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["Author, year\nCountry\nNCT number\nOther trial Identifier\nOverall quality","Source of data","Comparisons","Eligibility","Exclusion","Total randomized\nRandomized/Treated per arm","Basline\nAge\nSex\nRace","Baseline\nHAMD\nHAMA\nMADRS","Duration of follow-up","Efficacy Outcomes (FAS, LOCF)\nResponse\nRemission","Efficacy Outcomes\nChange (standard error) from baseline \nMADRS or HAMD","Adverse events","Funding source","Quality"]
["Alvarez et al, 2011\nEurope, Australia, Canada\n\nNCT00839423\n\n11492A\n\n","published","V5: Vortioxetine 5 mg\nV10: vortioxetine 10mg\nP: placebo\nVEN: venlafaxine XR 225mg","Patients with MDD presenting with current major depressive episode of at least 3 months according to DSM-IV-TR criteria; outpatient; 18-65 years old; MADRS total score ≥30  at baseline visit ","Current psychiatric disorder other than MDD (assessed using MINI), or if current or past history of manic or hypomanic episode, schipohrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition, any substance abuse disorder within the previous 6 months, presence or history of a clinically significant neurological disorder (including epilepsy), any neurodegenerative disorder, or any Axis II disorder that might compromise the study.\n\nPatients at serious risk of suicide or who had score of ≥ 5 on item 10 of MADRS scale, those receiving formal behaviour therapy or systematic psychotherapy, who were pregnant or breastfeeding, who had a known hypersensitivity or were non-response to venlafaxine, or whose current depressive symptoms were considered by the investigator to have been reisitant to two adequate antidepressant treatments of at least 6 week duration, or had previously been exposed to Lu AA21004\n\nPatients who took psychotropic drugs within 2 weeks prior to baseline or during the study.","n=429\n\nV5: 109 / 108\nV10: 101 /100\nP: 105 / 105\nVEN: 114 / 113","V5 vs V10 vs P vs VEN\n\nAge:   43.8  ± 11.6 vs  42.3  ± 13.1 vs 42.0  ± 10.9 vs 45.0  ± 10.3  \nFemale: 64.8% vs 66% vs 65.7% vs 54.9%\nNon-white: 6.5% vs 11.0% vs 6.7% vs 8.0%","V5 vs V10 vs P vs VEN\n\nHAMD24: 22.9 vs. 29.3 vs. 29.7 vs. 29.4\nHAMA: 21.7 vs. 22.3 vs. 22.9 vs. 22.0\nMADRS: 34.1 vs. 34.0 vs. 33.9 vs. 34.2","6 weeks","V5 vs V10 vs P vs VEN\n\nResponse\nMADRS: 72/108 (66.7%) vs. 68/100 (68.0%) vs. 47/105 (44.8%) vs. 81/112 (72.3%) \nHAMD24: 78/108 (72.2%) vs. 69/100 (69.0%) vs. 42/105 (40.0%) vs. 81/112 (72.3%) \n\nRemission\nMADRS: 53/108 (49.1%) vs. 49/100 (49.0%) vs. 28/105 (26.7%) vs. 62/112 (55.4%) \nHAMD17: 51/108 (47.2%) vs. 45/100 (45.0%) vs. 29/105 (27.6%) vs. 52/112 (46.4%) \n","V5 vs V10 vs P vs VEN\n\nMADRS*:  -20.4 (1.0) vs. -20.2 (1.0) vs.  -14.5 (1.0) vs. -20.9 (1.0)\n\n\n","V5 vs V10 vs P vs VEN\n\nWithdrawals due to adverse events: 3/108 (2.8%) vs. 7/100 (7.0%) vs. 4/105 (3.8%) vs. 16/113 (14.3%) \nSerious adverse event: 0/108 (0%) vs. 2/100 (2%) vs. 0/105 (0%) vs. 1/113 (<1%) \nDeaths: None\n\nSpecific Adverse Events\nNausea: 32/108 (29.6%) vs. 38/100 (38.0%) vs. 10/105 (9.5%) vs. 38 /113(33.6%)\nVomiting:  2/108 (1.9%) vs 9/100 (9.0%) vs 1/105 (1.0%) vs 4/113 (3.5%)\nHeadache: 23/108 (21.3%) vs. 25/100 (25.0%) vs. 26/105 (24.8%) vs. 32/113 (28.3%)\nDiarrhea: 9/108 (8.3%) vs. 7/100 (7.0%) vs. 5/105 (4.8%) vs. 5/113 (4.4%)\nDizziness: 7/108 (6.5%) vs. 7/100 (7.0%) vs. 8/105 (7.6%) vs. 14/113 (12.4%)\nDry mouth: 8/108 (7.4%) vs. 8/100 (8.0%) vs. 7/105 (6.7%) vs. 19/113 (16.8%)\nHyperhydrosis:  3/108 (2.8%) vs 10/100 (10.0%) vs 2/105 (1.9%) vs 17/113 (15.0%)\nNasopharyngitis: 8/108 (7.4%) vs. 7/100 (7.0%) vs. 9/105 (8.6%) vs. 4/113 (3.5%)\nInsomnia: 7/108 (6.5%) vs. 6/100 (6.0%) vs. 5 /105 (4.8%) vs. 14/113 (12.4%)\nFatigue:  4/108 (3.7%) vs 6/100 (6.0%) vs 6/105 (5.7%) vs 11/113 (9.7%)\n","H. Lundbeck A/S","Randomization: Yes\nAllocation concealment: Yes\nSimilar groups at baseline: Yes\nEligibility criteria specified: Yes\nOutcome assessors masked: Yes\nCare providers masked: Yes\nPatients masked: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: No\nIntention-to-treat: Yes\nOverall rating: Good"]
