Utility of eosin Y as a complexing reagent for the determination of citalopram hydrobromide in commercial dosage forms by fluorescence spectrophotometry.

An accurate, selective and sensitive spectrofluorimetric method was developed for the determination of citalopram hydrobromide in commercial dosage forms. The method was based on the formation of a fluorescent ion-pair complex between citalopram hydrobromide and eosin Y in the presence of a disodium hydrogen phosphate/citric acid buffer solution of pH 3.4 that was extractable in dichloromethane. The extracted complex showed fluorescence intensity at λem = 554 nm after excitation at 259 nm. The calibration curve was linear over at concentrations of 2.0-26.0 µg/mL. Under optimized experimental conditions, the proposed method was validated as per ICH guidelines. The effect of common excipients used as additives was tested and the tolerance limit calculated. The limit of detection for the proposed method was 0.121 µg/mL. The proposed method was successfully applied to the determination of citalopram hydrobromide in commercial dosage forms. The results were compared with the reference RP-HPLC method.

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.

Potential cost-effectiveness of therapeutic drug monitoring for depressed patients treated with citalopram.

BACKGROUND: For patients treated with citalopram, it was recently shown that serum concentrations above 50 ng/mL on day 7 of treatment are associated with an improved therapeutic outcome. The aim of this post hoc analysis was to calculate a potential cost-effectiveness of therapeutic drug monitoring (TDM) considering costs for hospitalization, medication, and drug analysis. METHODS: The study included patients with major depression. Weekly measurements of serum concentrations and assessments of psychopathology were conducted. RESULTS: Fifty-five patients were included in this analysis. For patients with high citalopram serum concentrations (>50 ng/mL), the mean duration of hospitalization was 49 ± 20 days, and it was 72 ± 37 days (P = 0.03) in the group with low drug concentrations (<50 ng/mL). Considering daily costs for hospitalization of 250€,;, the potential savings amounted to 5750€,; per patient for the 23 days. Assuming that 11% of the variation of duration of hospitalization per patient were attributed to the serum concentration of the drug, the resulting savings were 633€,; per patient. Considering the officially listed price of 21€,; per TDM assay, total costs for weekly measurements over a period of 10 weeks of hospitalization were 210€,;. In the groups with high and low serum concentrations, daily costs for citalopram medication were 3.00 ± 0.80€,; and 2.42 ± 0.70€,;, respectively (P = 0.002), and the mean number of comedications was nearly identical, that is, 1.87 ± 1.74 and 1.81 ± 1.86 drugs, respectively (P = 0.919). CONCLUSIONS: The data taken together indicate that TDM-guided dosing of citalopram has the potential to be cost effective by reducing the length of hospitalization.

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.

Assessing the comparative-effectiveness of antidepressants commonly prescribed for depression in the US Medicare population.

BACKGROUND: Depression is among the most common chronic illnesses in the US elderly Medicare population, affecting approximately 11.5% of beneficiaries with estimated costs of about USD 65 billion annually. Patients with depression are typically treated with antidepressants - most commonly the Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs vary substantially in their costs, side effect profiles and convenience of use. All these factors might affect medication adherence and subsequently down-stream medical costs. AIMS OF STUDY: To assess the comparative-effectiveness of three antidepressants (escitalopram, citalopram, sertraline) commonly-prescribed for depression in Medicare. METHODS: We used pharmacy and medical claims data for a 5 percent national random sample of Medicare beneficiaries who were diagnosed with depression in 2008 and followed until 12/31/2009. Key measures included drug spending, medication adherence to antidepressants, down-stream non-drug medical costs at three levels: all, psychiatric and depression related costs. Three methods were conducted to test robustness: generalized linear regression (GLM), propensity score matching, and an instrumental variables (IV) approach. For the instrumental variables approach, we used a two-stage residual inclusion model, using geographic variation in the use of the various drugs as instruments. Specifically, we calculated the ratio of the number of individuals who used each drug to the total number of individuals using any antidepressants at the 306 Dartmouth hospital-referral regions. RESULTS: The regression and the propensity score matching method each showed that patients using escitalopram had significantly worse adherence, higher drug costs, and higher medical costs than patients using either citalopram or sertraline. However, our IV analysis yielded different results. While drug costs remained significantly higher for escitalopram patients, we found that escitalopram users had lower non-drug medical spending than patients who used citalopram, which was enough to offset the higher drug costs. The instrumental variables results also suggested that sertraline users had lower non-drug medical costs than citalopram users. The differences between sertraline and escitalopram were not statistically significant for medical spending, but sertraline users had lower drug costs and better adherence than escitalopram users. DISCUSSION: The IV method yielded somewhat different results than the GLM regressions and the propensity score matching methods. Once we controlled for selection bias using the instrumental variables, we found that escitalopram is actually associated with lower medical spending. One interpretation is that the IV approach mitigates selection biases due to unobserved factors that are not controlled in regular regressions. However, one conclusion remains the same: in every model, we found that sertraline was at least as cost-effective as or more cost-effective than the other drugs. LIMITATIONS: Potential unobserved factors affecting the choice of three antidepressants are possible. IMPLICATIONS FOR HEALTH POLICIES: All methods indicated that sertraline is the most cost-effective drug to treat depression. Substantial savings to Medicare could be realized by using more cost-effective antidepressants such as sertraline. IMPLICATIONS FOR FURTHER RESEARCH: Geographic variation in the use of prescription drugs has been underutilized as an instrumental variable in comparative-effectiveness research. Our study demonstrates that it can help to control for selection biases in observational data.

