Randomized, double‐blind, placebo‐controlled study to assess the efficacy and safety of vortioxetine in Japanese patients with major depressive disorder

Inoue, Takeshi; Sasai, Kiyofumi; Kitagawa, T; Nishimura, Akira; Inada, Isao

doi:10.1111/pcn.12956

Cited by 31 publications

(53 citation statements)

References 37 publications

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“…Pooled data were analyzed from the six short-term (8-week), randomized, double-blind, placebo-controlled, fixed-dose studies conducted by Takeda/Lundbeck that included vortioxetine 20 mg/ day for the treatment of MDD. [10][11][12][13][14][15] Patients randomized to vortioxetine 20 mg/day received vortioxetine 10 mg/day for the first week, and then 20 mg/day for the remaining 7 weeks of the study period. In all studies, efficacy was assessed using the MADRS as a primary endpoint.…”

Section: Data Sourcesmentioning

confidence: 99%

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Vortioxetine 20 mg/day in patients with major depressive disorder: updated analysis of efficacy, safety, and optimal timing of dose adjustment

et al. 2021

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Background. Analysis of efficacy and tolerability of vortioxetine 20 mg/day, and optimal timing of dose adjustment, in patients with major depressive disorder (MDD). Methods. Pooled analysis of six randomized, fixed-dose studies of vortioxetine 5 to 20 mg/day. Mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was analyzed by vortioxetine dose using a mixed model for repeated measures. Tolerability was assessed over the 8-week treatment period and from day 8 (ie, following dose increase to 20 mg/day). Data from three randomized, flexible-dose studies were examined for frequency and timing of dose adjustment. Results. A clear dose-response relationship for vortioxetine was confirmed in terms of improvement in MADRS total score. Significant differences vs placebo were seen for vortioxetine 20 mg/day from week 2 onwards; vortioxetine 10 mg did not separate from placebo until week 4. At week 8, mean change in MADRS total score from baseline was significantly greater for vortioxetine 20 mg/day vs 10 mg/day (difference, À1.03 points; P < .05). Incidence of adverse events was not increased in patients who received vortioxetine 20 mg/day vs 10 mg/day. In flexible-dose studies, dosage was increased to 20 mg/day after 1 week in 48.0% of patients; final dosage was 20 mg/day in 64.3% of patients. Conclusions. Vortioxetine 20 mg is significantly more effective than vortioxetine 10 mg in patients with MDD, with a similar tolerability profile. In flexible-dose studies, almost half of all patients received 20 mg/day after 1 week and two-thirds received 20 mg/day as their final dosage.

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Section: Data Sourcesmentioning

confidence: 99%

“…Meta-Analysis of the Change from Baseline to Week 8 in MADRS Total Score Difference vs Placebo (Full Analysis Set, MMRM) in Fixed-Dose Studies[10][11][12][13][14][15] …”

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confidence: 99%

Vortioxetine 20 mg/day in patients with major depressive disorder: updated analysis of efficacy, safety, and optimal timing of dose adjustment

et al. 2021

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“… 11 In a more recent phase 3 randomized controlled trial enrolling Japanese patients with MDD (CCT-004), a significant improvement from baseline in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was demonstrated at weeks 6 and 8 with vortioxetine 20 mg and at week 8 with vortioxetine 10 mg, each compared with placebo ( P <0.05 for both doses). 12 …”

Section: Introductionmentioning

confidence: 99%

Early Improvement with Vortioxetine Predicts Response and Remission: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan

Inoue¹,

Fujimoto²,

Marumoto³

et al. 2021

NDT

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Aim Several weeks of treatment with an antidepressive agent may be required before efficacy is demonstrated in patients with major depressive disorder. This study investigated the predictive value of early partial improvement with vortioxetine for treatment response and remission. Methods This was a post hoc analysis of an 8-week, randomized, double-blind, placebo-controlled, Phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20–75 years with recurrent major depressive disorder and a Montgomery–Åsberg Depression Rating Scale (MADRS) score of at least 26. The key outcomes were the predictive value of early partial improvement (reduction in MADRS total score of ≥20% from baseline to week 2) with vortioxetine for MADRS response (≥50% decrease in score from baseline) and remission (decrease in score to ≤10) at week 8. Results Relevant data were available for 478 patients; 62/158 patients receiving placebo, 71/162 receiving vortioxetine 10 mg, and 66/158 receiving vortioxetine 20 mg were early improvers. Early improvers receiving vortioxetine (10 mg or 20 mg) were more likely than non-early improvers to achieve a week 8 response (71.2–73.2% vs 29.7–38.0%) or remission (50.7–51.5% vs 17.4–18.7%). Positive predictive values for response and remission with vortioxetine were ~70% and ~50%, respectively; negative predictive values were ~70% and ~80%, respectively. Conclusion Improvement with vortioxetine may be predicted by early partial improvement in MADRS score. Some patients may benefit from longer-term treatment even without early improvement, another finding that may aid clinical decision-making. ClinicalTrials.gov registration for primary study: NCT02389816.

