Cost-effectiveness of abobotulinumtoxinA plus best supportive care compared with best supportive care alone for early treatment of adult lower limb spasticity following an acute event.

OBJECTIVES: Spasticity is an incurable chronic condition, and patients with spasticity frequently experience symptoms such as muscle stiffness, restricted mobility, fatigue, spasms, and pain. The study objective was to assess the cost-effectiveness of abobotulinumtoxinA plus best supportive care compared with best supportive care alone for the early treatment of adult lower limb spasticity following an acute event (e.g. stroke or traumatic brain injury), from an Australian payer perspective. METHODS: Using clinical data from published pivotal trials, an economic model based on a Markov model was developed to capture changes in treatment costs, healthcare resource use costs, functional outcomes, and health-related quality of life over a lifetime horizon. Scenario analyses and a probabilistic sensitivity analysis were conducted to explore the uncertainty in the model parameters and assumptions used in the base case. RESULTS: AbobotulinumtoxinA plus best supportive care was cost-effective versus best supportive care, yielding an incremental cost-effectiveness ratio of $35,721 per quality-adjusted life year gained. Sensitivity analyses confirm the robustness of the base case, with most results remaining below the commonly acceptable cost-effectiveness willingness-to-pay threshold of $75,000 per quality-adjusted life year for cost-effectiveness in Australia. Inputs and assumptions that produced the top four highest incremental cost-effectiveness ratios include the application of different health resource utilisation source, short time horizon, unweighted regression analyses to determine regression probabilities, and no stopping rule. AbobotulinumtoxinA plus best supportive care has a 74% probability of being cost-effective compared with best supportive care alone at the willingness to pay threshold. CONCLUSION: AbobotulinumtoxinA plus best supportive care treatment is cost-effective in Australia for the management of adult lower limb spasticity in patients treated within 2 years of an acute event.

Health care resource utilization and costs among patients with spasticity or cervical dystonia.

BACKGROUND: Spasticity and cervical dystonia (CD) are movement disorders with considerable direct and indirect health care cost implications. Although several studies have discussed their clinical impact, few have calculated the economic burden of these disorders. OBJECTIVE: To assess the all-cause health care resource utilization (HCRU) and costs in adults and children with spasticity or CD. METHODS: This retrospective, observational cohort-based study was conducted using administrative insurance claims from the IQVIA PharMetrics Plus database from October 1, 2015, to December 31, 2019. Patients were selected based on International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for first evidence of spasticity (associated with a spasticity etiology) or CD (index date) during the selection window, from April 1, 2016, through December 31, 2018. Cases were stratified into 3 mutually exclusive cohorts: adult patients with spasticity, pediatric patients with spasticity, and patients with CD; those with spasticity who had a history of stroke or cerebral palsy were also evaluated in subcohorts. Patients without evidence of spasticity or CD during the study period were identified as a matched comparator group and were randomly assigned an index date. Patients with spasticity were matched 1:1 to the comparator group based on age, sex, index year, and payer type using descriptive analyses. RESULTS: 215,739 adult patients with spasticity, 29,644 pediatric patients with spasticity, and 9,035 adult patients with CD were identified after matching. Adult patients with spasticity and CD had mean (SD) ages of 48.4 (15.6) years and 48.0 (13.1) years, respectively. Stroke was identified in 31.9% (n = 68,928) of adult patients with spasticity, and cerebral palsy was identified in 11.3% (n = 3,364) of pediatric patients with spasticity. Adult and pediatric patients with spasticity and patients with CD had significantly higher HCRU (including mean number of outpatient, emergency department, and inpatient visits and proportions of patients with prescription fills) and higher mean total health care costs per patient (adult patients with spasticity $29,912 vs $7,464; pediatric patients with spasticity $16,089 vs $2,963; and patients with CD $20,168 vs $7,141) than matched comparators (all P<0.0001). CONCLUSIONS: The management of patients with spasticity or CD results in considerably higher health care expenses. Within managed health care systems, more effective management of spasticity and CD in adult and pediatric patients represents a significant opportunity for cost savings.

A UK Single-Center, Retrospective, Noninterventional Study of Clinical Outcomes and Costs of Two BotulinumtoxinA Treatments for Limb Spasticity.