Switching to sertraline or venlafaxine after failure of SSRIs treatment in major depressive disorder: an economic evaluation of the STAR*D trial.

BACKGROUND: Switching to another antidepressant is one of the alternative treatment strategies employed in major depressive disorder (MDD) patients who have no remission despite an adequate trial of an antidepressant. The aim of the present study was to present an economic evaluation of sertraline compared with venlafaxine after unsuccessful treatment for depression with citalopram. MATERIAL AND METHOD: An economic model was constructed in line with the design of the sequenced treatment alternatives to relieve depression (STAR*D) study. MDD patients who did not have a remission with or who had an intolerance to citalopram were randomly assigned to be switched to either sertraline or venlafaxine. Patients who had no remission at the end of the switching treatment phase still continued the antidepressants and received an adjunctive treatment with aripiprazole. The event probabilities were used to derive the transitional probabilities use in the model. The primary model outcome was remission of symptoms and the secondary outcome was quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICEs) were estimated for the costs per unit of effectiveness. Sensitivity analyses were done to assess the effects of model assumptions. RESULTS: The total direct costs per remission were 27,830 Baht for sertraline and 30,147 Baht for venlafaxine. Sertraline had lower total costs per QALY than venlafaxine (34,788 Baht vs. 37,683 Baht). The more cost-effectiveness of sertraline resulted in 7.68% of cost saving. The incremental cost of venlafaxine compared with sertraline was 2,316 Baht per remission gained and 2895 Baht per QALY gained. By varying the remission rate of venlafaxine from 20% to 40%, the sensitivity analysis results in a decrease in total costs of venlafaxine from 31,926 Baht to 24,808 Baht. In addition, incremental cost per remission gained changed from 4096 Baht in favour of sertraline to 3023 Baht in favour of venlafaxine. Similarly, incremental cost per QALY gained changedfrom in favour of sertraline to in favour of venlafaxine. CONCLUSION: Based on the STAR*D trial, the results of the economic study indicate that a switch to sertraline is a cost-effectiveness treatment option compared with a switch to venlafaxine in MDD patients who have no remission or cannot tolerate citalopram.

Treatment persistence & health care costs of adult MDD patients treated with escitalopram vs. citalopram in a medicaid population.

OBJECTIVE: Compare treatment persistence and health care costs of major depressive disorder (MDD) Medicaid patients treated with escitalopram versus citalopram. DESIGN: Retrospective analysis of Medicaid administrative claims data. METHODOLOGY: Analyzed administrative claims data from the Florida Medicaid program (07/2002-06/2006) for patients ages 18-64 years with 21 inpatient claim or 2 independent medical claims for MDD. Outcomes included discontinuation and switching rates and prescription drug, medical, and total health care costs, all-cause and related to mental disorder. Contingency table analysis and survival analysis were used to compare outcomes between treatment groups, using both unadjusted analysis and multivariate analysis adjusting for baseline characteristics. RESULTS: The study included 2,650 patients initiated on escitalopram and 630 patients initiated on citalopram. Patients treated with escitalopram were less likely to discontinue the index drug (63.7% vs. 68.9%, P=0.015) or to switch to another second-generation antidepressant (14.9% vs. 18.4%, P=0.029) over the six months post-index date. Patients treated with escitalopram had $1,014 lower total health care costs (P=0.032) and $519 lower health care costs related to mental disorder (P=0.023). More than half of the total cost difference was attributable to savings in inpatient hospitalizations related to mental disorder ($571, P=0.003) and to outpatient costs ($53, P<0.001). Escitalopram therapy was also associated with $736 lower medical costs related to mental disorder (P=0.009). CONCLUSION: In the Florida Medicaid program, compared to adult MDD patients initiated on citalopram, escitalopram patients have better treatment persistence and lower total health care costs due to any cause and due to mental disorder, mostly driven by lower hospitalization costs related to mental disorder.

