Benefit of slow titration of paroxetine to treat depression in the elderly.

OBJECTIVE: Paroxetine is commonly used to treat depression in the elderly; however, titration issues have been raised. Rapid titration may lead to increased anxiety and early dropout. The aim of this cost-utility analysis was to compare the potential benefit of standard (10 mg the first day) versus slow titration (2.5 mg gradually increased). METHODS: Clinical analysis was based on a naturalistic trial integrated with a decision-analytic model representing second treatments for those who initially did not respond and for dropout cases. Treatment setting was a public outpatient center for mental disorders in Italy. Service use data were estimated from best practice guidelines, whereas costs (Euros; 2012) were retrieved from Italian official sources. RESULTS: Slow titration approach produced 0.031 more quality-adjusted life years (remission rate: 57% vs 44% in standard titration group) at an incremental cost of €5.53 (generic paroxetine) and €54.54 (brand paroxetine syrup). Incremental cost-effectiveness ratio (ICER) values were €159 and €1768, respectively, in favor of slow titration approach. Cost-effectiveness threshold, defined as ICER < 1 GDP per capita according to World Health Organization criteria, is about €25 000 in Italy. CONCLUSIONS: Our results are consistent with a superiority of slow titration of paroxetine in older depressed patients. However, these findings, in part based on simulated data, need to be replicated in clinical trials.

Incremental cost-effectiveness of pharmacotherapy and two brief cognitive-behavioral therapies compared with usual care for panic disorder and noncardiac chest pain.

The aim of this study was to assess the incremental cost-effectiveness ratios (ICERs) of two brief cognitive-behavioral therapy (CBT)-based interventions and a pharmacological treatment, compared with usual care, initiated in the emergency department (ED) for individuals with panic disorder (PD) with a chief complaint of noncardiac chest pain. A total of 69 patients were followed up to 6 months. The primary outcome variables were direct and indirect costs of treatment and PD severity. Panic management (PM) had an ICER of $124.05, per the Anxiety Disorders Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, severity score change (95% confidence interval [CI], $54.63-$314.57), compared with pharmacotherapy (paroxetine), with an ICER of $213.90 (95% CI, $133.51-$394.94), and brief CBT, with an ICER of $309.31 (95% CI, $151.27-$548.28). The pharmacological and CBT interventions were associated with a greater clinical improvement compared with usual care at posttest. PM presented a superior ICER, suggesting that it may be a promising treatment option to implement in EDs.

Comparison of the effectiveness of trauma-focused cognitive behavioral therapy and paroxetine treatment in PTSD patients: design of a randomized controlled trial.

BACKGROUND: The two most common interventions for Posttraumatic Stress Disorder (PTSD) are pharmacological treatment with SSRIs such as paroxetine and psychological treatment such as Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). International guidelines recommend trauma-focused psychological interventions for all PTSD patients as first-line treatment (NICE). However, no clear-cut evidence is available to support this recommendation. METHODS/DESIGN: In order to compare pharmacological treatment (paroxetine) and psychological treatment (TF-CBT) in (cost-) effectiveness on the short and the long term, we will randomize 90 patients with chronic PTSD to either paroxetine (24 weeks) or TF-CBT (10-12 weeks). We will assess symptom severity and costs before and after the intervention with the Clinician Administered PTSD Scale (CAPS), the Clinical Global Impression Scale (CGI) and the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness (TiC-P). DISCUSSION: This study is unique for its direct comparison of the most commonly used psychological intervention (TF-CBT) and pharmacological intervention (paroxetine) on (cost-) effectiveness on the short and the long term. The anticipated results will provide relevant evidence concerning long-term effects and relapse rates and will be beneficial in reducing societal costs. It may also provide information on who may benefit most from which type of intervention. Some methodological issues will be discussed. TRIAL REGISTRATION: Dutch Trial registration: NTR2235.

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.

The relationship between somatisation and outcome in patients with severe irritable bowel syndrome.

