Table 3.

Summary of main efficacy results of short-term (6- to 12-weeks) randomized trials of vortioxetine for major depressive disorder in adults

References/registrationa	Primary endpoint	Outcome	Main efficacy results
			Group	Depressive symptoms, change from baseline	Completion rates, %	Response rates, %	Remission rates, %
Alvarez et al49 #NCT00839423	Change in MADRS total score over 6 weeks	Positiveb,c	Vortioxetine 5 mg	−21.3 (0.9)****,d	90†	67**	49**
			Vortioxetine 10 mg	−22.9 (1.1)****	81	68**	49**
			Venlafaxine 225 mg	−23.4 (0.9)****	82	72***	55***
			Placebo	−15.7 (1.0)	83	45	27
Henigsberg et al50 #NCT00735709	Change in HDRS-24 total score over 8 weeks	Positivee,f	Vortioxetine 1 mg	−14.8 (0.7)**,d	91†	48***	21*
			Vortioxetine 5 mg	−15.4 (0.7)**	92	45***	25**
			Vortioxetine 10 mg	−16.2 (0.8)***	87	50***	24**
			Placebo	−11.3 (0.7)	91	23	12
Katona et al51 #NCT00811252	Change in HDRS-24 total score over 8 weeks	Positiveb,f	Vortioxetine 5 mg	−14.7 (0.7)****,d	87†	53**	29*
			Duloxetine 60 mg	−17.0 (0.7)****	85	63***	35**
			Placebo	−10.8 (0.7)	88	35	19
Jain et al52 #NCT00672958	Change in HDRS-24 total score over 6 weeks	Negativeg	Vortioxetine 5 mg	−14.6 (0.7)h	81†	46	29
			Placebo	−13.9 (0.7)	78	46	32
Mahableshwarkar et al53 #NCT00672620	Change in HDRS-24 total score over 8 weeks	Negativeg	Vortioxetine 2.5 mg	−12.0 (0.7)h	65†	41	29†
			Vortioxetine 5 mg	−11.1 (0.7)	80	38	24
			Duloxetine 60 mg	−13.5 (0.8)**	72	51***	38
			Placebo	−10.5 (0.8)	78	32	23
Boulenger et al54 #NCT01140906	Change in MADRS total score over 8 weeks	Positiveb,c	Vortioxetine 15 mg	−17.2i	78	57****	35**
			Vortioxetine 20 mg	−18.8	83	62****	38***
			Duloxetine 60 mg	−21.2	89	74****	54****
			Placebo	−11.7	84	32	19
McIntyre et al55 #NCT01422213	Change in cognitive measures over 8 weeks Depressive symptoms measured using MADRS	Positivej	Vortioxetine 10 mg	−15.6 (0.6)***	91†	48**	30**
			Vortioxetine 20 mg	−17.6 (0.6)***	92	59***	38***
			Placebo	−10.9 (0.6)	91	29	17
Montgomery et al56 #NCT01488071	Change in MADRS total score over 12 weeks	Vortioxetine non-inferior and superior to agomelatinek	Vortioxetine 10–20 mg	−16.5 (0.5)‡,d	78	70‡‡	55‡‡‡
			Agomelatine 25–50 mg	−14.4 (0.5)	83	56	39
Baldwin et al57 #NCT00635219	Change in MADRS total score over 8 weeks	Failed studyl	Vortioxetine 2.5 mg	−16.2 (0.8)h	84	61	38
			Vortioxetine 5 mg	−16.5 (0.8)	77	64	43
			Vortioxetine 10 mg	−16.3 (0.8)	77	69*	45
			Duloxetine 50 mg	−16.8 (0.8)	72	71**	44
			Placebo	−14.8 (0.8)	82	Not reported	Not reported
Jacobsen et al58 #NCT01163266	Change in MADRS total score over 8 weeks	Positivec,e	Vortioxetine 10 mg	−13.0 (0.8)d	80†	34	21
			Vortioxetine 20 mg	−14.4 (0.8)**	81	39*	22
			Placebo	−10.8 (0.8)	89	28	14
Mahableshwarkar et al59 #NCT01179516	Change in MADRS total score over 8 weeks	Negativec	Vortioxetine 10 mg	−13.7 (1.1)d	83†	38	27
			Vortioxetine 15 mg	−13.4 (1.1)	80	37	24
			Placebo	−12.9 (1.0)	83	33	22
Unpublished study #NCT01153009	Change in MADRS total score over 8 weeks	Positiveb,c	Vortioxetine 15 mg	−14.3 (0.9)d	77†	44	27
			Vortioxetine 20 mg	−15.6 (0.9)*	73	44	29
			Duloxetine 60 mg	−16.9 (0.9)***	76	55**	26
			Placebo	−12.8 (0.8)	80	39	27
Unpublished study #NCT01255787	Change in MADRS total score over 8 weeks	Negativec	Vortioxetine 5 mg	−14.6 (0.8)m	88†	49†	25†
			Vortioxetine 10 mg	−15.7 (0.8)	88	54	29
			Vortioxetine 20 mg	−15.8 (0.8)	86	51	31
			Placebo	−14.0 (0.8)	89	39	27
Unpublished study #NCT01355081	Change in MADRS total score over 8 weeks	Negativec	Vortioxetine 5 mg	−15.8 (0.9)m	94†	51†	29†
			Vortioxetine 10 mg	−14.9 (0.9)	92	46	29
			Placebo	−13.8 (0.9)	91	40	22