Economic impact of therapeutic substitution of a brand selective serotonin reuptake inhibitor with an alternative generic selective serotonin reuptake inhibitor in patients with major depressive disorder.

BACKGROUND: To reduce pharmacy costs, managed care organizations encourage therapeutic substitution from brand to a generic product. However, little is known about whether these cost-containment strategies can also potentially lower total expenditures for payers in treatment of major depressive disorder (MDD). OBJECTIVE: To compare economic outcomes of patients with MDD who were switched from a brand selective serotonin reuptake inhibitor (SSRI) to an alternative generic SSRI for nonmedical reasons versus patients who continued on the brand SSRI. METHODS: Adult MDD patients in the Ingenix Impact Database (2003-2007) were considered "switchers" if they received treatment with a brand SSRI and were later switched to an alternative generic SSRI for nonmedical reasons. Patients who remained on the brand SSRI (nonswitchers) were matched 1:1 with switchers. All-cause, mental health-related, and MDD-related rates of hospitalizations/emergency department (ED) visits and costs over 6 months were compared both descriptively and by using adjusted regression models. A subgroup analysis on patients who were switched from escitalopram (Lexapro) to an alternative generic SSRI was also performed. RESULTS: The study included 4449 matched pairs. Compared with nonswitchers, switchers had higher risk of all-cause, mental health-related, and MDD-related use of hospitalizations/ED visits (OR 1.15, 1.34, and 1.54, respectively; all p < 0.01) and higher risk-adjusted mental health-related and MDD-related medical costs ($219 and $222, respectively; both p < 0.05). Subgroup analysis on escitalopram showed similar results; switchers experienced higher risk of any-cause, mental health-related, and MDD-related use of hospitalizations/ED visits (OR 1.21, 1.41, and 1.53, respectively; all p < 0.01) and higher risk-adjusted MDD-related medical costs ($151; p < 0.05). CONCLUSIONS: Compared with patients who continued on their patented SSRIs, patients who switched to a generic SSRI incurred more resource use of hospitalizations/ED visits and higher MDD-related health-care costs. The effects of therapeutic substitution should be carefully examined, because use of generic alternatives may not be a cost-saving strategy when total health-care costs are considered.

Developing thai economic model to study cost-effectiveness of switching to bupropion compared to combination with bupropion after the failure of an SSRI for major depressive disorder.

OBJECTIVE: To present an economic model and cost-effectiveness estimates of switching to bupropion compared to combination with bupropion after failure of an SSRI for major depressive disorder (MDD). MATERIAL AND METHOD: An economic model was developed to simulate the transitions of Thai outpatients with nonpsychotic MDD who had no remission or could not tolerate the SSRI citalopram and received either sustained-release bupropion monotherapy as switching strategy or sustained-release bupropion plus citalopram as combination strategy. Clinical data were obtained form 2 trials of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The four event probabilities: remission rates, rates of non-remission, discontinuation rates due to intolerance, and incidence of serious adverse events were estimated. Direct costs included drug cost, hospitalizations, and electroconvulsive therapy (ECT). The primary outcome considered in the model was a remission of symptoms. Outputs were measured in terms of costs per remission and costs per quality-adjusted life-years (QALYs). RESULTS: In the base-case analysis, the total direct costs with a bupropion switch were 22,937 THB per remission and 29,346 THB per remission with a bupropion combination. Compared with combination option, switching to bupropion also had lower total cost per QALY (28,672 THB vs. 36,682 THB) and had cost saving of 21.8%. The incremental cost-effectiveness of the combination regimen compared with the switching regimen was 6,409 THB per remission gained and 8,011 THB per QALY gained. In a sensitivity analysis, combination strategy dominated switching strategy if the value of the transitional probability of remission changed to a value of greater than 0.547. CONCLUSION: The economic model indicated that treatment of MDD patients who fail to achieve remission from an SSRI with a switch to bupropion is a cost-effectiveness treatment option compared with a combination of SSRI with bupropion.