Service model changes at the North Staffordshire Rehabilitation Centre (UK) included switching spasticity treatment from onabotulinumtoxinA (onaBoNT-A) to abobotulinumtoxinA (aboBoNT-A). This noninterventional, retrospective, longitudinal study (NCT04396704) describes the clinical and economic outcomes in toxin-naive adults with spasticity who received onaBoNT-A (Cohort 1; 2015-2017) or aboBoNT-A (Cohort 2; 2017-2019). Outcomes included Goal Attainment Scale T (GAS-T) score, treatment satisfaction, quality of life (QoL; EQ-5D visual analog scale [VAS] score), and treatment costs. Adverse events were recorded for Cohort 2. Cohort 1 included 60 patients (mean [standard deviation] dose, 206.0 [98.8] U); Cohort 2 included 54 patients (753.7 [457.3] U). Mean (95% confidence interval) GAS-T scores for Cohorts 1 and 2 were 43.1 (39.3-46.9) and 47.8 (43.7-51.9) at Week 6, and 43.2 and 44.3 at Week 12, respectively. In both cohorts most patients were satisfied with treatment. At Week 12, QoL had not changed in Cohort 1 but had improved in Cohort 2 (EQ-5D VAS, -5). Mean estimated per-patient costs (in 2021) for Cohorts 1 and 2 were £315.56 and £249.25, respectively, at Week 6, and £343.20 and £273.21, respectively, at Week 12. Fifteen non-treatment-related serious adverse events and two deaths were recorded. These data may warrant a larger prospective study powered to compare outcomes of aboBoNT-A and onaBoNT-A.

Efficacy of abobotulinumtoxinA versus onabotulinumtoxinA for the treatment of refractory neurogenic detrusor overactivity: a systematic review and indirect treatment comparison.

AIMS: To compare the efficacy and safety of abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) for the treatment of refractory neurogenic detrusor overactivity (NDO), using an indirect treatment comparison (ITC). MATERIALS AND METHODS: A systematic literature review was used to identify randomized controlled trials (RCTs) that evaluated botulinum toxin type A for the treatment of refractory NDO. Treatments were compared using a Bucher ITC approach. Efficacy outcomes were reduction in number of weekly urinary incontinence (UI) episodes at 6, 12, and 24 weeks of follow-up. The safety outcome was the proportion of patients with treatment-emergent urinary tract infections (TE-UTIs) during follow-up. Subgroup/sensitivity analyses were performed to investigate the impact of heterogeneity. RESULTS: Fifteen studies of botulinum toxin type A were identified. Among these, onaBoNT-A 200 U was the only botulinum toxin type A considered an appropriate comparator for aboBoNT-A 600 U and 800 U. As such, six RCTs that evaluated onaBoNT-A or aboBoNT-A were included in the ITC. In base-case analyses, there were no statistically significant differences between aboBoNT-A and onaBoNT-A in terms of UI episodes or TE-UTIs. Numerically, the trend favored aboBoNT-A (either dose) for all endpoints and time points. At 12 and 24 weeks, the difference in reduction of UI episodes per week was considered clinically relevant when comparing aboBoNT-A 800 U with onaBoNT-A 200 U, but not when comparing the lower dose of aboBoNT-A (600 U) with onaBoNT-A 200 U. Results from subgroup/sensitivity analyses were consistent with the base case. LIMITATIONS: Heterogeneity across studies was observed; however, strong consistency of trends across analyses suggests the impact of heterogeneity is low. CONCLUSIONS: There may be potential advantages of aboBoNT-A over onaBoNT-A, in terms of UI reduction, in patients with refractory NDO. More confirmatory studies are needed owing to the sparsity of current evidence.

Neurogenic detrusor overactivity (NDO) is a condition in which the bladder muscle wall is overactive and does not function normally. This can lead to urinary incontinence (i.e. accidental leakage of urine). NDO may also cause urinary tract infections and upper urinary tract damage if it is left untreated or if treatment does not work (i.e. refractory NDO).Botulinum toxin is a treatment that relaxes muscles in patients with refractory NDO, so they have less chance of experiencing urinary incontinence. This study used results from clinical trials to compare two types of botulinum toxin ­ abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) ­ to see if one works better than the other.Clinical trials are experiments to assess how well treatments work by giving different treatments to different patients and observing the results. When there is no clinical trial that compares the two treatments you are interested in, it is possible to combine results from a number of different clinical trials instead. This is known as an indirect treatment comparison.We used an indirect treatment comparison to compare aboBoNT-A and onaBoNT-A for the treatment of refractory NDO. Results showed that aboBoNT-A may be more effective than onaBoNT-A in reducing the frequency of urinary incontinence episodes. On average, patients treated with aboBoNT-A had at least three fewer episodes of urinary incontinence per week than those treated with onaBoNT-A. These results suggest that patients treated with aboBoNT-A could have a better quality of life than those treated with onaBoNT-A.

