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.

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.

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings.

INTRODUCTION: Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths. Areas covered: Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotsericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent. Expert commentary: Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging.

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 prolonged exposure therapy versus pharmacotherapy and treatment choice in posttraumatic stress disorder (the Optimizing PTSD Treatment Trial): a doubly randomized preference trial.

OBJECTIVE: Cost-effectiveness of treatment for posttraumatic stress disorder (PTSD) may depend on type of treatment (eg, pharmacotherapy vs psychotherapy) and patient choice of treatment. We examined the cost-effectiveness of treatment with prolonged exposure therapy versus pharmacotherapy with sertraline, overall treatment preference, preference for choosing prolonged exposure therapy, and preference for choosing pharmacotherapy with sertraline from the US societal perspective. METHOD: Two hundred patients aged 18 to 65 years with PTSD diagnosis based on DSM-IV criteria enrolled in a doubly randomized preference trial. Patients were randomized to receive their treatment of choice (n = 97) or to be randomly assigned treatment (n = 103). In the choice arm, patients chose either prolonged exposure therapy (n = 61) or pharmacotherapy with sertraline (n = 36). In the no-choice arm, patients were randomized to either prolonged exposure therapy (n = 48) or pharmacotherapy with sertraline (n = 55). The total costs, including direct medical costs, direct nonmedical costs, and indirect costs, were estimated in 2012 US dollars; and total quality-adjusted life-year (QALY) was assessed using the EuroQoL Questionnaire-5 dimensions (EQ-5D) instrument in a 12-month period. This study was conducted from July 2004 to January 2009. RESULTS: Relative to pharmacotherapy with sertraline, prolonged exposure therapy was less costly (-$262; 95% CI, -$5,068 to $4,946) and produced more QALYs (0.056; 95% CI, 0.014 to 0.100) when treatment was assigned, with 93.2% probability of being cost-effective at $100,000/QALY. Independently, giving a choice of treatment also yielded lower cost (-$1,826; 95% CI, -$4,634 to $749) and more QALYs (0.010; 95% CI, -0.019 to 0.044) over no choice of treatment, with 87.0% probability of cost-effectiveness at $100,000/QALY. CONCLUSIONS: Giving PTSD patients a choice of treatment appears to be cost-effective. When choice is not possible, prolonged exposure therapy may provide a cost-effective option over pharmacotherapy with sertraline. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00127673.

Economic evaluation of St. John's wort (Hypericum perforatum) for the treatment of mild to moderate depression.

BACKGROUND: The burden of rising health care expenditures has created a demand for information regarding the clinical and economic outcomes associated with Complementary and Alternative Medicines. Clinical controlled trials have found St. John's wort to be as effective as antidepressants in the treatment of mild to moderate depression. The objective of this study was to develop a model to assess the cost-effectiveness of St. John's wort based on this evidence. METHODS: A Markov model was constructed to estimate health and economic impacts of St. John's wort versus antidepressants. Outcomes were treatment costs, quality-adjusted life years (QALYs) and Net Monetary Benefits (NMB). Probabilistic analyses were conducted on key model parameters. RESULTS: The average NMB across 5000 simulations identified St. John's wort as the strategy with the highest net benefit. The total cost savings for SJW were $359.66 and $202.56 per individual for venlafaxine and sertraline respectively, with a gain of 0.08 to 0.12 QALYs over the 72 weeks of the model. LIMITATIONS: A lack of direct comparative clinical trial data comparing SJW to venlafaxine and limited data with sertraline as a comparator was a major limitation. CONCLUSIONS: In this model, St. John's wort was shown to be a cost-effective alternative to generic antidepressants. Patients are more likely to receive treatment for a duration consistent with professional guidelines for treatment of major depression due to reduced incidence of adverse effects, improving outcomes. This represents an important option in the treatment of Major Depressive Disorder.

Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial.

BACKGROUND: Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. AIMS: To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. METHOD: A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. RESULTS: There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively. CONCLUSIONS: In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.

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.

Cost-effectiveness analysis of burning mouth syndrome therapy.

