A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine

Stuart A Montgomery, Rebecca Z Nielsen, Lis H Poulsen, Lars Häggström, Stuart A Montgomery, Rebecca Z Nielsen, Lis H Poulsen, Lars Häggström

Abstract

Objective: This randomised, double-blind, 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine(10-20 mg/day) versus agomelatine (25-50 mg/day) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin-noradrenaline reuptake inhibitor (SNRI) monotherapy.

Methods: Patients were switched directly from SSRI/SNRI to vortioxetine or agomelatine. Primary endpoint was change from baseline to week 8 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score analysed by mixed model for repeated measurements, using a noninferiority test followed by a superiority test. Secondary endpoints included response and remission rates, anxiety symptoms(Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life(EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale).

Results: Primary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p<0.01). Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12; MADRS, Hamilton Anxiety Rating Scale, Clinical Global Impression, Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards; work limitation questionnaire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12. Fewer patients withdrew because of adverse events with vortioxetine (5.9% vs 9.5%). Adverse events (incidence ≥5%) were nausea, headache, dizziness and somnolence.

Conclusions: Vortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy. Vortioxetine was safe and well tolerated.

Trial registration: ClinicalTrials.gov NCT01488071.

Figures

Figure 1
Figure 1
Flow chart of patient disposition. MADRS, Montgomery–Åsberg Depression Rating Scale; BL, baseline; APTS, all-patients-treated set; FAS, full-analysis set
Figure 2
Figure 2
Montgomery–Åsberg Depression Rating Scale (MADRS) response (≥50% improvement from baseline) and MADRS remission (MADRS total score ≤10) rates (logistic regression, full-analysis set and last observation carried forward). **p < 0.01; ***p < 0.001 versus agomelatine
Figure 3
Figure 3
Estimated change in Montgomery–Åsberg Depression Rating Scale (MADRS) total scores from baseline to week 12 (FAS and MMRM by visit) and LOCF (FAS and ANCOVA) at week 12. FAS, full-analysis set; LOCF, last observation carried forward; MMRM, mixed model repeated measures. Patient numbers at each visit are shown below the x-axis for each treatment group. **p < 0.01; ***p < 0.001 versus agomelatine. The primary endpoint is at week 8 (FAS and MMRM)
Figure 4
Figure 4
Estimated change in Hamilton Anxiety Rating Scale (HAM-A) total scores from baseline to week 12 (FAS and MMRM by visit) and LOCF (FAS and ANCOVA) at week 12. FAS, full-analysis set; LOCF, last observation carried forward; MMRM, mixed model repeated measures. Patient numbers at each visit are shown below the x-axis for each treatment group. **p < 0.01, ***p < 0.001 versus agomelatine

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