Successfully treated patients with vortioxetine versus venlafaxine: a simplified cost-effectiveness analysis based on a head-to-head study in Asian patients with major depressive disorder.

Objective: To compare the rates of successfully treated patients (STPs) with vortioxetine versus venlafaxine in major depressive disorder (MDD), using dual endpoints that combine improvement of mood symptoms with optimal tolerability or functional remission, and conduct a simplified cost-effectiveness analysis.Methods: The 8-week SOLUTION study (NCT01571453) assessed the efficacy and safety of vortioxetine (10 mg/day) versus venlafaxine XR (150 mg/day) in adult Asian patients with MDD. Rates were calculated post-hoc of STP Mood and Tolerability (≥50% reduction from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] total score and no treatment-emergent adverse events) and STP Mood and Functioning (≥50% reduction from baseline in MADRS total score and Sheehan Disability Scale total score ≤6). The incremental costs per STP were assessed using the 2018 pharmacy purchase prices for branded vortioxetine/branded venlafaxine in China as the base case.Results: STP Mood and Tolerability rates were 28.9% for vortioxetine and 19.9% for venlafaxine (p = .028); the corresponding STP Mood and Functioning rates were 28.0% and 23.5% (p = .281). Drug costs for the 8-week treatment period were CN¥1954 for vortioxetine and CN¥700 for venlafaxine. The incremental cost per STP for vortioxetine versus venlafaxine was CN¥13,938 for Mood and Tolerability and CN¥27,876 for Mood and Functioning.Conclusions: Higher rates of dual treatment success were seen with vortioxetine versus venlafaxine. Although vortioxetine was not dominant in the base case, the incremental cost per STP for vortioxetine versus venlafaxine were overall within acceptable ranges. These results support the benefits previously reported with vortioxetine versus other antidepressants in broad efficacy, tolerability profile and cost-effectiveness.

Healthcare Costs and Medication Adherence Among Patients with Fibromyalgia: Combination Medication vs. Duloxetine, Milnacipran, Venlafaxine, and Pregabalin Initiators.

OBJECTIVE: To examine medication adherence and healthcare costs for combination prescription initiators (duloxetine/milnacipran/venlafaxine with pregabalin) vs. monotherapy initiators (duloxetine, milnacipran, venlafaxine, and pregabalin) among patients with fibromyalgia syndrome (FMS). METHODS: Our retrospective cohort study used claims data for the South Carolina Blue Cross Blue Shield State Health Plan (SHP). Patients with FMS ≥ 18 years of age, with prescription initiation from July 1, 2007, through June 30, 2010, and SHP enrollment for 12 months pre- and post-index periods were included (combination: n = 100; pregabalin: n = 665; duloxetine: n = 713; milnacipran: n = 131; venlafaxine: n = 272). Medication adherence measures included high adherence (medication possession ratio ≥ 80%) and total supply days. Healthcare costs comprised direct medical expenditures. Propensity score methods of inverse probability of treatment weights were used to control for selection bias due to differing pre-index characteristics. RESULTS: Odds ratios for high adherence were significantly increased (P < 0.05) among the combination cohort vs. the venlafaxine (2.15), duloxetine (1.39), and pregabalin (2.20) cohorts. Rate ratios for total supply days were significantly higher (P < 0.05) for combination vs. venlafaxine (1.23), duloxetine (1.08), and pregabalin (1.32) cohorts. Expenditures for total health care were significantly higher (P < 0.05) for combination vs. duloxetine ($26,291 vs. $17,190), milnacipran ($33,638 vs. $22,886), and venlafaxine ($26,586 vs. $16,857) cohorts. CONCLUSIONS: Medication adherence was considerably better for combination prescription initiators; however, expenditures for total health care were higher. Still, our findings suggest important clinical benefits with the use of combination prescription therapy, and prospective studies of medication adherence are warranted to examine causal relationships with outcomes not captured by healthcare claims databases.

Cost-Effective Drug Switch Options After Unsuccessful Treatment With an SSRI for Depression.