["Mahableshwarkar et al, 2013\nUS\n\nNCT00672620\n\n304\n","published","V2.5: vortioxetine 2.5 mg\nV5: vortioxetine 5 mg\nP: placebo \nD: duloxetine 60 mg","Patients with MDD presenting with current major depressive episode according to DSM-IV-TR criteria; outpatient; 18-75 years old; MADRS total score ≥ 22 at baseline visit ","Current psychiatric disorder other than MDD (assessed using MINI), or if current or past history of manic or hypomanic episode, schipohrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition, any substance abuse disorder within the previous 6 months, presence or history of a clinically significant neurological disorder (including epilepsy), any neurodegenerative disorder, or any Axis II disorder that might compromise the study.\n\nPatients at serious risk of suicide or who had score of ≥ 5 on item 10 of MADRS scale, those receiving formal behaviour therapy or systematic psychotherapy, who were pregnant or breastfeeding, who had a known hypersensitivity or were non-response to venlafaxine, or whose current depressive symptoms were considered by the investigator to have been reisitant to two adequate antidepressant treatments of at least 6 week duration, or had recieved electroconvulsive therapy in preceeding 6 months","n=611\n\nV2.5: 153 / 149\nV5: 153 / 153\nP: 153 / 151 \nD: 152 / 150\n","V2.5 vs V5 vs P vs D\n\nAge: 42.6  ± 12.85 vs 43.1  ± 13.89 vs 42.6  ± 13.76 vs 42.7  ± 14.38  \nFemale: 64.0% vs 69.3% vs 60.8% vs 59.9%\nNon-white: 26.8% vs 29.4% vs 20.9% vs 27.0%","V2.5 vs V5 vs P vs D\n\nHAMD24: 29.8 vs. 29.8 vs. 29.5 vs. 28.7\nHAMA: 19.3 vs. 18.7 vs. 18.8 vs. 17.4\nMADRS: 29.8 vs. 30.1 vs. 30.0 vs. 29.4","8 weeks","V2.5 vs V5 vs P vs D\n\nResponse\nHAMD24: 60/146 (41.1%) vs. 58/153 (37.9%) vs. 48/149 (32.2%) vs. 76/149 (51.0%) \n\nRemission\nMADRS: 33/146 (22.6%) vs. 32/153 (20.9%) vs. 33/149 (22.1%) vs. 51/149 (34.2%) \n","V2.5 vs V5 vs P vs D\n\nMADRS*: -11.6 (0.8) vs. 11.3 (0.8) vs. -11.2 (0.8) vs. -14.1 (0.8)\n\nHAMD24:  -12.04 ( 0.8) vs. -11.05 (0.7) vs. -10.5 (0.8) vs. -13.47 (0.8)\n\n","V2.5 vs V5 vs P vs D\n\nWithdrawals due to adverse events:  7/149 (4.7%) vs. 12/153 (7.8%) vs. 7/151 (4.6%) vs. 17/150 (11.3%)\nSerious adverse event: 0/153 (0%) vs. 4/153 (2.6%) vs. 2/153 (1.3%) vs. 2/152 (1.3%)\nDeaths: None\n\nSpecific Adverse Events\nNausea: 24/149 (16.1%) vs. 44/153 (28.8%) vs. 16/151 (10.6) vs. 63/150 (42.0%)\nVomiting:  1/149 (0.7%) vs 7/153 (4.6%) vs 1/151 (0.7%) vs 5/150 (3.3%)\nHeadache: 20/149 (13.4%) vs. 24/153 (15.7%) vs. 18/151 (11.9%) vs. 21/150 (14.0%)\nDiarrhea: 7/149 (4.7%) vs. 14/153 (9.2%) vs. 13/151 (8.6%) vs. 19/150 (12.7%)\nDizziness: 10/149 (6.7%) vs. 9/153 (5.9%) vs. 7/151 (4.6%) vs. 22/150 (14.7%)\nDry mouth: 16/149 (10.7%) vs. 16/153 (10.5%) vs. 11/151 (7.3%) vs. 40/150 (26.7%)\nHyperhydrosis: 4/149 (2.7%) vs 4/153 (2.6%) vs 4/151 (2.6%) vs 11/150 (7.3%)\nNasopharyngitis:  not reported\nInsomnia: 6/149 (4.0%) vs. 6/153 (3.9%) vs. 6/151 (4.0%) vs. 11/150 (7.3%)\nFatigue: 3/149 (2.0%) vs 3/153 (2.0%) vs 5/151 (3.3%) vs 13/150 (8.7%)\n","Takeda Pharmaceutical company","Randomization: Yes\nAllocation concealment: Yes\nSimilar groups at baseline: Yes\nEligibility criteria specified: Yes\nOutcome assessors masked: Unclear\nCare providers masked: Yes\nPatients masked: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: Yes\nIntention-to-treat: Yes\nOverall rating: Fair"]
["Baldwin et al, 2012\nEurope, Canada, Australia, Asia\n\nNCT00635219\n\n11984A","published","V2.5: vortioxetine 2.5 mg\nV5: vortioxetine 5 mg\nV10: vortioxetine 10 mg\nP: placebo\nD: duloxetine 60 mg","Patients with MDD presenting with current major depressive episode according to DSM-IV-TR criteria; outpatient; 18-75 years old; MADRS total score ≥ 26 at baseline visit ","Current psychiatric disorder other than MDD (assessed using MINI), or if current or past history of manic or hypomanic episode, schipohrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition, any substance abuse disorder within the previous 6 months, presence or history of a clinically significant neurological disorder (including epilepsy), any neurodegenerative disorder, or any Axis II disorder that might compromise the study.