Modelling Long-Term Outcomes and Risk of Death for Patients with Post-Stroke Spasticity Receiving Abobotulinumtoxina Treatment and Rehabilitation Therapy.

OBJECTIVE: Stroke is associated with a high risk of death and cardiovascular events. Rehabilitation therapy is critical for functional recovery, to reduce hospital readmissions, all-cause and cardiovascular mortality, and stroke recurrence (long-term outcomes). Post-stroke spasticity may prevent effective recovery by restricting mobility. AbobotulinumtoxinA is an adjunctive therapy to physical therapy for post-stroke spasticity, but its long-term effects are unknown. The objective was to model the long-term clinical and economic outcomes of abobotulinumtoxinA for post-stroke spasticity. METHODS: Effects of abobotulinumtoxinA on treating post-stroke spasticity and evidence linking functional outcomes with long-term outcomes were collected in a focused literature review. A model was developed to estimate health benefits on long-term outcomes, direct medical costs, life- and qualityadjusted life-years for abobotulinumtoxinA injections plus rehabilitation therapy compared with rehabilitation therapy alone, from a UK perspective over a 10-year time-period. RESULTS: AbobotulinumtoxinA + rehabilitation therapy led to a risk reduction of 8.8% for all-cause mortality, and an increase of 13% in life-years and 59% in quality-adjusted life-years compared with rehabilitation therapy alone. AbobotulinumtoxinA + rehabilitation therapy was considered cost-effective compared with rehabilitation therapy alone (incremental cost-effectiveness ratio: £24,602). CONCLUSION: AbobotulinumtoxinA + rehabilitation therapy may improve long-term outcomes, including post-stroke survival, while being cost-effective for the treatment of post-stroke spasticity.

The cost-effectiveness of abobotulinumtoxinA (Dysport) and onabotulinumtoxinA (Botox) for managing spasticity of the upper and lower limbs, and cervical dystonia.

OBJECTIVE: To evaluate the costs and benefits associated with the use of abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) for lower limb spasticity in children, upper and lower limb spasticity in adults, and cervical dystonia in adults. METHODS: This pharmacoeconomic analysis compared aboBoNT-A with onaBoNT-A. A decision tree model with a 1-year time horizon was conducted from a UK National Health Service (NHS) perspective using data from a variety of sources: randomized controlled trials (RCTs), network meta-analyses (NMAs), observational studies, and a physician survey investigating treatment patterns and resource utilization. Four patient populations were included: pediatric patients with lower limb spasticity (PLL), and adults with upper limb spasticity (AUL), lower limb spasticity (ALL), and cervical dystonia (CD). Outcomes included costs, quality-adjusted life years (QALYs) gained, cost per responder, and incremental cost per QALY gained. The effectiveness of each treatment was evaluated as a response to treatment. The base case assumption was that all patients in the model continued to receive botulinum toxin type A (BoNT-A) treatments at regular intervals regardless of treatment response status. Scenario analysis evaluated the impact of discontinuing BoNT-A for patients without a response to the first injection. RESULTS: The model found that aboBoNT-A resulted in greater quality-of-life and lower costs compared with onaBoNT-A for the management of spasticity and CD in all included indications. Across populations, cost savings ranged from £304 to £3,963 and QALYs gained ranged from 0.010 to 0.02 over a 1-year time horizon. Results were robust to scenario analyses and were driven by the impact of treatment response on health-related quality-of-life. CONCLUSIONS: AboBoNT-A was associated with higher treatment response, improved quality-of-life, and reduced costs in spasticity and CD versus onaBoNT-A. These findings could help deliver more effective and efficient healthcare in the NHS.

