　on　the　Montgomery-Asberg　Depression　Rating　Scale　(MADRS)]　and　tolerability　(discontinuations　due　to　adverse　events).　The　effect　size　was　quantified　as　the　weighted　mean　difference　for　continuous　data　and　the　risk　ratio　(RR)　for　dichotomous　data.　Overall　22　studies　were　included.　The　changes　in　the　MADRS　total　score　were　significantly　higher　for　vortioxetine　at　5,　10,　20,　and　10-20　mg/day　than　for　placebo.　The　tolerability　was　significantly　worse　for　20　mg/day　vortioxetine　than　for　placebo　(RR　=　1.84,　95%　confidence　interval　=　1.13　to　3.02).　In　addition,　increasing　the　dosage　improved　the　efficacy　of　vortioxetine　but　worsened　the　tolerability.　Levomilnacipran　and　vilazodone　at　any　dosage　produced　a　significantly　higher　mean　change　from　baseline　in　the　MADRS　total　score　and　a　worse　tolerability　than　for　placebo.　In　conclusion,　considering　both　efficacy　and　tolerability,　10　mg/day　vortioxetine　might　be　optimal　for　the　treatment　of　MDD.　The　long-term　efficacy　and　safety　of　vortioxetine　needed　to　be　investigated,　and　more　studies　of　levomilnacipran　and　vilazodone　are　needed　to　define　their　optimal　dosages.