\n\nPatients at serious risk of suicide or who had score of ≥ 5 on item 10 of MADRS scale, those receiving formal behaviour therapy or systematic psychotherapy, who were pregnant or breastfeeding, or whose current depressive symptoms were considered by the investigator to have been reisitant to two adequate antidepressant treatments of at least 6 week duration, or had previously been exposed to Lu AA21004\n\nPatients who took psychotropic drugs within 2 weeks prior to baseline or during the study. Patients were withdrawn from the study if they became preganant, became suicidal or did not take their medicine for >6 days","n=776\n\nV2.5:  155 / 155\nV5:  159 / 157\nV10:  153 / 151\nP:  152 / 148\nD:  157 / 155\n\n","V2.5 vs V5 vs V10 vs P vs D\n\nAge:  46 ± 12.5 vs 44.7 ±  13.1 vs 45.2 ±  13.1 vs 43.4 ±  12.5 vs 45.3 ± 12.0\nFemale: 71.0% vs 66.2% vs 68.1% vs 69.6% vs 67.7%\nNon-white:  22.6% vs 22.3% vs 23.2% vs 22.3% vs 21.9%","V2.5 vs V5 vs V10 vs P vs D\n\nHAMD24: 29.6 vs. 31.3 vs. 30.4 vs. 29.8 vs. 29.9\nHAMA: 22.2 vs. 23.5 vs. 23.4 vs. 23.1 vs. 22.8\nMADRS: 31.6 vs. 32.7 vs. 31.8 vs. 31.7 vs. 31.4\nHAMD17: 22.7 vs. 24.1 vs. 23.4 vs. 23.1 vs. 23.2","8 weeks","V2.5 vs V5 vs V10 vs P vs D\n\nResponse\nMADRS: 84/155 (54.2%) vs 87/155 (56.1%) vs 88/151 (58.3%)  vs 68/145 (46.9%) vs 85/149 (57.0%)\n\nRemission\nMADRS: 51/155 (32.9%) vs 56/155 (36.1%) vs 54/151 (35.8%) vs 49/145 (33.8%) vs 52/149 (54.1%)\nHAMD: 47/155 (30.3%) vs 57/155 (36.8%) vs 57/151 (37.7%) vs NR vs 51/149 (34.2%)\n\n","V2.5 vs V5 vs V10 vs P vs D\n\nMADRS:  -16.2 (0.8) vs. -16.5 (0.8) vs.  -16.3 (0.8) vs. -14.8 (0.8) vs. -16.8 (0.8)\n\nHAMD24*:  -14.4 (0.8) vs. -15 (0.8) vs. -14.9 (0.80) vs. -13.3 (0.8) vs. -15.7 (0.8)\n","V2.5 vs V5 vs V10 vs P vs D \n\nWithdrawals due to adverse events:  10/155 (6.5%) vs. 18/157 (11.5%) vs. 15/151 (9.9%) vs. 12/148 (8.1%) vs. 19/155(12.3%)\nSerious adverse event*:  1/155 (0.7%) vs 3/157 (1.9%) vs 2/151 (1.3%) vs 3/148 (2.0%) vs 2/155 (1.3%)\nDeaths: 1 (V5)\n\nSpecific Adverse Events\nNausea: 26/155 (16.8%) vs. 26/157 (16.6%) vs. 33/151 (21.9%) vs. 13/148 (8.8%) vs. 52/155 (33.5%)\nVomiting:  6/155 (3.9%) vs 6/157 (3.8%) vs 7/151 (4.6%) vs 5/148 (3.4%) vs 11/155 (7.1%) \nHeadache: 22/155 (14.2%) vs. 16/157 (10.2%) vs. 19/151 (12.6%) vs. 24/148 (16.2%) vs. 22/155 (14.2%)\nDiarrhea: 7/155 (4.5%) vs. 3/157 (1.9) vs. 8/151 (5.3%) vs. 10/148 (6.8%) vs. 7/155 (4.5%)\nDizziness: 7/155 (4.5%) vs. 5/157 (3.2%) vs. 6/151 (4.0%) vs. 10148 (6.8%) vs. 25/155 (16.1%)\nDry mouth: 6/155 (3.9%) vs. 9/157 (5.7%) vs. 6/151 (4.0%) vs. 11/148 (7.4%) vs. 12/155 (7.7%)\nHyperhydrosis:  1/155 (0.6%) vs 5/157 (3.2%) vs 3/151 (2.0%) vs 1/148 (0.7%) vs 10/155 (6.5%)\nNasopharyngitis: 12/155 (7.7%) vs. 11/157 (7.0%) vs. 4/151 (2.5%) vs. 6/148 (4.1%) vs. 3/155 (1.9%)\nInsomnia: 8/155 (5.2%) vs. 11/157 (7.0%) vs. 3/151 (2.0%) vs. 6/148 (4.1%) vs. 13/155 (8.4%)\nFatigue:  1/155 (0.6%) vs 3/157 (1.9%) vs 3/151 (2.0%) vs 3/148 (2.0%) vs 8/155 (5.2%)\n","H. Lundbeck A/S","Randomization: Yes\nAllocation concealment: Yes\nSimilar groups at baseline: Yes\nEligibility criteria specified: Yes\nOutcome assessors masked: Yes\nCare providers masked: Yes\nPatients masked: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: Yes\nIntention-to-treat: Yes\nOverall rating: Fair"]
["Jain et al, 2012\nUS\n\nNCT00672958\n\n303\n","published","V: Vortioxetine 5 mg\nP: placebo","Patients with MDD major depressive episode of at least 3 months' duration according to DSM-IV-TR criteria; outpatient; 18-75 years old; baseline MADRS score ≥ 30 at baseline  ","Current psychiatric disorder other than MDD (assessed using MINI), or if current or past history neurological or substance abuse disorder, current clinically significant medical illness or clinically significant abnormalities in vital sighns or lab values. Concomitant use of any neuroactive medications prohibited 2-5 weeks prior to start of study and throughout treatment period. \n\nPatients at serious risk of suicide or who had score of ≥ 5 on item 10 of MADRS scale, or had made serious suicide attempt in previous 6 months.","n=600\n\nV5: 300 / 299\nP: 300 / 298 \n","V5  vs P\n\nAge:  42.5  ± 13.04 vs 42.4  ± 12.70  \nFemale: 62.0% vs 54.7% \nnon-White: 30% vs 