The objective of this study was to compare the costs and health outcomes associated with abobotulinumtoxinA (aboBoNT-A; Dysport) and onabotulinumtoxinA (onaBoNT-A; Botox) for treating children and adults with a variety of conditions related to limb spasticity and cervical dystonia. Therapies such as aboBoNT-A and onaBoNT-A have been shown to reduce spasticity, deformity, pain, and cervical dystonia symptoms. They can also improve function, movement, and self-care abilities. We estimated the treatment costs for patients with spasticity and patients with cervical dystonia receiving aboBoNT-A and onaBoNT-A in the UK. We also estimated other health-related costs that patients were expected to incur while receiving these treatments, as well as their quality of life.For each indication (spasticity in the upper and lower limbs in adults and children, cervical dystonia in adults), research studies were identified to estimate the likelihood of patient response for aboBoNT-A and onaBoNT-A. Survey studies were assessed to understand use of health services and costs for patients who respond to therapy vs. those who do not. We estimated total costs over one year and expected quality of life for patients. Costs included the costs of aboBoNT-A and onaBoNT-A treatments, as well as other health services.In all identified studies, the likelihood of response was higher for aboBoNT-A than for onaBoNT-A. This was associated with reduced need for other health services (and therefore lower costs), and better quality of life for patients receiving aboBoNT-A. In addition, the cost per year of aboBoNT-A treatment was lower than onaBoNT-A treatment for all indications. Therefore, treatment with aboBoNT-A was consistently associated with lower costs and better quality of life. This outcome is referred to as "economically dominant," meaning that from a health economic perspective, aboBoNT-A would be preferred to onaBoNT-A for treating patients with spasticity or cervical dystonia.

Cost-effectiveness of vortioxetine compared with levomilnacipran and vilazodone in patients with major depressive disorder switching from an initial antidepressant.

Introduction: Many patients with major depressive disorder (MDD) do not achieve remission with their first antidepressant (AD), resulting in a high burden due to treatment failure. Vortioxetine is a valid treatment option for patients with MDD only partially responding to their first AD. Characterization of vortioxetine's potential benefits versus other approved treatments is important. Areas covered: The cost-effectiveness of vortioxetine, including cognitive outcomes, was modeled in comparison with levomilnacipran and vilazodone for patients switched to these medications after inadequate responses to a first AD. Expert opinion: Vortioxetine was associated with incremental quality-adjusted life-year (QALY) gains versus levomilnacipran (0.008) or vilazodone (0.009). Vortioxetine was dominant versus levomilnacipran and cost-effective versus vilazodone (incremental cost-effectiveness ratio [ICER],33,829 USD/QALY). In sensitivity analyses using residual cognitive dysfunction rates (vortioxetine, 49%; levomilnacipran, 58%, and vilazodone, 64%), incremental QALY gains for vortioxetine versus levomilnacipran (0.0085) or vilazodone (0.0109) were found. Vortioxetine remained dominant versus levomilnacipran and cost-effective versus vilazodone (ICER, 27,633 USD/QALY). ICER reduction was found with cognition outcomes inclusion. This model provides additional support for considering vortioxetine for patients requiring a switch of MDD treatments, although its conclusions are limited by the data available for inclusion. Additional research and real-world trials are needed to confirm the findings.

Cost effectiveness and impact on quality of life of abobotulinumtoxinA and onabotulinumtoxinA in the treatment of children with lower limb spasticity in Canada.

Background: Injectable botulinum neurotoxins are a mainstay of treatment for pediatric spasticity. AbobotulinumtoxinA and onabotulinumtoxinA are both injectable toxin therapies used to treat pediatric lower limb (PLL) spasticity in Canada. The objective of this study was to assess the cost-effectiveness of abobotulinumtoxinA vs. onabotulinumtoxinA in the treatment of PLL spasticity in Canada.Methods: A probabilistic Markov cohort model with a 2-year time horizon was developed, with health states defined by response to therapy, as characterized by the goal attainment scale (GAS). Based on randomized controlled trial evidence, response to therapy was similar or higher for abobotulinumtoxinA relative to onabotulinumtoxinA; uncertainty was incorporated into model parameters, however, as the two therapies have not been compared head-to-head. Canadian resource use and cost data were incorporated.Results: In the base case, abobotulinumtoxinA generated 1.48 quality-adjusted life years over the model time horizon, compared to 1.47 for onabotulinumtoxinA. AbobotulinumtoxinA was associated with cost savings of $123 CAD, reflecting lower costs in both medication acquisition and health services. The estimated improvement to quality of life and reduced costs result in an estimate of economic dominance for abobotulinumtoxinA over onabotulinumtoxinA. This dominant result persisted across probabilistic and scenario analyses.Key points for decision makersBased on a review of available clinical evidence, abobotulinumtoxinA was found to have significant and/or numerical efficacy benefits to onabotulinumtoxinA on functional outcomes (Goal Attainment Scale) and tone (Modified Ashworth Scale) and in the treatment of pediatric lower limb spasticityIn this cost-effectiveness analysis, abobotulinumtoxinA was found to be associated with greater quality-adjusted life years and lower costs than onabotulinumtoxinA (economically dominant)A limitation of this analysis was the uncertainty around key parameters. Specifically, the lack of head-to-head comparison data for the two therapies, and variable data regarding likely onabotulinumtoxinA dosing in PLL in clinical practice. However, across a range of plausible scenarios, the economic dominant result remained.