OBJECTIVE: To study the cost-effectiveness of four alternative treatments for burning mouth syndrome (BMS). METHODS: A cost-effectiveness analysis was conducted from a healthcare payer perspective of four therapy strategies (amisulpride, paroxetine, sertraline and topical clonazepam), using a decision-tree model that incorporated direct healthcare costs and probabilities associated with the possible events and outcomes. Average cost-effectiveness and incremental cost-effectiveness ratios were calculated. Sensitivity analyses included the costs of brand name and generic drugs in five European countries (France, Italy, the Netherlands, Spain and UK), as well as two scenarios with different treatment length. RESULTS: Of the drugs analysed, topical clonazepam proved to be the most cost-effective therapy. Although generic proved more efficient than brand name drugs, they displayed no advantage over brand name topical clonazepam. The Netherlands was the country with the highest overall drug efficiency. Sensitivity analyses highlighted the robustness of the model, because topical clonazepam proved to be the most efficient therapy under all the different scenarios. CONCLUSIONS: Topical clonazepam, which previous analyses of clinical evidence have shown to be the drug of choice for BMS, also proved to be the most cost-effective of the drugs analysed for this condition.

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.

Cost-effectiveness analysis of treatments for premenstrual dysphoric disorder.

BACKGROUND: Premenstrual syndrome (PMS) is reported to affect between 13% and 31% of women. Between 3% and 8% of women are reported to meet criteria for the more severe form of PMS, premenstrual dysphoric disorder (PMDD). Although PMDD has received increased attention in recent years, the cost effectiveness of treatments for PMDD remains unknown. OBJECTIVE: To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE). METHODS: A decision-analytic model was used to evaluate both direct costs (medication and physician visits) and clinical outcomes (treatment success, failure and discontinuation). Medication costs were based on average wholesale prices of branded products; physician visit costs were obtained from a claims database study of PMDD patients and the Agency for Healthcare Research and Quality. Clinical outcome probabilities were derived from published clinical trials in PMDD. The incremental cost-effectiveness ratio (ICER) was calculated using the difference in costs and percentage of successfully treated patients at 6 months. Deterministic and probabilistic sensitivity analyses were used to assess the impact of uncertainty in parameter estimates. Threshold values where a change in the cost-effective strategy occurred were identified using a net benefit framework. RESULTS: Starting therapy with DRSP/EE dominated both sertraline and paroxetine, but not fluoxetine. The estimated ICER of initiating treatment with fluoxetine relative to DRSP/EE was $US4385 per treatment success (year 2007 values). Cost-effectiveness acceptability curves revealed that for ceiling ratios>or=$US3450 per treatment success, fluoxetine had the highest probability (>or=0.37) of being the most cost-effective treatment, relative to the other options. The cost-effectiveness acceptability frontier further indicated that DRSP/EE remained the option with the highest expected net monetary benefit for ceiling values

Time to relapse after short- or long-term treatment of severe premenstrual syndrome with sertraline.

CONTEXT: The duration of treatment after achieving a satisfactory response is unknown in the treatment of premenstrual syndrome. This information is needed in view of the improvement provided by medication vs the adverse effects and costs of drugs. OBJECTIVE: To compare rates of relapse and time to relapse between short- and long-term treatment with sertraline hydrochloride administered in the luteal phase of the menstrual cycle. DESIGN: Eighteen-month survival study with a randomized double-blind switch to placebo after 4 or 12 months of sertraline treatment. SETTING: Academic medical center. PARTICIPANTS: One hundred seventy-four patients with premenstrual syndrome or premenstrual dysphoric disorder. MAIN OUTCOME MEASURE: Relapse, defined as symptoms returning to the entry criterion level as assessed with daily ratings. RESULTS: The relapse rate was 41% during long-term treatment compared with 60% after short-term sertraline therapy, with a median time to relapse of 8 months vs 4 months (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P = .04). Patients with severe symptoms at baseline were more likely to experience relapse compared with patients in the lower symptom severity group (hazard ratio, 2.02; 95% confidence interval, 1.18-3.41; P = .01) and were more likely to experience relapse with short-term treatment (P = .03). Duration of treatment did not affect relapse in patients in the lower symptom severity group (P = .50). Patients who demonstrated remission were least likely to experience relapse (hazard ratio, 0.22; 95% confidence interval, 0.10-0.45; P < .001). Further analysis comparing relapse in the first 6 months of placebo treatment in each group yielded similar results. CONCLUSIONS: The relapse rate was significantly greater after short-term treatment compared with long-term treatment. The relapse rate was also high during extended drug treatment. Subjects with severe symptoms at baseline were most likely to experience relapse, and relapse occurred more swiftly regardless of treatment duration. These findings suggest that the severity of symptoms at baseline and symptom remission with treatment should be considered in determining the duration of treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00318773.