28%\n","V5  vs P\n\nHAMD24: 32.7 vs. 32.2 \nMADRS: 34.1 vs. 34.0","6 weeks","V5 vs P\n\nResponse\nHAMD24: 135/292 (46.2%) vs. 132/286 (46.2%)\n\nRemission\nMADRS: 85/292 (29.1%) vs. 92/286 (32.2%)\n","V5 vs P\n\nMADRS: -15.8 (0.7) vs. -15.5 (0.7) \n\nHAMD24: -14.6 (0.65) vs. -13.87 (0.66)\n","V5 vs P\n\nWithdrawals due to adverse events: 9/299 (3.0%) vs. 11/298 (3.7%) \nSerious adverse event: 7/299 (2.3%) vs. 4/298 (1.3%)\nDeaths: None\n\nSpecific Adverse Events\nNausea: 57/299 (19.1%) vs. 28/298 (9.4%) \nVomiting*:  8/299 (2.7%) vs 4/298 (1.3%)\nHeadache: 51/299 (17.1%) vs. 45/298 (15.1%) \nDiarrhea: 34/299 (11.4%) vs. 21/298 (7.0%) \nDizziness 19/299 (6.4%) vs. 19/298 (7.4%)\nDry mouth: 25/299 (8.4%) vs. 19/298 (6.4%)\nHyperhydrosis*:  4/299 (1.3%) vs 7/298 (2.3%) \nNasopharyngitis*:  7/299 (2.3%) vs5/298 (1.7%) \nInsomnia:  6/299 (2.0%) vs 9/298 (3.0%)\nFatigue*:  5/299 (1.7%) vs 7/298 (2.3%)\n","Takeda Pharmaceutical company","Randomization: Yes\nAllocation concealment: Yes\nSimilar groups at baseline: Yes\nEligibility criteria specified: Yes\nOutcome assessors masked: Unclear\nCare providers masked: Yes\nPatients masked: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: Yes\nIntention-to-treat: Unclear\nOverall rating: Fair"]
["Katona et al, 2012\nCanada, Europe, US\n\n8-weeks\n\nNCT00811252\n\n12541A","published","V5: Vortioxetine 5 mg\nP: Placebo\nD: Duloxetine 60mg ","Patients with MDD presenting with current major depressive episode of at least 4 weeks according to DSM-IV-TR criteria; at least one previous major depressive episode before the age of 60; outpatient; ≥65 years old; MADRS total score ≥ 26 at screening and baseline visit ","Current psychiatric disorder othert than MDD (assessed using MINI), or if current or past history of manic or hypomanic episode, schipohrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition, any substance abuse disorder within the previous 6 months, presence or history of a clinically significant neurological disorder (including epilepsy), any neurodegenerative disorder, or any Axis II disorder that might compromise the study.\n\nPatients at serious risk of suicide or who had score of ≥ 5 on item 10 of MADRS scale, those receiving formal behaviour therapy or systematic psychotherapy, who had a known hypersensitivity to duloxetine or whose current depressive symptoms were considered by the investigator to have been reisitant to two adequate antidepressant treatments of at least 6 week duration, or had previously been exposed to Lu AA21004\n\nElevated IOP or at risk for acute angle glaucoma, chronic liver disease, clinically significant unstable illness, MI within previous 6 months, TSH level outside reference range at screening, hx of cancer in remission for less than 5 years, clinically significant abnormal vital signs","n=453\n\nV5: 157 / 156\nP: 145/ 145\nD: 151 / 151\n","V5 vs P vs D\n\nAge:  70.5  ± 4.8 vs 70.3  ± 4.4  vs 70.9  ± 5.5  \nFemale:  68.6% vs 62.0% vs 66.2%\nNon-white:  7.1% vs 4.1% vs 4.6%","V5 vs P vs D\n\nHAMD24: 29.2 vs. 29.4 vs. 28.5\nHAMD17: 22.7 vs. 22.7 vs. 22.3\nMADRS: 30.7 vs. 30.3 vs. 30.4\nHAMA: 19.9 vs. 19.5 vs. 19.2","8 weeks","V5 vs. P vs. D\n\nResponse\nMADRS: 92/154 (59.7%) vs. 52/145 (35.9%) vs. 104/147 (70.7%) \nHAMD24: 82/154 (53.2%) vs. 51/145 (35.2%) vs. 93/147 (63.3%)\n\nRemission\nMADRS: 52/154 (33.8%) vs. 30/145 (20.7%) vs. 69/147 (46.9%) \nHAMD17: 45/154 (29.2%) vs. 28/145 (19.3%) vs. 51/147 (34.7%) \n","V5 vs P vs D\n\nMADRS*: -15.5 (0.8) vs. -11.2 (0.8) vs. -18 (0.8)\n\nHAMD: -13.7 (0.7) vs. -10.3 (0.8) vs. -15.8 (0.8)\n\n","V5 vs P vs D\n\nWithdrawals due to adverse events: 10/156 (6.4%) vs. 6/145 (4.1%) vs. 15/151 (9.9%) \nSerious adverse event: 1/156 (<1%) vs. 4/145 (2.8%) vs. 1/151 (<1%) \nDeaths: None\n\nSpecific Adverse Events\nNausea: 34/156  (21.8%) vs. 12/145 (8.3%) vs. 50/151 (33.1%)\nVomiting:  not reported\nHeadache: 18/156 (11.5%) vs. 25/145  (17.2%) vs. 18/151 (11.9%) \nDiarrhea: 8/156  (5.1%) vs. 10/145 (6.9) vs. 14/151 (9.3%)\nDizziness: 14/156  (9.0%) vs. 10/145 (6.9%) vs. 14/151 (9.3%) \nDry mouth: 10/156  (6.4%) vs. 7/145 (4.7%) vs. 33/151 (21.9%) \nHyperhydrosis:  6/156 (3.8%) vs 4/145 (2.8%) vs 16/151 (10.6%)\nNasopharyngitis:  not reported\nInsomnia: not reported\nFatigue:  11/156 (7.1%) vs 5/145 (3.4%) vs 16/151 (10.6%)","H. Lundbeck A/S","Randomization: Yes\nAllocation concealment: Yes\nSimilar groups at baseline: Yes\nEligibility criteria specified: Yes\nOutcome assessors masked: Yes\nCare providers masked: Yes\nPatients masked: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: No\nIntention-to-treat: Yes\nOverall rating: Good"]