Botulinum Toxins Type A (Bont-A) in the Management of Lower Limb Spasticity in Children: A Systematic Literature Review and Bayesian Network Meta-analysis.

BACKGROUND: Botulinum neurotoxins type A (BoNT-As) are used in pediatric lower limb spasticity, which affects more than 2.5 million children worldwide. Botulinum neurotoxins type-A improve active function and delay musculoskeletal complications. The objective of this analysis was to evaluate the efficacy and safety of abobotulinumtoxinA versus other botulinum neurotoxins type A in pediatric spasticity, in the absence of head-to-head evidence. METHODS: A systematic literature review was conducted to identify relevant randomized controlled trials. The evidence base was synthesized with Bayesian network meta-analyses. Outcomes analyzed included Modified Ashworth Scale, Tardieu Scale (TS) spasticity grade, and Goal Attainment Scale (standard mean difference only) at 12 weeks postinjection, and adverse events occurring during study periods. RESULTS: Thirty-eight studies were identified, 10 of which met inclusion criteria for quantitative synthesis. On Modified Ashworth Scale, abobotulinumtoxinA 15 U/kg/leg was significantly more efficacious than onabotulinumtoxinA 4 U/kg/leg (-0.99 [-1.34, -0.64]) and onabotulinumtoxinA 4 U/kg/leg+casting (-0.81 [-1.16, -0.46]) and numerically better than onabotulinumtoxinA 8 U/kg (-0.40 [-0.67, -0.14]). AbobotulinumtoxinA 10 U/kg/leg was significantly more efficacious than onabotulinumtoxinA 4 U/kg/leg (±casting). On Goal Attainment Scale, abobotulinumtoxinA 15 U/kg/leg and 10 U/kg/leg were significantly more efficacious than onabotulinumtoxinA 12 U/kg/leg. On Tardieu Scale spasticity grade, abobotulinumtoxinA was comparable to other treatments. AbobotulinumtoxinA demonstrated adverse event rates comparable to all doses of onabotulinumtoxinA. CONCLUSIONS: In pediatric lower limb spasticity, abobotulinumtoxinA offered significant or numerical efficacy advantages on tone (Modified Ashworth Scale) and functional outcomes (Goal Attainment Scale), and comparable efficacy on Tardieu Scale spasticity grade. AbobotulinumtoxinA was comparable to onabotulinumtoxinA on tolerability. Results should be interpreted in the context of heterogeneity and sparsity of the evidence base.

Psychometric validation of the Perceived Deficits Questionnaire-Depression (PDQ-D) instrument in US and UK respondents with major depressive disorder.

BACKGROUND: Although depression and cognitive dysfunction are connected, limited tools exist to capture the patient's perspective on cognitive dysfunction and its impact on major depressive disorder (MDD). We report results of a psychometric validation of the Perceived Deficits Questionnaire-Depression (PDQ-D), a self-report measure of cognitive dysfunction for use in MDD. METHODS: A non-interventional, prospective, panel-recruited, online survey was conducted using the PDQ-D in adults with and without MDD in the US and UK. Respondents were assessed at baseline and after 6 weeks (MDD only) (baseline: US n=418, UK n=437, 49% MDD; follow-up: US n=169, UK n=153, all MDD). The criterion measures included: Medical Outcomes Study Cognitive Functioning Scale-Revised-acute form (MOS COG-R), Patient Health Questionnaire-9 (PHQ-9), Patient Global Impression of Severity scale (PGI-Severity), Sheehan Disability Scale (SDS), Work Productivity and Activity Impairment Questionnaire: Specific-Health Problem (WPAI:SHP), and modified Lam Employment Absence and Productivity Scale (LEAPS). US and UK data were analyzed separately. RESULTS: Internal consistency was high for PDQ-D total scale and four subscales (Cronbach's alpha 0.81-0.96). Convergent validity was good, with strong concordance with MOS COG-R and moderate/small correlations with PHQ-9, SDS, WPAI:SHP, LEAPS, and PGI-Severity. Significant differences (all P<0.001) existed for all PDQ-D subscale and total scores between MDD/non-MDD samples. The PDQ-D was responsive to changes in depression symptom severity. Confirmatory factor analysis supported scoring of a global overall scale for perceived cognitive dysfunction. CONCLUSION: The PDQ-D provides a reliable and valid measure of subjective cognitive dysfunction in patients with MDD.