Notes:

^*P≤0.05 versus placebo;

^**P≤0.01 versus placebo;

^***P≤0.001 versus placebo;

^****P≤0.0001 versus placebo;

^†no statistical comparison versus placebo was presented;

^‡P≤0.05 versus active comparator;

^‡‡P≤0.01 versus active comparator;

^‡‡‡P≤0.001 versus active comparator.

^aRegistration refers to the ClinicalTrials.gov identifier.

^bPositive result indicates significantly greater improvement in the primary efficacy endpoint for at least one vortioxetine dose group and the active comparator group, as compared with the placebo group.

^cPositive treatment response was defined as >50% reduction (improvement) from baseline in MADRS total score, whereas remission was defined as MADRS total score ≤10 at the end of follow-up.

^dResults from a mixed model repeated measures analysis are presented as mean (SE) change from baseline depressive symptom measure score.

^ePositive result indicates significantly greater improvement in the primary efficacy endpoint for at least one vortioxetine dose group, as compared with the placebo group.

^fPositive treatment response was defined as ≥50% reduction (improvement) from baseline in HDRS-24 total score, whereas remission was defined as HDRS-24 total score ≤7 at week 8.

^gPositive treatment response was defined as ≥50% reduction (improvement) from baseline in HDRS-24 total score, whereas remission was defined as MADRS total score ≤10 at week 6.

^hResults from analysis of covariance (controlling for treatment center and baseline value of dependent measures) are presented as mean (SE) change from baseline in depressive symptoms measure score.

ⁱResults from a mixed model repeated measures analysis are presented as mean changes from baseline depression symptom measure scores. No SE data were available.

^jThe purpose of this study was to examine the effects of vortioxetine (versus placebo) on cognitive functioning in depressed adults; however, secondary efficacy measures were also assessed. Positive result in this case is defined as significantly greater improvement in total symptom depressive scores between baseline and the end of follow-up.

^kThe purpose of this study was to compare the effects of vortioxetine and agomelatine on depressive symptoms in depressed adults who had inadequate responses to selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor treatment. The primary efficacy endpoint was analyzed using both a non-inferiority and superiority approach.

^lThe term “failed study” indicates that neither the vortioxetine dose group nor the duloxetine group showed significantly greater improvement in the primary efficacy measure than the placebo group. Positive response was defined as ≥50% reduction (improvement) from baseline in MADRS total score, whereas remission was defined as a MADRS total score of ≤10 at week 8. Response and remission rates are shown for observed cases only.

^mResults from analysis of covariance (controlling for baseline value of dependent measures) are presented as mean (SE) change from baseline in depressive symptoms measure score.

Abbreviations: HDRS-24, 24-item Hamilton Depression Rating Scale; MADRS, Montgomery-Åsberg Depression Rating Scale; SE, standard error.