OBJECTIVE: This study aimed to assess the relationship between somatisation and outcome in patients with severe irritable bowel syndrome (IBS). METHOD: Two hundred fifty-seven patients with severe IBS included in a randomised controlled trial were assessed at baseline and divided into four quartiles on the basis of their somatisation score. The patients were randomised to receive the following over 3 months: brief interpersonal psychotherapy, 20 mg daily of the SSRI antidepressant paroxetine, or treatment as usual. Outcome 1 year after treatment was assessed using the Short Form-36 physical component summary (PCS) score and total costs for posttreatment year. RESULTS: The patients in the quartile with the highest baseline somatisation score had the most severe IBS, the most concurrent psychiatric disorders, and the highest total costs for the year prior to baseline. At 1 year after the end of treatment, however, the patients with marked somatisation, who received psychotherapy or antidepressant, had improved health status compared to those who received usual care: mean (S.E.) PCS scores at 15 months were 36.6 (2.2), 35.5 (1.9), and 26.4 (2.7) for psychotherapy, antidepressant, and treatment-as-usual groups, respectively (adjusted P=.014). Corresponding data for total costs over the year following the trial, adjusted for baseline costs, were pound 1092 (487), pound 1394 (443), and pound 2949 (593) (adjusted P=.050). CONCLUSIONS: Patients with severe IBS who have marked somatisation improve with treatment like other IBS patients and show a greater reduction of costs. Antidepressants and psychotherapy are cost-effective treatments in severe IBS accompanied by marked somatisation.

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 evidence-based pharmacotherapy or cognitive behavior therapy compared with community referral for major depression in predominantly low-income minority women.

BACKGROUND: Few clinical trials have evaluated interventions for major depressive disorder in samples of low-income minority women, and little is known about the cost-effectiveness of depression interventions for this population. OBJECTIVE: To evaluate the cost-effectiveness of pharmacotherapy or cognitive behavior therapy (CBT) compared with community referral for major depression in low-income minority women. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted in 267 women with current major depression. INTERVENTIONS: Participants were randomly assigned to pharmacotherapy (paroxetine hydrochloride or bupropion hydrochloride) (n = 88), CBT (n = 90), or community referral (n = 89). MAIN OUTCOME MEASURES: The main outcomes were intervention and health care costs, depression-free days, and quality-adjusted life years based on Hamilton Depression Rating Scale scores and Medical Outcomes Study 36-Item Short-Form Health Survey summary scores for 12 months. Cost-effectiveness ratios were estimated to compare incremental patient outcomes with incremental costs for pharmacotherapy relative to community referral and for CBT relative to community referral. RESULTS: Compared with the community referral group, the pharmacotherapy group had significantly lower adjusted mean Hamilton Depression Rating Scale scores from the 3rd month through the 10th month (P = .04 to P<.001) of the study, and the CBT group had significantly lower adjusted mean scores from the 5th month through the 10th month (P = .03 to P = .049). There were significantly more depression-free days in the pharmacotherapy group (mean, 39.7; 95% confidence interval, 12.9-66.5) and the CBT group (mean, 25.80; 95% confidence interval, 0.04-51.50) than in the community referral group. The cost per additional depression-free day was USD 24.65 for pharmacotherapy and USD 27.04 for CBT compared with community referral. CONCLUSIONS: Effective treatment for depression in low-income minority women reduces depressive symptoms but increases costs compared with community referral. The pharmacotherapy and CBT interventions were cost-effective relative to community referral for the health care system.

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.

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.

Cost-effectiveness and cost offset of a collaborative care intervention for primary care patients with panic disorder.