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

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.

BACKGROUND: 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). METHODS: Data from nine short-term (6/8 weeks) pivotal studies that included patient functioning assessments were included in this random-effects meta-analysis, which used aggregated study-level data for all therapeutic vortioxetine doses and a mixed-effect model for repeated measures using the full analysis set. RESULTS: A total of 4,216 patients received ≥1 dose of study treatment (1,522 placebo, 2,694 vortioxetine 5-20 mg/day). At study end, the meta-analysis showed improvement for vortioxetine versus placebo (n = 911) in SDS total score (vortioxetine 5 mg, n = 564, change from baseline versus placebo [Δ] -0.24, p = NS; 10 mg, n = 445, Δ -1.68, p ≤ .001; 15 mg, n = 204, Δ -0.91, p = NS; 20 mg, n = 340, Δ -1.94, p ≤ .01). Functional remission (SDS total score ≤6) was observed with vortioxetine 10 mg (n = 170/573; odds ratio [OR] relative to placebo 1.7, p < .001) and 20 mg (n = 144/447; OR 1.6, p < .05), but not 5 mg (n = 207/757; OR 1.1, p = NS) or 15 mg (n = 92/295; OR 1.3, p = NS). CONCLUSION: Vortioxetine 5-20 mg for 6/8 weeks improved overall patient functioning in patients with MDD. Relative to placebo, vortioxetine 10 and 20 mg demonstrated significant improvement in SDS total score and functional remission.

The impact of antidepressant treatments on family functioning in adults with major depressive disorder: a post hoc comparison of vortioxetine and agomelatine.

OBJECTIVE: There is limited research on the impact of antidepressant treatment on family functioning. This study examines the impact of vortioxetine and agomelatine on family functioning using the Depression and Family Functioning Scale (DFFS). METHODS: The DFFS was included in REVIVE, a randomized, double-blind study of adults with major depressive disorder with inadequate response to antidepressant treatment who switched to vortioxetine or agomelatine. The prespecified DFFS analyses were performed using change from baseline to weeks 8 and 12, analyzed by mixed models for repeated measurements by treatment groups. Post hoc analyses compared DFFS scores for remitters and nonremitters. Patients were stratified into quartiles using DFFS scores, and scores on other clinical outcome assessments were compared. RESULTS: Sizeable improvements in DFFS scores were observed from baseline to week 8 (-10.8, -7.9 for vortioxetine and agomelatine, respectively), with further improvements at week 12 (-13.5, -11.0). Vortioxetine (n = 189) was superior to agomelatine (n = 187) by 2.9 DFFS points at week 8 (p < .01) and 2.5 points at week 12 (p < .05), and DFFS item-level improvements were also significantly greater for vortioxetine for 8 of 15 DFFS items at week 8 and 7 items at week 12. At week 8, remitters (n = 142) and nonremitters (n = 233) differed by 11 DFFS points; at week 12, remitters (n = 183) and nonremitters (n = 121) differed by almost 12 DFFS points. Patients stratified into baseline DFFS quartiles showed trends on clinical outcomes such that better family functioning was associated with better functional status and depressive symptoms. CONCLUSIONS: Vortioxetine was significantly superior to agomelatine in terms of family functioning and partner relationships, as well as social functioning, health status, and depression symptoms at weeks 8 and 12. Depressed patients with impaired family functioning showed worse overall functioning, health status, and depression symptoms, suggesting that more attention should be given to family functioning of depressed patients.

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

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.

Patient-centered assessment of cognitive symptoms of depression.

OBJECTIVE: To identify and explore concepts important to patients with cognitive symptoms of major depressive disorder (MDD) and adapt an existing patient-reported outcome (PRO) measure to assess these symptoms. METHODS: Four focus groups were conducted with MDD patients (n = 33) to elicit relevant concepts and determine whether one of several PRO scales could be used to assess cognitive symptoms of depression. Following selection and minor modification of the Perceived Deficits Questionnaire (PDQ), cognitive debriefing interviews were conducted with additional patients (n = 17) to further refine and adapt this measure for use in MDD. Minor revisions based on patient input yielded the PDQ for Depression (PDQ-D). RESULTS: Focus group participants reported a variety of cognitive symptoms that were classified into 7 general categories: lack of focus and clear thought, memory problems, difficulty with lexical access, difficulty with divided attention, difficulty with decision making, difficulty thinking quickly, and difficulty learning new things. Limitations in work productivity were the most commonly reported impacts of cognitive symptoms. While suggesting a few modifications, focus group participants reacted positively to the PDQ based on the breadth, specificity, and relevance of the items. Cognitive debriefing participants indicated that the modified PDQ items were generally easy to understand and relevant to their experiences with MDD. CONCLUSION: Because cognitive symptoms are burdensome to patients with MDD, their assessment is important to optimize treatment outcomes. The PDQ-D has the potential to supplement existing assessment methods, providing unique information important for both comprehensive evaluation of individuals with MDD and evaluation of new treatments.