OBJECTIVE: Multiple treatment options are available for patients who do not respond to initial treatment for major depressive disorder. Previous results show that bupropion, sertraline, and venlafaxine are comparable in terms of therapeutic effectiveness following unsuccessful treatment with citalopram. In this study, we extended these results by incorporating costs of treatment to determine if one option was more cost-effective relative to others. METHODS: In the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) trial, 727 patients were randomly assigned to a switch drug treatment during level 2; 239 (33%) were assigned to bupropion, 238 (33%) to sertraline, and 250 (34%) to venlafaxine. For each study medication, the total costs included the costs of the medication, other concomitant medication and antidepressants, and health care facility utilization. Effectiveness was measured as remission and response. Cost-effectiveness was assessed as net health benefits. Stochastic analysis was performed by using the bootstrapping method. RESULTS: During level 2, mean medication costs were significantly higher for venlafaxine than for bupropion and sertraline ($968, $607, and $703, respectively). There were no significant differences among the switch medications in costs for other medications and health care facility utilization. Although the total costs were significantly different for the three medications (p=.025), none of the pairwise differences between medications were significant. Also, after jointly estimating costs and effects, the analyses found that net health benefits were not significantly different among the three drugs. CONCLUSIONS: After unsuccessful treatment with citalopram, the switch options of bupropion, sertraline, and venlafaxine were not significantly different from each other in terms of cost-effectiveness.

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.

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

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$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.

[Economic evaluation of desvenlafaxine in the treatment of major depressive disorder in Spain]. / Evaluación económica de la desvenlafaxina en el tratamiento de la depresión mayor en España.

INTRODUCTION: The objective of this analysis was to evaluate the clinical and economic value of the use of 50mg-desvenlafaxine compared to the usual care (mix of duloxetine and venlafaxine) in the outpatient treatment of major depressive disorder after first line treatment failure (relapse) in Spain. MATERIALS AND METHODS: A Markov model was used to follow up a cohort of major depressive disorder patients for one year after failure of first-line treatment with a serotonin-specific reuptake inhibitor and estimate outcome measures (percentage remission and depression-free days) and accrued and direct costs incurred during outpatient treatment of major depressive disorder. In order to obtain the efficacy data related to the treatment alternatives, a literature review of clinical trials was performed. A panel of clinical experts validated the use of clinical resources employed in the estimation of economic outcomes together with model assumptions. The analysis was performed in 2014 from the perspective of the National Health System. RESULTS: Due to fewer discontinuations, initiating second line treatment with desvenlafaxine was associated with more depression-free days and a higher percentage of patients in remission versus usual care: 1.7 days and 0.5%, respectively. This was translated into lower drug and events management costs, and an overall cost reduction of €108 for the National Health System. CONCLUSIONS: In patients who have not responded to a first-line serotonin-specific reuptake inhibitor therapy, desvenlafaxine-50mg was clinically similar in effectiveness, but a less costly option, compared with a weighted average of duloxetine and venlafaxine for the second-line treatment of major depressive disorder patients from a payer (National Health System) perspective in Spain.

An Evaluation of Health Service Impacts Consequent to Switching from Brand to Generic Venlafaxine in New Zealand under Conditions of Price Neutrality.

OBJECTIVE: To study the health impact on adult New Zealand patients who switch from originator brand to generic venlafaxine. METHODS: The national pharmacy database was used to select patients using venlafaxine for at least 6 months. Switchers and nonswitchers were identified, and switch behavior was compared for a 12-month follow-up period. Change in health service use following switching was also compared between switchers and nonswitchers including use of the emergency department, hospital, and specialist outpatient services over the same period. RESULTS: Approximately 12% of all originator brand users switched to generic venlafaxine, at least half of whom continued to use the generic throughout the follow-up period to August 1, 2012. Almost 60% of new users of the generic venlafaxine, however, switched to using the originator brand. Aside from a slight reduction in the use of outpatient services among switchers, there were no significant differences in health services use between switchers and nonswitchers for either existing or new venlafaxine users. CONCLUSIONS: Although both products remain fully subsidized and available, there is little incentive for prescribers, pharmacists, or patients to switch to the less expensive generic brand. If savings to the national New Zealand budget are to be realized, additional policy measures should be implemented to minimize incentives for multiple and reverse switching, and prescribers, as key opinion leaders, could take the lead in promoting generics to their patients.

Management of Newer Antidepressant Medications in U.S. Commercial Health Plans.