BACKGROUND: A collaborative care (CC) intervention for patients with panic disorder that provided increased patient education and integrated a psychiatrist into primary care was associated with improved symptomatic and functional outcomes. This report evaluates the incremental cost-effectiveness and potential cost offset of a CC treatment program for primary care patients with panic disorder from the perspective of the payer. METHODS: We randomly assigned 115 primary care patients with panic disorder to a CC intervention that included systematic patient education and approximately 2 visits with an on-site consulting psychiatrist, compared with usual primary care. Telephone assessments of clinical outcomes were performed at 3, 6, 9, and 12 months. Use of health care services and costs were assessed using administrative data from the primary care clinics and self-report data. RESULTS: Patients receiving CC experienced a mean of 74.2 more anxiety-free days during the 12-month intervention (95% confidence interval [CI], 15.8-122.0). The incremental mental health cost of the CC intervention was $205 (95% CI, -$135 to $501), with the additional mental health costs of the intervention explained by expenditures for antidepressant medication and outpatient mental health visits. Total outpatient cost was $325 (95% CI, -$1460 to $448) less for the CC than for the usual care group. The incremental cost-effectiveness ratio for total ambulatory cost was -$4 (95% CI, -$23 to $14) per anxiety-free day. Results of a bootstrap analysis suggested a 0.70 probability that the CC intervention was dominant (eg, lower costs and greater effectiveness). CONCLUSION: A CC intervention for patients with panic disorder was associated with significantly more anxiety-free days, no significant differences in total outpatient costs, and a distribution of the cost-effectiveness ratio based on total outpatient costs that suggests a 70% probability that the intervention was dominant, compared with usual care.

Differences in total medical costs across the SSRIs for the treatment of depression and anxiety.

There is growing evidence that adherence to the recommended duration of antidepressant therapy results in reduced medical costs compared with nonadherence, and that the likelihood of adhering to therapy is not equivalent across the selective serotonin reuptake inhibitors (SSRIs). As such, the purpose of this study was to assess differences in 6-month medical costs between paroxetine controlled-release (CR) and immediate-release (IR) SSRI agents in a retrospective analysis of patients initiating SSRI therapy identified from the Integrated Healthcare Information Services National Managed Care Benchmark Database during a 2.5-year time frame. Inferential analyses were performed to evaluate differences in 6-month medical costs, controlling for differences in age, sex, utilization of psychiatric specialty care services, titration, pre-period costs, and comorbidity measures. Of the 146 075 patients included in this study, approximately 7% received paroxetine CR. Approximately 29.5% of patients had an anxiety disorder diagnosis; 26.0% had a depression-only diagnosis; and 13.2% had comorbid anxiety and depression. The 6-month medical costs were 244 US dollars lower for patients initiating with paroxetine CR compared with the average medical costs for patients receiving IR SSRIs. Paroxetine CR also had the lowest medical costs compared with each individual SSRI evaluated. After log transformation of costs and adjustment for baseline covariates, the aggregated IR SSRIs were associated with 8.7% higher 6-month medical costs than paroxetine CR (P <.001) and even greater costs after stratifying by diagnosis: 12.5% higher costs in patients with anxiety, 14.3% higher costs in patients with depression, and 15.9% higher costs in patients with comorbid anxiety and depression (P <.001 for all). Each individual IR SSRI was also associated with significantly higher medical costs than paroxetine CR, irrespective of diagnosis. As demonstrated, medical costs over a 6-month time frame were significantly greater for IR SSRIs versus paroxetine CR, even after adjusting for background characteristics and stratifying by diagnosis. Future studies should measure rates of adherence in relation to medical outcomes over an expanded time frame.

Duration of therapy and health care costs of fluoxetine, paroxetine, and sertraline in 6 health plans.

BACKGROUND: Previous studies comparing fluoxetine, paroxetine, and sertraline, the 3 most common selective serotonin reuptake inhibitors (SSRIs), in naturalistic settings have produced conflicting results. With this study, we provide new evidence as to the similarities and differences among these SSRI therapies with respect to the duration of use and health care costs. METHOD: Data from 6 health maintenance organizations were used to identify patients with new-onset major depression. number of days with filled prescriptions, and total health care and depression-related costs. The sample consisted of 1771 patients given initial prescriptions for sertraline (N = 386), fluoxetine (N = 840), or paroxetine (N = 545) in the period from July 1, 1994, to March 31, 1997. Analyses included Cox proportional hazards models (for duration of initial therapy) and ordinary least squares regression (for cost). RESULTS: Patients who initiated therapy with fluoxetine were more likely to have a later interruption of therapy than patients who initiated therapy with sertraline (p = .03) and paroxetine (p = .001). Total 1-year costs did not differ statistically between the treatment groups, but 1-year depression-related costs were significantly lower for patients who initiated therapy with sertraline or paroxetine than for those who initiated therapy with fluoxetine ($332 less for sertraline, 95% confidence interval [CI] = $125 to $562; $339 less for paroxetine, 95% CI = $144 to $416). LIMITATIONS: A limitation of this observational study, as well as of observational studies in general, is that unobserved characteristics of the patients may lead to biased estimates of the impact of treatment on adherence or cost, even with controls for observed characteristics. CONCLUSION: We found no significant differences in total health care costs among the 3 SSRIs, but noted significant differences in depression-related costs (the costs of fluoxetine are greater than those of sertraline and paroxetine). Importantly, there was no relationship between treatment interruption and increased health care or depression-related costs, in contrast to the findings of some, but not all, prior studies.