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“…The results of the first two studies (35,36) investigating the effectiveness of vortioxetine for MDD in Japanese patients may have been due to a type II error (i.e., low statistical strength). These two studies (35,36) showed a greater placebo response and a similar drug response when compared with the Inoue et al (37)…”

Section: Efficacy and Tolerability -Short-term Clinical Trialsmentioning

confidence: 74%

“…In another recent eightweek phase III study, patients were randomized to dosage groups of 10 mg (n=165) or 20 mg (n=163) vortioxetine or a placebo (n=161). The findings indicated that vortioxetine at both 10 mg/day and 20 mg/day doses demonstrated strong antidepressant efficacy in Japanese patients with MDD and was well tolerated (37). Kishi et al (38) also conducted a systematic review and meta-analysis to investigate the benefits and effectiveness of vortioxetine in Japanese patients with MDD due to the different results seen in these phase III studies.…”

Section: Efficacy and Tolerability -Short-term Clinical Trialsmentioning

confidence: 99%

Vortioxetine: a comprehensive update on a new-generation antidepressant

Evren¹

2021

Dusunen Adam

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The combined mechanisms of action of new-generation antidepressants may provide greater therapeutic benefits (14).New-generation antidepressants were designed with the goal of optimizing treatment efficacy and tolerability. Vortioxetine is one of the new antidepressants with multimodal activity (10). It is the first mixed serotonin agonist and antagonist antidepressant (7). It has been approved for the treatment of MDD in many countries, including European nations (15) and the United States (16). The antidepressant mechanism of action of vortioxetine combines serotonin transporter (5-HTT) inhibition and direct modulation of serotonin receptor activity; it is a 5-HT1A receptor agonist; a 5-HT1B receptor partial agonist; a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist; and a 5-HTT inhibitor (14,17,18). These additional serotonin receptor targets distinguish vortioxetine from other SSRIs and SNRIs, and this activity may provide unique clinical benefits for symptomatic recovery in MDD patients ( 7). Vortioxetine increases the extracellular concentration of various neurotransmitters, such as dopamine, histamine, noradrenaline, and acetylcholine, in addition to providing a regulatory effect on serotonin receptors and 5-HTT (14,18). The serotonin system has a positive effect on mood, affect, and cognition. Vortioxetine also modulates key neurotransmitters involved in cognitive regulation, such as glutamate, acetylcholine, histamine, dopamine, and noradrenaline (17). Dose and PharmacokineticsVortioxetine is available in 5-, 10-, and 20-mg tablets. Vortioxetine was found to be less effective at low doses of 2.5-5 mg, while a dose range of 5-20 mg is effective (17). The maximum dose of 20 mg vortioxetine has demonstrated a better clinical response than lower doses (19)(20)(21)(22). However, the 20-mg dose has also been associated with a higher risk of side effects ( 14). An initial 10-mg dose once a day may be increased to 20 mg according to tolerability and clinical response (14). The pharmacokinetics of vortioxetine are linear and dose-proportional (23). Since the binding rate of vortioxetine to plasma proteins is 80-90%, it has a wide distribution volume (steady-state distribution volume of approximately 2600 L) (14,23). It has been reported that vortioxetine at higher doses (20 mg) was significantly superior to a placebo ( 14). It takes 3-16

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Randomized, double‐blind, placebo‐controlled study to assess the efficacy and safety of vortioxetine in Japanese patients with major depressive disorder

Cited by 31 publications

References 37 publications

Vortioxetine 20 mg/day in patients with major depressive disorder: updated analysis of efficacy, safety, and optimal timing of dose adjustment

Vortioxetine 20 mg/day in patients with major depressive disorder: updated analysis of efficacy, safety, and optimal timing of dose adjustment

Early Improvement with Vortioxetine Predicts Response and Remission: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan

Vortioxetine: a comprehensive update on a new-generation antidepressant

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