M. Brignone

Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies

Abstract Introduction: Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012). Methods: We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action. To ensure study comparability, only experimental drug and placebo arms from placebo-controlled registration studies were included in primary analyses. The main outcomes were efficacy (standardized mean difference in change from baseline to 2 months on primary endpoint [MADRS/HAM-D]), and tolerability (withdrawal rate due to adverse events). Results: For efficacy, estimates of treatment effect (negative estimates favor vortioxetine) for vortioxetine versus comparators were: agomelatine, −0.16 (p = 0.11); desvenlafaxine, 0.03 (p = 0.80); duloxetine, 0.09 (p = 0.42); escitalopram, −0.05 (p = 0.70); sertraline, −0.04 (p = 0.83); venlafaxine IR/XR, 0.12 (p = 0.33); and vilazodone, −0.25 (p = 0.11). For tolerability, all but one combination was numerically in favor of vortioxetine (odds ratio < 1), although not all differences were statistically significant: agomelatine, 1.77 (p = 0.03); desvenlafaxine, 0.58 (p = 0.04); duloxetine, 0.75 (p = 0.26); escitalopram, 0.67 (p = 0.28); sertraline, 0.30 (p = 0.01); venlafaxine, 0.47 (p = 0.01); and vilazodone, 0.64 (p = 0.18). Sensitivity analyses did not significantly alter antidepressant effect estimates or relative ranking. Conclusion: These meta-regression data show that vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD. Alternative methods like mixed-treatment comparison and inclusion of all randomized studies and active reference arms may provide complementary information to this analysis (more evidence but also more heterogeneity). Key messages: Indirect comparisons based on registration studies allow a useful comparison between a recently approved antidepressant and an approved drug. Vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D assessments) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD.

Efficacy and tolerability of switching therapy to vortioxetine versus other antidepressants in patients with major depressive disorder

Abstract Objectives: To assess the relative efficacy and tolerability of vortioxetine against different antidepressant monotherapies in patients with major depressive disorder (MDD) with inadequate response to selective serotonin reuptake inhibitor (SSRI) or serotonin–norepinephrine reuptake inhibitor (SNRI) therapy. Methods: A systematic search was conducted for monotherapy studies in patients with MDD with inadequate response to first-line therapy. Treatments included SSRIs, SNRIs, and other antidepressants. Identified studies underwent a three-stage screening/data extraction process and critical appraisal. Adjusted indirect treatment comparisons (ITCs) on systematic literature review outputs were made using Bucher’s method, comparing remission rates and withdrawal rates due to adverse events (AEs). Results: Of 27 studies meeting the inclusion criteria, a few studies were of high quality according to the National Institute of Health and Care Excellence checklist. Three studies contributed to an evidence network for quantitative assessment comparing vortioxetine with agomelatine, sertraline, venlafaxine XR, and bupropion SR. Vortioxetine had a statistically significantly higher remission rate than agomelatine (risk difference [RD]: −11.0% [95% CI: −19.4; −2.6]), and numerically higher remission rates than sertraline (RD: −14.4% [95% CI: −29.9; 1.1]), venlafaxine (RD: −7.20% [95% CI: −24.3; 9.9]), and bupropion (RD: −10.70% [95% CI: −27.8; 6.4]). Withdrawal rates due to AEs were statistically significantly lower for vortioxetine than sertraline (RD: 12.1% [95% CI: 3.1; 21.1]), venlafaxine XR (RD: 12.3% [95% CI: 0.8; 23.8]), and bupropion SR (RD: 18.3% [95% CI: 6.4; 30.1]). Conclusions: The current systematic literature review found a few high quality switch studies assessing monotherapies in patients with MDD with inadequate response to SSRI/SNRIs. ITCs indicated that switching to vortioxetine leads to numerically higher remission rates compared with other antidepressants. Vortioxetine is a well tolerated treatment, showing statistically lower withdrawal rates due to AEs compared with other antidepressants. Vortioxetine is a relevant therapeutic alternative in patients experiencing inadequate response to prior SSRI or SNRI therapy.

Cost-Effectiveness of Escitalopram in Major Depressive Disorder in the Dutch Health Care Setting

OBJECTIVE This study assessed the cost-effectiveness of escitalopram for the treatment of depression in the Netherlands from a societal perspective. METHODS A decision tree model was constructed using decision analytical techniques. Data sources included published literature, clinical trials, official price/tariff lists, national population statistics, and Delphi panel data. The comparators were venlafaxine XR and citalopram. The primary perspective of this health economic evaluation was that of the society in the Netherlands in 2010. The time horizon was 26 weeks. The effectiveness outcomes of the study were quality-adjusted life-years (QALYs). RESULTS Escitalopram was associated with a cost savings per patient of €263 versus venlafaxine XR and €1992 versus citalopram over a period of 26 weeks from a societal perspective. Escitalopram was also associated with a gains QALYs: 0.0062 versus venlafaxine XR and 0.0166 versus citalopram. Escitalopram was dominant over both venlafaxine XR and citalopram. CONCLUSION Based on the findings from this cost-effectiveness analysis, the favorable clinical benefit of escitalopram resulted in a positive health economic benefit in the Netherlands.

Cost-utility analysis of vortioxetine versus agomelatine, bupropion SR, sertraline and venlafaxine XR after treatment switch in major depressive disorder in Finland

ABSTRACT Background: To assess the cost-utility of vortioxetine versus relevant comparators (agomelatine, bupropion SR, sertraline, and venlafaxine XR) in the finnish setting in major depressive disorder (MDD) patients with inadequate response to selective serotonin- /serotonin–norepinephrine reuptake inhibitors. Methods: A one-year analysis was conducted using a decision tree with a Markov state transition component. The health states were remission, relapse and recovery. A Finnish healthcare payer perspective was adopted. Results: Vortioxetine was less costly and more effective versus all comparators in both direct and societal perspectives. Vortioxetine reduced the average annual direct costs by 4% versus venlafaxine XR and 8% versus sertraline. The greater efficacy associated with vortioxetine was translated into a higher percentage of patients in remission and recovery. The model was most sensitive to changes in remission rates at 8 weeks. Conclusion: This cost-utility analysis showed vortioxetine to be a good alternative for MDD patients switching therapy in Finland.