Generic escitalopram initiation and substitution among Medicare beneficiaries: A new user cohort study.

OBJECTIVES: To examine patterns of generic escitalopram initiation and substitution among Medicare beneficiaries. METHODS: This retrospective new user cohort used a 5% random sample of 2013-2015 Medicare administrative claims data. Fee-for-service Medicare beneficiaries continuously enrolled in Parts A, B, and D during a 6-month washout period prior to their initial generic or brand oral escitalopram prescriptions were included (n = 12,351). The primary outcomes were generic escitalopram treatment initiation, and among brand escitalopram initiators, generic substitution within 12 months. Patient demographics, health service utilization, and prescription level factors were measured and assessed. RESULTS: Among all escitalopram initiators, about 88.2% Medicare beneficiaries initiated generic escitalopram. Beneficiaries who were younger age, male, residing in non-Northeast regions or urban area, in the Part D plan deductible benefit phase, and filling prescriptions at community/retail pharmacies were more likely to initiate generic treatment. Among brand escitalopram initiators (n = 1,464), about 20.7% switched to generic escitalopram, 31.2% switched to another alternative antidepressant, 25.1% discontinued treatment, and 8.7% were lost to follow up or passed away within 12 months after brand initiation. Factors associated with generic escitalopram substitution included region (Midwest vs. Northeast, adjusted hazard ratio (HR) = 1.46, 95% CI = 1.04-2.05), pre-index hospitalization (HR = 1.31; 95% CI = 1.16-1.48) and lower escitalopram average daily dosage (HR = 0.97; 95% CI = 0.95-0.99). CONCLUSIONS: In 2013-2015, almost 90% Medicare beneficiaries initiated generic escitalopram treatment. Among brand escitalopram initiators, about 1 in 5 patients switched to generic escitalopram within 1 year, as compared to 1 in 4 or 1 in 3 who discontinued current or switched to alternative treatment, respectively. Medicare beneficiary's geographic region was independently associated with generic escitalopram initiation and substitution. Findings from this study not only provide up-to-date evidence in generic escitalopram use patterns among Medicare population, but also can guide educational and practice interventions to further increase generic escitalopram use.

Results of a retrospective claims database analysis of differences in antidepressant treatment persistence associated with escitalopram and other selective serotonin reuptake inhibitors in the United States.

BACKGROUND: Although previous studies have found no differences in response to antidepressant pharmacotherapy between selective serotonin reuptake inhibitors (SSRIs), some recent trials suggest benefits associated with more rapid onset of action. OBJECTIVE: The aim of this work was to compare the likelihood that patients initiating treatment with branded escitalopram, rather than with any of 3 SSRIs (ie, citalopram, fluoxetine, and paroxetine) that are available in generic or branded formulations, would continue therapy with the initial medication after 2 and 6 months. METHODS: We used propensity score-weighted logistic regression to assess the effect of antidepressant choice on the likelihood of continuing treatment, based on data from a large administrative claims database with information about US patients. We modeled the propensity to initiate treatment with escitalopram based on demographic, diagnostic, insurance, and service-use characteristics in the 6 months before treatment initiation and used the results to calculate weights for analysis of treatment continuation. The primary outcome measures were receipt of 2 prescriptions of the index drug in the first 2 months and, among those continuing at 2 months, 4 prescriptions in the first 6 months. Antidepressant choice, cost, and service-use characteristics during the treatment period were included as covariates. Patients who initiated therapy between July 2002 and April 2005 were eligible for inclusion. RESULTS: Based on data for 43,921 patients, at 2 months, escitalopram initiators were more likely to have continued initial medication than those receiving the other SSRIs (66.1% vs 61.9%, respectively; P < 0.01) and less likely to have switched or augmented treatment (4.8% vs 7.6%; P < 0.01). At 6 months, escitalopramtreated patients were also more likely to have continued initial medication (47.1% vs 41.0%; P < 0.01) and less likely to have switched or augmented treatment (9.4% vs 14.4%; P < 0.01). CONCLUSION: Patients initiating treatment with escitalopram were more likely to continue and less likely to switch or augment treatment at 2 and 6 months of therapy compared with those who initiated with alternative SSRIs.