The effect of selective serotonin reuptake inhibitor treatment of panic disorder on emergency room and laboratory resource utilization.

BACKGROUND: While it has been well documented that patients with untreated panic disorder frequently utilize emergency room (ER) and laboratory services, no published data evaluate whether selective serotonin reuptake inhibitor (SSRI) treatment of patients with panic disorder is associated with decreased use of these services in the managed care organization setting. METHOD: A medical and pharmacy claims database representing individuals from several managed care organizations was used to analyze ER and laboratory resource utilization and cost for 120 patients with panic disorder (ICD-9-CM criteria) who received SSRI treatment. RESULTS: SSRI treatment was associated with a reduction in the mean number of ER and laboratory visits and costs in the 6-month period following therapy initiation compared with the 6-month period prior to therapy initiation (sertraline: visits, -79.5%; costs, -85.2%; p < .05; fluoxetine: visits, -25.0%; costs, -69.5%; p = NS; and paroxetine: visits, -8.6%; costs, -30.8%; p = NS). CONCLUSION: The results of the current study suggest that appropriate treatment of panic disorder may decrease unnecessary resource utilization for the medical symptoms associated with panic disorder.

Using forecasting models to estimate the effects of changes in the composition of claims for selective serotonin reuptake inhibitors on expenditures.

BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) as antidepressant therapy has increased considerably since the introduction of fluoxetine in 1989. By 1999, 3 of the 4 available SSRIs were among the top 10 most frequently used drugs in the United States. In addition, SSRIs were one of the major contributors to the growth in psychotropic medication expenditures during the past 5 years. OBJECTIVE: The purpose of this article was to examine the utilization patterns of the 4 most commonly used SSRIs and their contribution to rising antidepressant medication expenditures among claimants in a publicly funded drug program. Using the results of forecasting models, we explored possible ways to control these growing expenditures. METHODS: Cross-sectional antidepressant claims and expenditure data from the Ontario Drug Benefits program for 1992 to 1998 were examined. Five scenarios were modeled in which future SSRI expenditures and claims were predicted using exponential smoothing models. RESULTS: If the historical patterns of use continued, a 20% increase in the 1998 level of expenditures was expected to occur by the year 2000. Predicted expenditures are sensitive to the composition of the SSRI claims. Exclusive use of 1 of the 4 major SSRIs (fluvoxamine, fluoxetine, paroxetine, and sertraline) could decrease projected expenditures by 30% or increase them by 11%. An "equal shares" approach, in which each of the 4 SSRIs are used in equal proportions in the population, may reduce expenditures by approximately 8%. CONCLUSIONS: The current trends in the utilization data suggest that sertraline and paroxetine are being used as first-line treatments. The results of the forecasting models suggest that growing expenditures could be curbed if these 2 antidepressants were not used in that manner. Short of limiting the drugs available on benefit formularies, there may be a way to control costs through the use of a prescribing algorithm. Although our results support the use of fluoxetine for first-line SSRI treatment as a cost-control measure, we do not definitively recommend its adoption. These findings contribute to the discussion about using fixed versus flexible formularies as a potential cost-control mechanism.

A retrospective analysis of the revocation of prior authorization restrictions and the use of antidepressant medications for treating major depressive disorder.