The cost-effectiveness of sertraline in the treatment of depression.

Depressive disorders are common conditions that place a large burden of illness on patients, employers, payers, and society. Although efficacious interventions exist to treat various forms of the condition, substantial gaps in care remain. The selective serotonin re-uptake inhibitors (SSRIs) represent the most commonly utilized drug class for the treatment of depression; sertraline is the most prescribed single agent and received generic drug approval in 2006. The results of pharmacoeconomic analyses comparing the costs and outcomes of sertraline with other antidepressants are mixed; in particular, investigations emphasize branded medications relative to costs. Continued research is needed to support decision making given recent changes in the antidepressant marketplace, particularly the introduction of generic sertraline and newer agents, and the complexity that surrounds the management of depressive disorders.

Sertraline treatment for depression associated with acute coronary syndromes: a cost analysis from the viewpoint of the Italian Healthcare System.

BACKGROUND AND AIMS: Depressive disorders (DD) are independent risk factors for rehospitalization after acute coronary syndromes (ACS) and, hence, for increased healthcare costs. A placebo-controlled safety trial of 24 weeks of treatment with sertraline after ACS (Sertraline Anti-Depressant Heart Attack Randomized Trial, SADHART) suggested that active treatment was associated with reduced rehospitalization due to coronary and non-coronary events. With the SADHART database, a cost analysis was carried out to determine the economic consequences of treating DD after ACS in the perspective of the Italian Healthcare System. METHODS: Clinical information on medical events and rehospitalizations recorded over the study period was drawn from the original SADHART database, which did not contain information necessary for estimating indirect costs. Analysis was therefore limited to direct medical costs due to rehospitalizations, emergency room visits and hospital procedures, and the average Italian Diagnosis-Related Group (DRG) tariffs were applied. RESULTS: With the exclusion of the cost of sertraline treatment, the average direct cost per patient over the study period was 3,418+/-8,290 euro in the active treatment group and 4,409+/-9,439 euro in the placebo group (p=0.3). After including the cost of 24 weeks of sertraline treatment, the average cost in sertraline-treated patients was only modestly increased, to 3,524+/-8,290 euro. CONCLUSIONS: Treatment of major DD in patients with recent ACS can improve patient care without additional costs, and possibly with some savings, to the healthcare system.

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-utility comparison of escitalopram and sertraline in the treatment of major depressive disorder.

OBJECTIVE: To construct a cost-utility model comparing escitalopram with sertraline in the treatment of major depressive disorders. METHODS: A decision analytic model was created to compare the cost-utility of these two antidepressants from the perspective of a managed-care organization. The model was designed to compare 10-20 mg/day of escitalopram to 50-200 mg/day of sertraline. Benefits (utility) scores were calculated based on clinical and utility data obtained from the literature. Direct medical costs included costs of the antidepressants, titration, treatment failures, and adverse events. Costs and benefits were modeled for a 6-month period and the model was subjected to thorough sensitivity analyses. RESULTS: The estimated 6-month total cost was 919 dollars for escitalopram and 1351 dollars for sertraline. The estimated QALYs were 0.40296 for escitalopram and 0.39268 for sertraline. These differences were mostly due to differences in drug acquisition costs and adverse events. The robustness of the cost-utility model results were tested in a Monte Carlo simulation of 10 000 patients and it indicated an 88.5% probability that escitalopram was the dominant therapy, suggesting both lower costs and greater QALYs. CONCLUSION: This cost-utility model that incorporated the costs of titration and impact of side-effects comparing escitalopram 10-20 mg per day and sertraline 50-200 mg per day shows that escitalopram appeared to be less costly and produced efficacy (utility) at least as good as and maybe slightly better than that of sertraline.