["Henigsberg et al, 2012\nAustralia, Europe, Asia, South Africa\n\n8 weeks\n\nNCT00735709\n\n305\n","published","V1: Vortioxetine 1 mg\nV5: Vortioxetine 5 mg\nV10: vortioxetine 10mg\nP: placebo","Patients with MDD presenting with current major depressive episode according to DSM-IV-TR criteria; outpatient; 18-75 years old; MADRS total score ≥ 26 at baseline visit ","Current psychiatric disorder other than MDD (assessed using MINI), or if current or past history neurological or substance abuse disorder, current clinically significant medical illness or clinically significant abnormalities in vital sighns or lab values. Concomitant use of any neuroactive medications prohibited 2-5 weeks prior to start of study and throughout treatment period. \n\nPatients at serious risk of suicide or who had score of ≥ 5 on item 10 of MADRS scale, or had made serious suicide attempt in previous 6 months.","n=560\n\nV1: 140 / 140\nV5: 140 / 140\nV10: 140 / 139\nP: 140 / 140\n","V1 vs V5 vs V10 vs P \n\nAge:  45.4  ± 11.89 vs 47.3  ± 11.95 vs 46.4  ± 12.27  vs 46.4  ± 12.26   \nFemale:  66.4% vs 62.1% vs 60.7% vs 61.4%\nNon-white: 7.9% vs 14.3% vs 18.6% vs 14.3%","V1 vs V5 vs V10 vs P \n\nHAMD24: 32.5 vs. 32.1 vs. 33.1 vs. 32.7\nMADRS: 30.4 vs. 30.6 vs. 31.6 vs. 30.6\n","8 weeks","V1 vs V5 vs V10 vs P \n\nResponse\nMADRS: 65/139 (46.8%) vs. 61/139 (43.9%) vs. 68/139 (48.9%) vs. 34/139 (24.5%) \nHAMD24: 66/139 (47.5%) vs. 63 /139(45.3%) vs. 69/139 (49.6%) vs. 32/139 (23.0%)\n\n\nRemission\nMADRS: 36/139 (25.9%) vs. 40/139 (28.8%) vs. 37/139 (26.6%) vs. 23/139 (16.5%) \nHAMD17: 29/139 (20.9%) vs. 34/139 (24.5%) vs. 33/139 (23.7%) vs. 16/139 (11.5%) \n","V1 vs V5 vs V10 vs P \n\nMADRS:  -14.9 (0.7) vs. -15.1 (0.7) vs. -15.7 (0.7) vs. -10.9 (0.7)\n\nHAMD24: -14.8 (0.7)  vs. -15.4 (0.7) vs. -16.23 (0.8) vs. -11.3 (0.7)\n\n","V1 vs V5 vs V10 vs P \n\nWithdrawals due to adverse events:  3/140 (2.1%) vs. 1/140 (0.7%) vs. 5/139 (3.6%) vs. 2/140 (1.4%)\nSerious adverse event: 1/140 (0.7%) vs. 1/140 (0.7%) vs. 2/139 (1.4%) vs. 2/140 (1.4%)\nDeaths: None\n\nSpecific Adverse Events\nNausea: 11/140  (7.9%) vs 22/140 (15.7%)  vs 18/139 (12.9%) vs 6/140 (4.3%)\nVomiting:  not reported\nHeadache: 9/140  (6.4%) vs. 16/140 (11.4%) vs. 7/139 (5.0%) vs. 11/140 (7.9%)\nDiarrhea*:  2/140 (1.4%) vs 3/140 (2.1%) vs 4/139 (2.9%) vs 28/140 (1.4%) \nDizziness: 1/140  (0.7%) vs. 5/140 (3.6%) vs. 9/139 (6.5%) vs. 3/140 (2.1%)\nDry mouth*:  2/140 (1.4%) vs 3/140 (2.1%) vs 3/139 (2.2%) vs 3/140 (2.1%)\nHyperhydrosis*:  0/140 (0%) vs 3/140 (2.1%) vs 2/139 (1.4%) vs 1/140 (0.7%) \nNasopharyngitis: 5/140  (3.6%) vs. 7/140 (5.0%) vs. 3/139 (2.2%) vs. 8/140 (5.7%)\nInsomnia:  not reported\nFatigue*:  3/140 (2.1%) vs 5/140 (3.6%) vs 1/139 (0.7%) vs 0/140 (0%)\n","Takeda Pharmaceutical company","Randomization: Unclear\nAllocation concealment: Unclear\nSimilar groups at baseline: Yes\nEligibility criteria specified: Yes\nOutcome assessors masked: Unclear\nCare providers masked: Yes\nPatients masked: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: No\nIntention-to-treat: No\nOverall rating: Poor"]
["Boulenger et al, 2013\nEurope, South Africa\n\nNCT01140906\n\n13267A\n","published","V15: Vortioxetine 15mg\nV20: vortioxetine 20mg\nP: Placebo\nD: duloxetine 60 mg","Patients with MDD presenting with current major depressive episode (>3 months) according to DSM-IV-TR criteria; outpatient; 18-75 years old; MADRS total score ≥ 26 at baseline visit, CGI-S score  4 ","Current psychiatric disorder othert than MDD (assessed using MINI), or if current or past history of manic or hypomanic episode, schipohrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition, any substance abuse disorder within the previous 6 months, presence or history of a clinically significant neurological disorder (including epilepsy), any neurodegenerative disorder, or any Axis II disorder that might compromise the study.