Treatment persistence, healthcare utilisation and costs in adult patients with major depressive disorder: a comparison between escitalopram and other SSRI/SNRIs.

OBJECTIVE: Compare treatment persistence, healthcare utilisation and costs for patients treated with escitalopram versus other SSRI/SNRIs in a real-world setting. METHODS: Patients with a diagnosis for major depressive disorder (MDD) and at least one prescription for an SSRI or SNRI were identified from the Ingenix Impact Database (2002-2005). The baseline and study observation periods were defined as the 6 months before and after the index date (first date for an SSRI /SNRI pharmacy claim). Comparisons were made between patients initiated on escitalopram versus other SSRI/SNRIs using descriptive statistics and multivariate regressions. RESULTS: Escitalopram patients (n=10,465) had better treatment persistence compared to patients initiated on other SSRI/SNRIs (n=28,310): the hazard ratio of all discontinuation was 0.96 (95% confidence interval [CI]=0.94-0.99) for the escitalopram therapy (p=0.003), and the hazard ratio of switching to another second-generation antidepressant was 0.91 (95% CI=0.87-0.94) for the escitalopram therapy (p<0.001). Escitalopram patients also had fewer inpatient service and emergency room visits. Adjusted average total all-cause healthcare costs and inpatient services costs were $839 and $405 lower in the escitalopram group (both p<0.05). CONCLUSIONS: Escitalopram may be associated with lower healthcare utilisation and costs among adult MDD patients compared to other SSRI/SNRIs.

Ongoing initiatives within the Scottish National Health Service to affect the prescribing of selective serotonin reuptake inhibitors and their influence.

Aim: Increasing use of selective serotonin-reuptake inhibitors (SSRIs) in Scotland, coupled with safety concerns with some SSRIs, and the increasing availability of generic SSRIs, have resulted in multiple initiatives to improve the quality and efficiency of their prescribing in Scotland. Our aim is to assess their influence to provide future direction. Materials & methods: The prescription costs analysis database was used to document utilization and expenditure on SSRIs between 2001 and 2017 alongside documenting the initiatives. Results: Multiple interventions over the years increased international nonproprietary name prescribing up to 99.9% lowering overall costs. This, coupled with initiatives to limit escitalopram prescribing due to concerns with its value, resulted in a 73.7% reduction in SSRI expenditure between 2001 and 2017 despite a 2.34-fold increase in utilization. Safety warnings resulted in a significant reduction in the prescribing of paroxetine, citalopram and escitalopram alongside a significant increase in sertraline Conclusion: Multiple initiatives have increased the quality and efficiency of SSRI prescribing in Scotland providing direction to others.

Escitalopram and duloxetine in major depressive disorder: a pharmacoeconomic comparison using UK cost data.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are approved for the treatment of major depressive disorder (MDD). The allosteric SSRI escitalopram has been shown to be at least as clinically effective as the SNRIs venlafaxine and duloxetine in MDD, with a better tolerability profile. In addition, escitalopram has been shown to be cost saving compared with venlafaxine. OBJECTIVE: To evaluate the cost effectiveness of escitalopram versus duloxetine in the treatment of MDD, and to identify key cost drivers. METHODS: The pharmacoeconomic evaluation was conducted alongside a 24-week, double-blind, multinational randomized study (escitalopram 20 mg/day and duloxetine 60 mg/day) in outpatients with MDD, aged 18-65 years, with Montgomery-Asberg Depression Rating Scale (MADRS) score >or=26 and Clinical Global Impression Severity (CGI-S) score >or=4, and baseline duration of the current depressive episode of 12 weeks to 1 year.The analysis was conducted on the full analysis set (FAS), which included all patients with >or=1 valid post-baseline health economic assessment. Effectiveness outcomes of the cost-effectiveness analyses (CEA) included the change in Sheehan Disability Scale (SDS) score (primary CEA), treatment response (MADRS score decrease >or=50%) and remission (MADRS score

