Levomilnacipran and vortioxetine: Review of new pharmacotherapies for major depressive disorder

Table 4 Randomized controlled trials of vortioxetine for major depressive disorder[21-23,27,29,31-36]

Ref.	n	Duration	Key inclusion criteria	Doses	Primary outcome
Alvarez et al[21] Phase II	429	6 wk	Age 18-65 yr MADRS ≥ 30	Vortioxetine 5 mg/d Vortioxetine 10 mg/d Placebo Venlafaxine XR 225 mg/d	Positive Change from baseline in MADRS Placebo: -14.5 5 mg: -20.4 (P < 0.001) 10 mg: -20.2 (P < 0.001) Venlafaxine: -20.9 (P < 0.001)
Baldwin et al[29] Phase III	776	8 wk	Age 18-75 yr MADRS ≥ 26	Vortioxetine 2.5 mg/d Vortioxetine 5 mg/d Vortioxetine 10 mg/d Placebo Duloxetine 60 mg/d	Failed Change from baseline in MADRS Placebo: -14.8 2.5 mg: -16.2 (P = 0.219) 5 mg: -16.5 (P = 0.132) 10 mg: -16.3 (P = 0.185) Duloxetine: -16.8 (P = 0.074)
Jain et al[32] Phase III	600	6 wk	Age 18-75 yr MADRS ≥ 30	Vortioxetine 5 mg/d Placebo	Negative/failed Change from baseline in HAM-D24 Placebo: -13.87 5 mg: -14.61 (P = 0.407)
Mahableshwarkar et al[33] Phase III	611	8 wk	Age 18-75 yr MADRS ≥ 22	Vortioxetine 2.5 mg/d Vortioxetine 5 mg/d Placebo Duloxetine 60 mg/d	Negative Change from baseline in HAM-D24 Placebo: -10.5 2.5 mg: -12.05 (P = 0.138) 5 mg: -11.08 (P = 0.577) Duloxetine: -13.47 (P = 0.005)
Henigsberg[23] Phase III	560	8 wk	Age 18-75 yr MADRS ≥ 26	Vortioxetine 1 mg/d Vortioxetine 5 mg/d Vortioxetine 10 mg/d Placebo	Positive Change from baseline in HAM-D24 Placebo: -11.3 1 mg: -14.82 (P < 0.001) 5 mg: -15.42 (P < 0.001) 10 mg: -16.23 (P < 0.001)
Boulenger et al[31] Phase III	608	8 wk	Age 18-75 yr MADRS ≥ 26	Vortioxetine 15 mg/d Vortioxetine 20 mg/d Placebo Duloxetine 60 mg/d	Positive Change from baseline in MADRS Placebo: -11.7 15 mg: -17.2 (P < 0.0001) 20 mg: -18.8 (P < 0.0001) Duloxetine: -21.2 (P < 0.0001)
NCT01153009[34] Phase III	614	8 wk	Age 18-75 yr MADRS ≥ 26	Vortioxetine 15 mg/d Vortioxetine 20 mg/d Placebo Duloxetine 60 mg/d	Positive Change from baseline in MADRS Placebo: -12.83 15 mg: -14.3 (NS) 20 mg: -15.57 (P < 0.05) Duloxetine: -16.9 (P < 0.001)
NCT01163266[36] Phase III	462	8 wk	Age 18-75 yr MADRS ≥ 26	Vortioxetine 10 mg/d Vortioxetine 20 mg/d Placebo	Positive Change from baseline in MADRS Placebo: -10.8 10 mg: -13.0 (NS) 20 mg: -14.4 (P < 0.01)
NCT01179516[35] Phase III	469	8 wk	Age 18-75 yr MADRS ≥ 26	Vortioxetine 10 mg/d Vortioxetine 15 mg/d Placebo	Negative/failed Change from baseline in MADRS Placebo: -12.87 10 mg: -13.66 (P = 0.597) 15 mg: -13.36 (P = 0.745)
NCT01255787[27] (unpublished) Phase III	600	8 wk	Age 20-64 yr MADRS ≥ 26	Vortioxetine 5 mg/d Vortioxetine 10 mg/d Vortioxetine 20 mg/d Placebo	Negative Change from baseline in MADRS Placebo: -13.99 5 mg: -14.61 (P = 0.907) 10 mg: -15.68 (P = 0.301) 20 mg: -15.82 (P = 0.240)
Boulenger et al[22] Phase III	400	24-64 wk	Age 18-75 yr MADRS ≥ 26	Vortioxetine 5-10 mg/d Placebo	Positive Time to relapse-vortioxetine vs placebo HR = 2.01 (95%CI: 1.26-3.21) (P = 0.0035)

NCT: National clinical trial; MADRS: Montgomery-Asberg Depression Rating Scale; HAM-D₂₄: Hamilton Rating Scale for Depression (24-items).