Cost-utility of selective serotonin reuptake inhibitors for depression in primary care in Catalonia.

OBJECTIVE: To determine the cost-utility of selective serotonin reuptake inhibitors (SSRIs) for treating depressive disorders prescribed in primary care (PC). METHOD: A total of 301 participants beginning antidepressant treatment with an SSRI were enrolled in a prospective 6-month follow-up naturalistic study. Incremental cost-utility ratios (ICUR) were obtained for several comparisons among different SSRIs. To address uncertainty in the ICUR's sampling distribution, non-parametric bootstrapping was carried out. RESULTS: Taking into account adjusted total costs and incremental quality of life gained, fluoxetine dominated paroxetine and citalopram with 63.4% and 79.3% of the bootstrap replications in the dominance quadrant, respectively. Additionally, fluoxetine was cost-effective over sertraline with 83.4% of the bootstrap replications below the threshold of 33,936 US$/quality-adjusted life year (30,000 euro/QALY). CONCLUSION: Fluoxetine seems to be a better cost-utility SSRI option for treating depressive disorders in PC.

Initial results of the use of prescription order change forms to achieve dose form optimization (consolidation and tablet splitting) of SSRI antidepressants in a state Medicaid program.

BACKGROUND: One method to reduce drug costs is to promote dose form optimization strategies that take advantage of the flat pricing of some drugs, i.e., the same or nearly the same price for a 100 mg tablet and a 50 mg tablet of the same drug. Dose form optimization includes tablet splitting; taking half of a higher-strength tablet; and dose form consolidation, using 1 higher-strength tablet instead of 2 lower-strength tablets. Dose form optimization can reduce the direct cost of therapy by up to 50% while continuing the same daily dose of the same drug molecule. OBJECTIVE: To determine if voluntary prescription change forms for antidepressant drugs could induce dosing changes and reduce the cost of antidepressant therapy in a Medicaid population. METHODS: Specific regimens of 4 selective serotonin reuptake inhibitors (SSRIs)- citalopram, escitalopram, paroxetine, and sertraline- were identified for conversion to half tablets or dose optimization. Change forms, which served as valid prescriptions, were faxed to Oregon prescribers in October 2004. The results from both the returned forms and subsequent drug claims data were evaluated using a segmented linear regression. Citalopram claims were excluded from the cost analysis because the drug became available in generic form in October 2004. RESULTS: A total of 1,582 change forms were sent to 556 unique prescribers; 9.2% of the change forms were for dose consolidation and 90.8% were for tablet splitting. Of the 1,118 change forms (70.7%) that were returned, 956 (60.4% of those sent and 85.5% of those returned) authorized a prescription change to a lower-cost dose regimen. The average drug cost per day declined by 14.2%, from Dollars 2.26 to Dollars 1.94 in the intervention group, versus a 1.6% increase, from Dollars 2.52 to Dollars 2.56, in the group without dose consolidation or tablet splitting of the 3 SSRIs (sertraline, escitalopram, and immediate-release paroxetine). Total drug cost for the 3 SSRIs declined by 35.6%, from Dollars 333,567 to Dollars 214,794, as a result of a 24.8% decline in the total days of SSRI drug therapy and the 14.2% decline in average SSRI drug cost per day. The estimated monthly cost avoidance from this intervention, based on pharmacy claims data, was approximately Dollars 35,285, about 2% of the entire spending on SSRI drugs each month, or about Dollars 0.09 per member per month. Program administration costs, excluding costs incurred by prescribers and pharmacy providers, were about 2% of SSRI drug cost savings. CONCLUSIONS: Voluntary prescription change forms appear to be an effective and well-accepted tool for obtaining dose form optimization through dose form consolidation and tablet splitting, resulting in reduction in the direct costs of SSRI antidepressant drug therapy with minimal additional program administration costs.