Analysis of health-related quality of life and costs based on a randomised clinical trial of escitalopram for relapse prevention in patients with generalised social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) is associated with substantial reduction in health-related quality of life (HRQoL). Escitalopram has proven efficacy in the short-term treatment of SAD and prevention of relapse. OBJECTIVES: To determine whether the clinical effects of treatment translated into HRQoL benefits and to investigate costs of SAD treatment. METHODS: Data on HRQoL and resource utilisation were collected in a previously published clinical trial of escitalopram in relapse prevention. Among 517 patients, 371 responded to 12 weeks of open-label treatment with escitalopram and were randomised to escitalopram or placebo for 24 weeks. HRQoL was assessed using the short form (SF)-36 instrument and SF-6D utilities (preference-based index scores for overall HRQoL) were calculated. Costs were calculated for responders over the acute phase and for non-relapsed patients over the continuation phase, applying UK unit costs. RESULTS: Health-related quality of life was significantly improved after the acute phase when compared with baseline. The SF-6D utility increased by 0.047 in responders (p < 0.0001) and 0.021 in non-responders (p = 0.0005). Healthcare costs were non-significantly lower in acute phase than during prestudy phase (p = 0.0587 from NHS perspective), as were productivity costs (p = 0.1440). HRQoL at last visit was lower in relapsed than non-relapsed patients. The difference in utility was -0.026 (p = 0.0007). Healthcare and productivity costs were non-significantly lower in the escitalopram group than in the placebo group. CONCLUSIONS: Both effective acute treatment of SAD and prevention of relapse with escitalopram are associated with significant HRQoL benefits. Despite some limitations, the cost analysis suggests that savings in physician-visits and inpatient care may offset drug acquisition costs.

Improvements in Quality-Adjusted Life Years and Cost-Utility After Pharmacotherapy for Premenstrual Dysphoric Disorder: A Retrospective Study.

BACKGROUND AND OBJECTIVE: To investigate the cost-effectiveness of pharmacotherapy for premenstrual dysphoric disorder (PMDD), a relatively new classification of depressive disorder that is characterized by recurrent depression during the premenstrual phase of the menstrual cycle. METHODS: We performed a retrospective analysis of data from 49 previously untreated PMDD patients who visited our psychiatric department between October 2013 and February 2016 and received pharmacotherapy for 3 or 6 subsequent menstrual cycles. Quality-adjusted life years (QALYs) were estimated across individual menstrual cycles using mean EuroQoL-5D values. Direct costs per patient were estimated in order to conduct a preliminary cost-effectiveness analysis. RESULTS: Pharmacotherapy produced a 0.190-point increase in mean EuroQoL-5D score per menstrual cycle after 6 menstrual cycles and an improvement of approximately 0.2 QALYs. Based on direct costs of 156,000 yen per patient, the cost-effectiveness of pharmacotherapy was calculated to be 823,000 yen per QALY. A cost-effectiveness acceptability curve analysis indicated that escitalopram tended to be superior to sertraline when willingness to pay per QALY was over 4,000,000 yen, whereas sertraline was superior when willingness to pay was below 2,000,000 yen. CONCLUSIONS: Pharmacotherapy is cost effective for the treatment of PMDD. Moreover, escitalopram is a more cost-effective option than sertraline when willingness to pay is sufficiently high.

Use of Bayesian net benefit regression model to examine the impact of generic drug entry on the cost effectiveness of selective serotonin reuptake inhibitors in elderly depressed patients.

INTRODUCTION: Since their invention in the late 1980s and early 1990s, selective serotonin reuptake inhibitors (SSRIs) have become the primary form of pharmaceutical treatment for depression. As the patents of several top-selling SSRIs have expired or are soon to be expired, the SSRI market is expected to witness an increasing share of generic SSRIs. We explored the impact of generic drug entry on the cost effectiveness of SSRIs. METHOD: Using Medicare MarketScan claims data, we compared the cost effectiveness of sertraline, citalopram, escitalopram and fluoxetine with paroxetine in elderly depressed patients, before and after the entry of generic paroxetine. We followed users of SSRIs for 6 months, starting from the date of their first prescription of an SSRI. For each patient, we measured costs (C(i)) as total medical costs and quantified effectiveness (E(i)) as the avoidance of treatment failure, which was defined as having a break exceeding 45 days in the use of antidepressants. We then calculated individual net benefit as lambda x E(i)- C(i) and employed both net benefit and Bayesian net benefit regression models to examine the impact of generic paroxetine on the cost effectiveness of the other four SSRIs compared with paroxetine, while controlling for patients' sociodemographic characteristics, co-morbidities and patterns of medication switch. RESULTS: Deterministic analysis showed that paroxetine was dominated by most SSRIs prior to the availability of generic paroxetine, and that, after the entry of generic paroxetine, citalopram and escitalopram were dominated by paroxetine. Net benefit regression analysis found that, at a number of lambda values ($US1000, $US5000 and $US10,000), sertraline and escitalopram were more cost effective than paroxetine in the pre-generic-entry period but not in the post-entry period, although the difference in net benefit between the two SSRIs and paroxetine was not statistically significant in both periods. The Bayesian net benefit regression analysis reached similar conclusions. At lambda = $US5000, the probability that sertraline, citalopram, escitalopram or fluoxetine was more cost effective than paroxetine was 96.7%, 77.6%, 96.3% and 97.0%, respectively, in the pre-entry period in the pooled analysis. These probabilities reduced to 36.7%, 62.7%, 33.0% and 60.1%, respectively, in the post-entry period. The probabilities became 94.1%, 71.9%, 89.1% and 92.1% in analysis using the pre-entry data as a prior to update the post-entry data rather than using the pooled data. CONCLUSION: Using generic drug entry as an example, our study demonstrated the importance of including the economic life cycle of pharmaceuticals in cost-effectiveness analyses. Additionally, the proposed Bayesian framework not only preserves the advantages of the net benefit regression framework, but more importantly, it introduces the possibility of conducting probabilistic cost-effectiveness analyses with claims data.