\n\nPatients at serious risk of suicide or who had score of ≥ 5 on item 10 of MADRS scale, those receiving formal behaviour therapy or systematic psychotherapy, who had a known hypersensitivity to duloxetine or whose current depressive symptoms were considered by the investigator to have been reisitant to two adequate antidepressant treatments of at least 6 week duration, or had previously been exposed to Lu AA21004\n\nElevated IOP or at risk for acute angle glaucoma, chronic liver disease, clinically significant unstable illness, MI within previous 6 months, TSH level outside reference range at screening, hx of cancer in remission for less than 5 years, clinically significant abnormal vital signs","n=608\n\nV15:  152 / 151\nV20:  151 / 151\nP:  158 / 158\nD:  147 / 147\n","V15 vs V20 vs P vs D \n\nAge:  47.1±14.6 vs 46.2±13.4 vs 48.1±13.1 vs 45.6±13.6 \nFemale:  64.2% vs 60.3% vs 69.6% vs 69.4%\nNon-white:  0.7% vs 3.3% vs 1.3% vs 2.0%","V15 vs V20 vs P vs D \n\nMADRS: 31.8 vs 31.2 vs 31.5 vs 31.2\nHAMA: 21.3 vs 20.4 vs 20.8 vs 20.5","8 weeks","V15 vs V20 vs P vs D \n\nResponse\nMADRS: 85/149 (57.0%) vs 93/151 (61.6%) vs 51/158 (32.3%) vs 108/146 (74.0%)\n\nRemission\nMADRS: 52/149 (34.9%) vs 58/151 (38.4%) vs 30/158 (19.0%) vs 79/146 (54.1%)","V15 vs V20 vs P vs D \n\nMADRS*: -17.2 (0.8) vs -18.8 (0.8) vs -11.7(0.8) vs -21.2 (0.8)\n\nHAMD24:  not reported","V15 vs V20 vs P vs D \n\nWithdrawals due to adverse events:  10/151 (6.6%) vs. 17/151 (11.3%) vs. 7/158 (4.4%) vs. 7/147 (4.8%)\nSerious adverse event: 0/151 (0%) vs. 2/151 (1.3%) vs. 0/158 (0%)   vs. 3/147 (2.0%)\nDeaths: None\n\nSpecific Adverse Events\nNausea: 40/151 (26.5%) vs. 48/151 (31.8%) vs. 16/158 (10.1%) vs. 45/147  (30.6%)\nVomiting: not reported\nHeadache: 16/151 (10.6%) vs. 19/151 (12.6%) vs. 12/158 (7.6%) vs. 16/147  (10.9%)\nDiarrhea:  6/151 (4.0%) vs.11/151 (7.3%) vs. 6/158 (3.8%) vs. 9/147  (6.1%)\nDizziness: 7/151 (4.6%) vs. 8/151 (5.3%) vs. 10/158 (6.3%) vs. 15/147  (10.2%)\nDry mouth: 5/151 (3.3%) vs. 9/151 (6.0%) vs. 5/158 (3.2%) vs. 14/147  (9.5%)\nHyperhydrosis:  5/151 (3.3%) vs 0/151 (0%) vs 6/158 (3.8%) vs 11/147 (7.5%)\nNasopharyngitis:  not reported\nInsomnia:  not reported\nFatigue:  6/151 (4.0%) vs 5/151 (3.3%) vs 4/158 (2.5%) vs 8/147 (5.4%)","H. Lundbeck A/S","Randomization: Yes\nAllocation concealment: Yes\nSimilar groups at baseline: Yes\nEligibility criteria specified: Yes\nOutcome assessors masked: Unclear\nCare providers masked: Yes\nPatients masked: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: Yes\nIntention-to-treat: Yes\nOverall rating: Fair"]
["315\nUS\n\nNCT01153009","Dossier, FDA summary review","V15: vortioxetine 15 mg\nV20: vortioxetine 20mg\nP: placebo\nD: duloxetine 60mg","Patients with MDD presenting with current major depressive episode (>3 months) according to DSM-IV-TR criteria; outpatient; 18-75 years old; MADRS total score ≥ 26 at baseline visit, CGI-S score  4 ","Current psychiatric disorder other than MDD (assessed using MINI), or if current or past history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition, any substance abuse disorder within the previous 6 months, presence or history of a clinically significant neurological disorder (including epilepsy), any neurodegenerative disorder, or any Axis II disorder that might compromise the study.\n\nPatients at serious risk of suicide or who had score of ≥ 5 on item 10 of MADRS scale, those receiving formal behavior therapy or systematic psychotherapy, who had a known hypersensitivity to duloxetine or whose current depressive symptoms were considered by the investigator to have been reisitant to two adequate antidepressant treatments of at least 6 week duration, or had previously been exposed to Lu AA21004\n\nElevated IOP or at risk for acute angle glaucoma, chronic liver disease, clinically significant unstable illness, MI within previous 6 months, TSH level outside reference range at screening, hx of cancer in remission for less than 5 years, clinically significant abnormal