Psychometric validation of the depression and family functioning scale.

OBJECTIVE: A new patient-reported outcome (PRO) measure developed to assess the impact of major depressive disorder (MDD) on partner and family interactions and quality of relationships, the Depression and Family Functioning Scale (DFFS), was analyzed to establish its reliability, validity, and responsiveness. METHODS: Data from a multi-center, prospective, 2-year observational study were analyzed to assess the psychometric properties of the DFFS in patients with MDD (nBaseline = 478; nMonth2 = 433). Measures administered to assess validity included the Sheehan Disability Scale (SDS), Arizona Sexual Experiences Scale (ASEX) and Short Form Health Survey-12 (SF-12). Reliability (Cronbach's alphas and intra-class correlations), construct validity (factor analysis and correlations), discriminating ability (analyses of variance), and responsiveness (standardized effect size estimates) were evaluated. RESULTS: Principal components analyses indicated a single underlying dimension, confirmed by highly satisfactory Cronbach's alphas (αBaseline = 0.85, αMonth2 = 0.89). The DFFS demonstrated satisfactory test-re-test reliability in patients with the same SDS family life/home responsibilities ratings at baseline and month 2 (intraclass correlation = 0.75). Correlations with other measures showed convergent and divergent validity; e.g., the DFFS correlated better with SF-12 mental component scores (rBaseline = -0.35, rMonth2 = -0.49) than with SF-12 physical component scores (rBaseline = -0.05, rMonth2 = -0.31). Hypothesis tests were generally as predicted; many were statistically significant, substantiating DFFS discriminating ability. Standardized effect size estimates of responsiveness ranged from 0.44-0.84, demonstrating that the items were capable of detecting change. CONCLUSIONS: The psychometric analyses support the reliability, validity, and responsiveness of the DFFS and its usefulness for assessing the impact of depression on family functioning. The DFFS can potentially provide important information not captured in clinical practice and facilitate more comprehensive evaluation of MDD treatments.

The effect of vortioxetine on health-related quality of life in patients with major depressive disorder.

PURPOSE: Major depressive disorder (MDD) has detrimental effects on health-related quality of life (HRQoL). We describe the effect of vortioxetine on HRQoL in MDD patients by using patient-reported outcome instruments. METHODS: HRQoL was evaluated in 5 short-term (6-8 weeks), randomized studies of vortioxetine (5-20 mg/d; n = 2155) versus placebo (n = 1316) in adults with MDD by using the 36-item Short-Form Health Survey (SF-36), the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, the EuroQol 5-Dimension Questionnaire (EQ-5D), and the 12-item Health Status Questionnaire in 1 study in elderly patients. Only patients receiving the approved doses of vortioxetine 5, 10, 15, or 20 mg/d were included in the analysis. A random effects meta-analysis was performed on the 4 adult MDD studies that used the SF-36. A within-studies mixed model for repeated measures analysis based on the full analysis set (FAS) was used unless otherwise specified. Standardized effect size (SES) was calculated to reflect clinical relevance, based on a Cohen's d of 0.2. FINDINGS: Vortioxetine produced significantly better results compared with placebo in the SF-36 mental component summary score (5 mg: 2.6, P = 0.001, SES of 0.22, n = 604; 10 mg: 4.8, P < 0.001, SES of 0.42, n = 328) and 4 domain scores (vitality, social functioning, role emotional, and mental health). Vortioxetine was also significantly better in the EuroQoL-5 Dimension Questionnaire Health State score (10 mg: 7.5, P < 0.05, SES of 0.33, n = 86) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form total score (15 mg: 3.3, P < 0.01, SES of 0.38, n = 127; 20 mg: 4.5, P < 0.0001, SES of 0.52, n = 134) (FAS, last-observation-carried-forward). In the study of elderly patients, vortioxetine 5 mg (n = 136) improved 12-item Health Status Questionnaire scores significantly more than placebo (n = 148) for the domains of health perception (10.4, P < 0.0001, SES of 0.54), mental health (7.9, P < 0.001, SES of 0.44), and energy (6.4, P < 0.05, SES of 0.28) (FAS, mixed model for repeated measures). IMPLICATIONS: Vortioxetine yielded significant, meaningful HRQoL improvements in 6 MDD studies of 6 to 8 weeks' duration.