Cost-effectiveness of escitalopram vs. citalopram in major depressive disorder.

Clinical trials have shown better efficacy of escitalopram over citalopram, and review-based economic models the cost-effectiveness of escitalopram vs. citalopram (brand and generic). No head-to-head clinical trial has, however, evaluated the cost-effectiveness of both drugs so far. The aim of this study was to assess the relative cost-effectiveness of escitalopram compared with citalopram in patients with major depressive disorder. An economic evaluation was conducted alongside a double-blind randomized clinical trial conducted by general practitioners and psychiatrists comparing fixed doses of escitalopram (20 mg/day) or citalopram (40 mg/day) over 8 weeks in ambulatory care patients with major depressive disorder (baseline Montgomery-Asberg Depression Rating Scale score > or =30). Resources use was recorded using a standardized form recording use of healthcare services and days of sick leave for the 2-month prestudy period and for the 8-week study period. Statistically significant improvements were observed in patients treated with escitalopram. Mean per-patient costs for the escitalopram group, compared with the citalopram group, were 41% lower (96 euro vs. 163 euro; P<0.05) from a healthcare perspective. Differences were mostly related to lower hospitalization costs for escitalopram compared with citalopram recipients, assuming a parity price between escitalopram and citalopram. Bootstrapped distributions of the cost-effectiveness ratios also showed better effectiveness and lower costs for escitalopram compared with citalopram. Escitalopram is significantly more effective than citalopram, and is associated with lower healthcare costs. This prospective economic analysis demonstrated that escitalopram is a cost-effective first-line treatment option for major depressive disorder.

Cost-effectiveness analysis of escitalopram compared with paroxetine in treatment of generalized anxiety disorder in the United Kingdom.

BACKGROUND: Generalized anxiety disorder (GAD) is associated with substantial economic burden. OBJECTIVE: To assess, from a societal perspective, the cost-effectiveness of escitalopram and paroxetine in the treatment of GAD in the UK. METHOD: A decision analytic model with a 9 month time horizon was adapted to the UK setting. Model inputs included drug- and nondrug-specific probabilities from head-to-head trial data, published literature, and expert opinion. Main outcome measures were success (response after 12 wk of treatment and no relapse during the following 24 wk) and costs. Resource use was based on National Institute for Health and Clinical Excellence guidance for GAD patient management, and estimated unit costs came from standard national sources. Human capital approach was used to estimate costs of absence from work. The analysis was performed from the societal perspective. RESULTS: Escitalopram-treated patients were associated with 14.4% higher first-line treatment success and significantly lower discontinuation rates due to adverse events than were those treated with paroxetine. Treatment with escitalopram yielded lower expected costs with greater effectiveness compared with paroxetine. These clinical advantages led to less sick leave and resource use as a result of lower switch rates and use of secondary care. Total expected 9 month costs were 1408 pounds sterling (2560 US dollars) lower for escitalopram-treated patients than for paroxetine-treated patients. Sensitivity analyses on key parameters demonstrated robustness of the model. CONCLUSIONS: Escitalopram appears to be cost-effective compared with paroxetine in the treatment of GAD in the UK.