vital signs","n=614\n\nV15: 147 / 147\nV20: 154 / 154\nP: 161 / 159\nD: 152 / 150","V15 vs V20 vs P vs D \n\nAge:  43.1  ± 12.28 vs 42.8  ± 12.40 vs 42.4  ± 12.55  vs 43.4  ± 12.24  \nFemale: 70.7% vs 74.0% vs 72.0% vs 78.3%\nnon-white: 22.4% vs 25.3% vs 24.2% vs 22.7%","V15 vs V20 vs P vs D \n\nMADRS: 31.9 vs 32.0 vs 31.5 vs 32.8\nHAMA: 17.5 vs 17.7 vs 17.0 vs 18.2","8 weeks","V15 vs V20 vs P vs D \n\nResponse\nMADRS: 64/145 (44.1%)  vs 65/147 (44.2%) vs 60/153 (39.2%) vs 80/146 (54.8%)\n\nRemission\nMADRS: 39/145 (26.9%)  vs 43/147 (29.3%) vs 41/153 (26.8%) vs 38/152 (26.0%)","V15 vs V20 vs P vs D \n\nMADRS*: -14.3 (0.9)  vs -15.6 (0.9)  vs -12.8 (0.8)  vs -16.9 (0.9)\n\nHAMD24:  not reported\n","V15 vs V20 vs P vs D \n\nWithdrawal due to adverse events: 14/147 (9.5%) vs 14/154 (9.1%) vs 4/159 (2.5%) vs 10/150 (6.7%)\nSerious adverse events: 2/147 (1.4%)  vs 0/154 (0%) vs 0/159 (0%) vs 0/150 (0%)\nDeaths: none\n\nSpecific Adverse Events\nNausea: 52/147 (35.4%) vs 51/154  (33.1%) vs 18/159 (11.3%) vs 55/150 (36.7%)\nVomiting: 7/147 (4.8%) vs 13/154  (8.4%) vs 1/159 (0.6%) vs 12/150 (8.0%)\nHeadache:  26/147 (17.7%) vs 20/154 (13.0%) vs 21/159 (13.2%) vs 28/150 (18.7%)\nDiarrhea: 22/147 (15.0%) vs 12/154  (7.8%) vs 10/159 (6.3%) vs 18/150 (12.7%)\nDizziness: 15/147 (10.2%) vs 20/154  (13.0%) vs 5/159 (3.1%) vs 24/150 (16.0%)\nDry mouth: 14/147 (9.5%) vs 33/154  (14.3%) vs 16/159 (10.1%) vs 26/150 (17.3%)\nHyperhydrosis:  not reported\nNasopharyngitis:  6/147 (4.1%) vs 9/154 (5.8%) vs 10/159 (6.3%) vs 5/150 (3.3%)\nInsomnia: 5/147 (3.4%0 vs 13/154 (8.4%) vs 8/159 (3.8%) vs 14/150 (9.3%)\nFatigue:  7/147 (4.8%) vs 8/154 (5.2%) vs 4/159 (2.5%) vs 17/150 (11.3%) ",null,"Similar groups at baseline: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: Yes\nIntention-to-treat: Yes\nOverall rating:Fair/Unclear"]
["316\nUS\n\nNCT01163266","Dossier, FDA summary review","V10: vortioxetine 10 mg\nV20: vortioxetine 20mg\nP: placebo","Patients with MDD presenting with current major depressive episode (>3 months) according to DSM-IV-TR criteria; outpatient; 18-75 years old; MADRS total score ≥ 26 at baseline visit, CGI-S score  4 ","Current psychiatric disorder other than MDD (assessed using MINI), or if current or past history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition, any substance abuse disorder within the previous 6 months, presence or history of a clinically significant neurological disorder (including epilepsy), any neurodegenerative disorder, or any Axis II disorder that might compromise the study.\n\nPatients at serious risk of suicide or who had score of ≥ 5 on item 10 of MADRS scale, those receiving formal behavior therapy or systematic psychotherapy, who had a known hypersensitivity to duloxetine or whose current depressive symptoms were considered by the investigator to have been reisitant to two adequate antidepressant treatments of at least 6 week duration, or had previously been exposed to Lu AA21004\n\nElevated IOP or at risk for acute angle glaucoma, chronic liver disease, clinically significant unstable illness, MI within previous 6 months, TSH level outside reference range at screening, hx of cancer in remission for less than 5 years, clinically significant abnormal vital signs","n=462\n\nV10: 155 / 155\nV20: 150 / 150\nP: 157 / 157","V10 vs V20 vs P \n\nAge: 43.1  ± 12.04 vs 43.1  ± 13.09 vs 42.3  ± 11.61     \nFemale: 76.1% vs 71.3% vs 70.1%\nnon-white: 31.6% vs 30.7% vs 23.6%","V10 vs V20 vs P \n\nMADRS: 32.3 vs 32.4 vs 32.0\n\nHAMA: 18.5 vs 18.9 vs 17.8","8 weeks","V10 vs V20 vs P \n\nResponse\nMADRS: 52/154 (33.8%) vs 58/148 (39.2%) vs 44/155 (28.4%)\n\nRemission\nMADRS: 33/154 (21.4%) vs 33/148 (22.3%)  vs 22/155 (14.2%)","V10 vs V20 vs P \n\nMADRS*: -13.0 (0.8) vs -14.4 (0.8) vs -10.8 (0.8)\n\nHAMD24:  not reported","V10 vs V20 vs P \n\nWithdrawal due to adverse evants: 9/155 (5.8%) vs 7/150 (4.7%) vs 2/157 (1.3%) \nSerious adverse events: 2/155 (1.3%) vs 0/150 (0%) vs 0/157 (0%)\nDeaths: none\n\nSpecific Adverse Events\nNausea: 42/155  (27.1%) vs 44/150 (29.3%) vs 8/157 (5.1%)\nVomiting: 9/155  (5.8%) vs 8/150 (5.3%) vs 3/157 (1.9%)\nHeadache: 24/155  (15.5%) vs 24/150 (16.0%) vs 17/157 (10.8%)\nDiarrhea: 20/155  (12.9%) vs 11/150 (7.3%) vs 14/157 (8.9%) \nDizziness: 13/155  (8.4%) vs 9/150 (6.0%) vs 9/157 (5.7%)\nDry mouth: 7/155  (4.5%) vs 7/150 (4.7%) vs 15/157 (9.6%)\nHyperhydrosis: not reported\nNasopharyngitis: 4/155 (2.6%) vs 7/150 (4.7%) vs 1/157 (0.6%)\nInsomnia:  6/155 (3.9%) vs 3/150 (2.0%) vs 6/157 (3.8%)\nFatigue:  9/155 (5.8%) vs 0/150 (0%) vs 9/157 (5.7%)",null,"Similar groups at baseline: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: No\nIntention-to-treat: Yes\nOverall rating: Fair/ Unclear"]