BACKGROUND: Private health insurance plays a large role in the U.S. health system, including for many individuals with depression. Private insurers have been actively trying to influence pharmaceutical utilization and costs, particularly for newer and costlier medications. The approaches that insurers use may have important effects on patients' access to antidepressant medications. AIMS OF THE STUDY: To report which approaches (e.g., tiered copayments, prior authorization, and step therapy) commercial health plans are employing to manage newer antidepressant medications, and how the use of these approaches has changed since 2003. METHODS: Data are from a nationally representative survey of commercial health plans in 60 market areas regarding alcohol, drug abuse and mental health services in 2010. Responses were obtained from 389 plans (89% response rate), reporting on 925 insurance products. For each of six branded antidepressant medications, respondents were asked whether the plan covered the medication and if so, on what copayment tier, and whether it was subject to prior authorization or step therapy. Measures of management approach were constructed for each medication and for the group of medications. Bivariate and multivariate analyses were used to test for association of the management approach with various health plan characteristics. RESULTS: Less than 1% of health plan products excluded any of the six antidepressants studied. Medications were more likely to be subjected to restrictions if they were newer, more expensive or were reformulations. 55% of products used placement on a high cost-sharing tier (3 or 4) as their only form of restriction for newer branded antidepressants. This proportion was lower than in 2003, when 71% of products took this approach. In addition, only 2% of products left all the newer branded medications unrestricted, down from 25% in 2003. Multivariate analysis indicated that preferred provider organizations were more likely than other product types to use tier 3 or 4 placement. DISCUSSION: We find that U.S. health plans are using a variety of strategies to manage cost and utilization of newer branded antidepressant medications. Plans appear to be finding that approaches other than exclusion are adequate to meet their cost-management goals for newer branded antidepressants, although they have increased their use of administrative restrictions since 2003. Limitations include lack of information about how administrative restrictions were applied in practice, information on only six medications, and some potential for endogeneity bias in the regression analyses. CONCLUSION: This study has documented substantial use of various restrictions on access to newer branded antidepressants in U.S. commercial health plans. Most of these medications had generic equivalents that offered at least some substitutability, reducing access concerns. At the same time, it is worth noting that high copayments and administrative requirements can nonetheless be burdensome for some patients. IMPLICATIONS FOR HEALTH POLICY: Health plans' pharmacy management approaches may concern policymakers less than in the early 2000s, due to the lesser distinctiveness of today's branded medications. This may change depending on future drug introductions. IMPLICATIONS FOR FURTHER RESEARCH: Future research should examine the impact of plans' pharmacy management approaches, using patient-level data.

Influence of the CYP2D6 isoenzyme in patients treated with venlafaxine for major depressive disorder: clinical and economic consequences.

BACKGROUND: Antidepressant drugs are the mainstay of drug therapy for sustained remission of symptoms. However, the clinical results are not encouraging. This lack of response could be due, among other causes, to factors that alter the metabolism of the antidepressant drug. OBJECTIVE: to evaluate the impact of concomitant administration of CYP2D6 inhibitors or substrates on the efficacy, tolerability and costs of patients treated with venlafaxine for major depressive disorder in clinical practice. METHODS: We designed an observational study using the medical records of outpatients. Subjects aged ≥ 18 years who started taking venlafaxine during 2008-2010 were included. Three study groups were considered: no combinations (reference), venlafaxine-substrate, and venlafaxine-inhibitor. The follow-up period was 12 months. The main variables were: demographic data, comorbidity, remission (Hamilton <7), response to treatment, adverse events and costs. The statistical analysis included logistic regression models and ANCOVA, with p values <0.05 considered significant. RESULTS: A total of 1,115 subjects were recruited. The mean age was 61.7 years and 75.1% were female. Approximately 33.3% (95% CI: 30.5 to 36.1) were receiving some kind of drug combination (venlafaxine-substrate: 23.0%, and venlafaxine-inhibitor: 10.3%). Compared with the venlafaxine-substrate and venlafaxine-inhibitor groups, patients not taking concomitant drugs had a better response to therapy (49.1% vs. 39.9% and 34.3%, p<0.01), greater remission of symptoms (59.9% vs. 50.2% and 43.8%, p<0.001), fewer adverse events (1.9% vs. 7.0% and 6.1%, p<0.05) and a lower mean adjusted cost (€2,881.7 vs. €4,963.3 and €7,389.1, p<0.001), respectively. All cost components showed these differences. CONCLUSIONS: The patients treated with venlafaxine alone showed a better response to anti-depressant treatment, greater remission of symptoms, a lower incidence of adverse events and lower healthcare costs.