Challenges in measuring and valuing productivity costs, and their relevance in mood disorders.

Lost productivity is often excluded from economic evaluations, which may lead to an underestimation of the societal benefits of treatment. However, there are multiple challenges in reliably estimating and reporting productivity losses. This article explores the main challenges, ie, selecting an appropriate valuation method (ie, human capital, friction cost, or multiplier), avoiding double counting, and accounting for equity. It also discusses the use of presenteeism instruments and their application in clinical trials, with a specific focus on their relevance in individuals with mood disorders. Further research and discussion is required on the development of reliable techniques for measuring and valuing productivity changes due to presenteeism.

The use and performance of productivity scales to evaluate presenteeism in mood disorders.

OBJECTIVE: Mood disorders are associated with a high societal cost, mainly due to presenteeism. The objective of this study was to review the use of 10 instruments that rate presenteeism in mood disorders and to provide recommendations regarding the appropriateness of instruments in different study settings. METHODS: A systematic review of the literature was conducted to identify scales used to measure presenteeism, including the World Health Organization Health and Work Performance Questionnaire, the Lam Employment Absence and Productivity Scale, the Sheehan Disability Scale, the Work Limitation Questionnaire, and Work Productivity and Activity Impairment questionnaire. Study characteristics and major results (by symptom level, by treatment arm, correlation to other scales, and use of monetization) were data extracted. RESULTS: Twenty-nine studies were identified. The Sheehan Disability Scale, the Work Limitation Questionnaire, and Health and Work Performance Questionnaire were the most commonly used instruments. The majority (60%) of scales demonstrated higher presenteeism in individuals with mood disorders than in individuals without. The Lam Employment Absence and Productivity Scale, the Sheehan Disability Scale, and the Work Limitation Questionnaire showed that presenteeism increased with increasing severity of disease. Few studies reported results on presenteeism by treatment, with only small between-treatment differences observed. Good correlations between presenteeism instruments and clinical or quality-of-life scales were reported. Three studies converted results from presenteeism scales into monetary units. CONCLUSIONS: Limited experiential evidence exists comparing the performance of presenteeism scales in mood disorders. Therefore, recommendations for inclusion of a presenteeism tool must be driven by instrument properties (ease of administration, amenability to monetization) and the study type. Future research should focus on the responsiveness of the instrument and on how mood disorders impact self-reported assessment.

Cost-effectiveness evaluation in Sweden of escitalopram compared with venlafaxine extended-release as first-line treatment in major depressive disorder.

OBJECTIVES: Major depressive disorder (MDD) is a major public health concern associated with a high burden to society, the health-care system, and patients and an estimated cost of €3.5 billion in Sweden. The objective of this study was to assess the cost-effectiveness of escitalopram versus generic venlafaxine extended-release (XR) in MDD, accounting for the full clinical profile of each, adopting the Swedish societal perspective, and identifying major cost drivers. METHODS: Cost-effectiveness of escitalopram versus venlafaxine XR was analyzed over a 6-month time frame, on the basis of a decision tree, for patients with MDD seeking primary care treatment in Sweden. Effectiveness outcomes for the model were quality-adjusted life-years and probability of sustained remission after acute treatment (first 8 weeks) and sustained for 6 months. Cost outcomes included direct treatment costs and indirect costs associated with sick leave. RESULTS: Compared with generic venlafaxine XR, escitalopram was less costly and more effective in terms of quality-adjusted life-years (expected gain 0.00865) and expected 6-month sustained remission probability (incremental gain 0.0374). The better tolerability profile of escitalopram contributed to higher expected quality-adjusted life-years and lower health-care resource utilization in terms of pharmacological treatment of adverse events (though only a minor component of treatment costs). Expected per-patient saving was €169.15 for escitalopram versus venlafaxine. Cost from sick leave constituted about 85% of total costs. CONCLUSIONS: Escitalopram was estimated as more effective and cost saving than generic venlafaxine XR in first-line MDD treatment in Sweden, driven by the effectiveness and tolerability advantages of escitalopram. The study findings are robust and in line with similar pharmacoeconomic analyses.