["317\nUS\n\nNCT01179516","ClinicalTrials.gov, FDA summary review","V10: vortioxetine 10 mg\nV20: vortioxetine 15mg\nP: placebo",null,null,"n=434\n\nV10:  143\nV15:  142\nP:  149","V10 vs V20 vs P \n\nAge: 45.2  ± 11.94 vs 43.8  ± 13.51 vs 46.2  ± 11.79 \nFemale: 72.0% vs 71.1% vs 67.5%\nNon-White: 26.8% vs 28.3% vs 22.5%","V10 vs V20 vs P \n\nMADRS: 34.1 vs 33.6 vs 33.4\nHAMA: 201 vs 19.5 vs 20.0 \n","8 weeks","V10 vs V20 vs P\n\n\nResponse\nMADRS:  54/143 (37.8%) vs 53/142  (37.3%) vs 49/149 (32.9%)\n\nRemission\nMADRS:  38/143 (26.6%) vs 34/142 (23.9%) vs 33/149 (22.1%)","V10 vs V20 vs P \n\nMADRS*: -13.7 (1.1) vs -13.4 (1.1) vs -12.9 (1.0)\n\nHAMD24:  not reported","V10 vs V20 vs P \n\nWithdrawals due to adverse events:  8/154 (5.2%) vs 12/151 (7.9%) vs 6/160 (3.8%)\nSerious Adverse Events: 1/154 (0.6%) vs 0/151 (0%) vs 1/160 (0%)\n\nSpecific Adverse Events\nNausea: 47/154 (30.5%) vs 51/151 (33.8%) vs 17/160 (10.6%)\nVomiting: 7/154 (4.5%) vs 18/151 (11.9%)  vs 4/160 (2.5%)\nHeadache: 24/154 (15.6%) vs 25/151 (16.6%) vs 29/160 (18.1%)\nDiarrhea: 10/154 (6.5%) vs 15/151 (9.9%)  vs 10/160 (6.3%)\nDizziness:  6/154 (3.9%) vs 12/151 (7.9%) vs 15/160 (9.4%)\nDry mouth: 24/154 (15.6%) vs 8/151 (5.3%) vs 11/160 (6.9%)\nHyperhydrosis: not reported\nNasopharyngitis: 6/154 (3.9%) vs 3/151 (2.0%) vs 8/160 (5.0%)\nInsomnia: 4/154 (2.6%) vs 6/151 (4.0%) vs 4/160 (2.5%)\nFatigue:  4/154 (3.2%) vs 4/151 (2.6%) vs 8/160 (5.0%)\n",null,"Similar groups at baseline: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: No\nIntention-to-treat: Yes\nOverall rating: Fair/Unclear"]
["FOCUS\nUS, Australia, Canada, Europe\n\nNCT01422213","Dossier","V10: vortioxetine 10 mg\nV20: vortioxetine 20mg\nP: placebo","18-65 years, recurrent MDD, current MDE of ≥3 months, MADRS total score≥26","Presence of Axis 1 disorder, score of ≥70 on DSST, ≥42 on RAVLT (learning), or ≥ 14 on RAVLT (memory); resistance to 2 adequate courses of antidepressant treatment; use of antidepressant within 2 weeks of screening (5 weeks for fluoxetine); clinically significant unstable illness; alcohol or substance abuse not in full remission ≥2 years; preganancy or females unwilling to use contraception, abnormal vital signs, ECG or lab values","n=598\n\nV10: 195\nV20: 207\nP: 196","V10 vs V20 vs P \n\nAge: 45.4±12.2 vs 46.1±11.8 vs 45.6±12.1 \nFemale: 68.7% vs 64.3% vs 65.8%\nNon-White: 6.2%  vs 6.3% vs 4.1%","V10 vs V20 vs P \n\n MADRS: 31.6 vs 31.7 vs 31.3 vs 31.6","8 weeks","V10 vs V20 vs P \n\nResponse\nMADRS: 94/195 (48.2%) vs 122/207 (58.9%) vs 57/196 (29.1%)\n\nRemission\nMADRS: 59/195 (30.3%) vs 79/207 (38.2%) vs 33/196 (16.8%)","V10 vs V20 vs P \n\nMADRS (difference from placebo):  -4.7 vs -6.7\n\nHAMD24:  not reported","V10 vs V20 vs P \n\nWithdrawals due to adverse events:  7/195 (3.6%) vs 8/207 (4.1%) vs 9/196 (4.8%)\nSerious Adverse Events:  0/195 (0%) vs 2/207 (1.0%) vs 2/196 (1.0%)\nDeaths:  none\n\nSpecific Adverse Events\nNausea: 32/195 (16.4%) vs 43/207 (20.8%) vs 8/196 (4.1%)\nVomiting:  not reported\nHeadache: 16/195  (8.2%) vs 26/207  (12.6%) vs 14/196 (7.1%)\nDiarrhea: not reported\nDizziness: not reported\nDry mouth: not reported\nHyperhydrosis: not reported\nNasopharyngitis:  7/195 (3.6%) vs 9/207  (4.3%) vs 10/196 (5.1%)\nInsomnia: not reported\nFatigue: not reported\n",null,"Randomization: Yes\nAllocation concealment: Yes\nSimilar groups at baseline: Yes\nEligibility criteria specified: Yes\nOutcome assessors masked: Unclear\nCare providers masked: Yes\nPatients masked: Yes\nAttirition/withdrawal reported: Yes\nAttirition/withdrawal differential high: No\nIntention-to-treat: Yes\nOverall rating: Good"]