Cost-effectiveness of vortioxetine versus venlafaxine (extended release) in the treatment of major depressive disorder in South Korea

ABSTRACT Objective: To assess the cost-effectiveness of vortioxetine versus venlafaxine XR (extended-release) in major depressive disorder (MDD) patients in South Korea. Methods: A 1-year cost-effectiveness analysis from a limited societal perspective was performed using a combined model consisting of a decision-tree and a Markov model. Patients entered the model when initiating or switching antidepressant treatment following inadequate response to previous treatment. Remission, relapse and recovery were the main health states. Results: Vortioxetine dominated venlafaxine XR, with quality-adjusted life year (QALY) gains of 0.0131 and cost savings of KRW 623,229/year [US

A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder

530/year] from a limited societal perspective. Safety contributed more than efficacy to the incremental QALY gains. More patients were in recovery after initial treatment and after 1 year with vortioxetine (31%, 40%) compared to venlafaxine XR (23%, 36%). Vortioxetine remained dominant in 98% of probabilistic simulations. Conclusion: Vortioxetine dominated venlafaxine XR in South Korea and is a relevant treatment option for MDD patients initiating or switching therapy.

Comparative evaluation of vortioxetine as a switch therapy in patients with major depressive disorder

Abstract Background Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. Methods MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. Results The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. Conclusions This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder.

Pharmacotherapeutic strategies for patients treated for depression in UK primary care: a database analysis

Switching antidepressant therapy is a recommended strategy for depressed patients who neither respond to nor tolerate an initial pharmacotherapy course. This paper reviews the efficacy and tolerability of switching to vortioxetine. All three published studies of patients with major depressive disorder (MDD) switched from SSRI/SNRI therapy to vortioxetine due to lack of efficacy or tolerability were selected. Vortioxetine was evaluated versus agomelatine directly (REVIVE) and versus sertraline, venlafaxine, bupropion, and citalopram in an indirect treatment comparison (ITC) from switch studies retrieved in a literature review. Vortioxetine׳s impact on SSRI-induced treatment-emergent sexual dysfunction (TESD) was assessed directly versus escitalopram (NCT01364649) in stable patients with MDD. Vortioxetine׳s tolerability in the switch population was compared to the overall MDD population. Vortioxetine showed significant benefits over agomelatine on efficacy, functioning, and quality-of-life outcomes, with fewer withdrawals due to adverse events (AEs) (REVIVE). Vortioxetine had numerically higher remission rates versus all therapies included (ITC). Withdrawal rates due to AEs were significantly lower for vortioxetine versus sertraline, venlafaxine, and bupropion, and numerically lower versus citalopram. Switching to vortioxetine was statistically superior to escitalopram in improving TESD (NCT01364649). Tolerability was similar in the switch and overall MDD populations. These findings suggest that vortioxetine is an effective switch therapy for patients with MDD whose response to SSRI/SNRI therapy is inadequate. Vortioxetine was well tolerated and, for patients with a history of TESD, showed significant advantages versus escitalopram. Vortioxetine appears to be a valid option for patients with MDD who have not been effectively treated with first-line pharmacotherapies.

The effect of vortioxetine on overall patient functioning in patients with major depressive disorder

Abstract Objective: To investigate long-term patterns of antidepressant treatment in patients in primary care in the UK, and to assess their healthcare resource use and disease outcomes. Research design and methods: A retrospective longitudinal cohort study was conducted using the Clinical Practice Research Datalink. The study population comprised patients aged ≥18 years with depression receiving a prescription for antidepressant monotherapy between 1 January 2006 and 31 December 2011 with no antidepressants within the preceding 6 months. Recovery was defined by timing of antidepressant prescriptions (≥6 months without treatment). Treatment lines and strategies (switching, combining, augmenting and resuming medication) were analyzed. Healthcare resource use for the different treatment strategies and periods of no therapy was assessed. Results: Data from 123,662 patients (287,564 treatment lines) were analyzed. Switching and resumption of treatment were more frequent than other strategies. Recovery was highest with first-line monotherapy (45% of patients), while as a second-line strategy switching was more successful (43%) than combination or augmentation. In subsequent lines of treatment, switching was associated with successively lower rates of recovery (31% in the third line and 24% from the fourth line onwards). Similar rates were observed for resumption. Healthcare resource use was greater during antidepressant use than treatment-free periods. Augmentation was associated with the highest proportions of patients with a psychiatrist referral, psychologist referral and psychiatric hospitalization. Conclusions: This study provides extensive real-world information on the prescribing patterns and treatment outcomes for a large cohort of patients treated for depression with antidepressants in primary care. Switching is more frequently used than augmentation or combination treatment, with decreasing effectiveness across successive lines. Key limitations of the study were: (i) risk of selection bias due to the use of inclusion criteria based on depression diagnoses recorded by the practitioner; and (ii) reliance on prescribing patterns as proxies for clinical outcomes, such as recovery.

Economic Burden of Major Depressive Disorder (Mdd) in Five European Countries: Description of Resource use by Health State.

The objectives of this meta‐analysis of data from randomized, placebo‐controlled studies were to assess the effect of vortioxetine on overall functioning (primary) and functional remission (secondary) using the Sheehan Disability Scale (SDS) in adults with major depressive disorder (MDD).