BACKGROUND: The California Medicaid (Medi-Cal) program removed prior authorization restrictions for 2 selective serotonin reuptake inhibitors (SSRIs), fluoxetine and paroxetine, in May 1996. OBJECTIVE: This article documents how open access affected patient compliance and the likelihood of switching antidepressant therapies. METHODS: All Medi-Cal patients with a paid claim who had a diagnosis of major depressive disorder (MDD) from September 1994 through January 1999 were eligible. The impact of open access on patient compliance and drug switching was investigated using logistic regression models. Completed therapy was defined as 180 days of uninterrupted drug therapy at a minimum therapeutic dose. RESULTS: A total of 6409 patient treatment episodes were identified, of which 80% involved the use of an antidepressant. The aggregate rate of drug therapy completion dropped from 23.2% before the change in formulary policy to 20.5% in the open-access period. There was no corresponding change in the likelihood of switching therapies. For fluoxetine-treated patients, the odds ratio for completing therapy relative to tricyclic antidepressant-treated patients dropped from 3.916 to 1.706 in the open-access period. Corresponding results for paroxetine-treated patients were 1.591 and 0.726, respectively. The reduction in the likelihood of completed therapy without a corresponding increase in switching is consistent with earlier results. Open access resulted in an influx of patients who were not previously treated with an antidepressant or reported by their physician as having an MDD. Physicians may have expanded the use of the open-access SSRIs to treat less severely ill patients. However, paid claims data do not provide sufficient information to accurately measure severity of illness. CONCLUSIONS: It is unclear whether patients benefited clinically from the expansion of the Medi-Cal formulary. The significant changes in the characteristics of the patient population in response to open access (access effect) complicate attempts to measure the impact of open access on treatment patterns. Future analysis of the impact of open access on the cost of treating an episode of depression will also have to address this issue.

Comparing SSRI treatment costs for depression using retrospective claims data: the role of nonrandom selection and skewed data.

BACKGROUND AND OBJECTIVES: Since conventional randomized clinical trials often do not reflect the real world circumstances of prescribing behavior and patient outcomes, the use of retrospective administrative claims databases (RACD) has become more common in treatment cost comparisons among alternative pharmaceutical compounds. Several recent RACD studies have compared treatment costs for depressed patients prescribed SSRIs such as fluoxetine, sertraline and paroxetine. These cost comparisons have reached mixed conclusions. To begin to explain and reconcile the mixed SSRI cost comparison evidence, we undertake a variety of alternative multivariate analyses using a publicly available RACD. METHODS AND DATA: The 1995 to 1996 data encompasses a time period when all three SSRIs had become well-established agents. We report and compare results from multivariate linear regressions, logistic regressions, ordered probits and sample selectivity models, and examine robustness when adjustments are made for outlier observations and skewed distributions. RESULTS AND CONCLUSIONS: While choice of initial SSRI is nonrandom, the effect of sample selectivity on total depression-related and total health care expenditure is neutral across SSRIs. Although most cost measures are numerically greatest for fluoxetine, depression-related outpatient and hospitalization costs do not significantly differ by choice of initial SSRI. These findings are robust to alternative assumptions, specifications, and procedures. Antidepressant medication costs, however, are significantly higher when fluoxetine is the initial SSRI rather than sertraline or paroxetine, reflecting the larger proportion of fluoxetine patients prescribed a daily dosage of two or more capsules. Both total depression-related and total health care log-transformed costs are significantly lower for sertraline than fluoxetine.

Tricyclic antidepressant and selective serotonin reuptake inhibitors antidepressant selection and health care costs in the naturalistic setting: a multivariate analysis.

BACKGROUND: Providers and payers have an interest in the total health care costs following the initiation of antidepressant treatment in the real world of clinical practice. Analyses of these costs can help evaluate the economic consequences of patient management decisions associated with initial antidepressant selection. OBJECTIVE: The purpose of this study was to assess the 1-year total direct health care costs for patients initiating therapy with one of the available tricyclic antidepressants (TCAs) or one of the three most often prescribed selective serotonin reuptake inhibitors (SSRIs) - paroxetine, sertraline, or fluoxetine. METHOD: A two-stage multivariate econometric model and data from fee-for-service private insurance claims between 1990 and 1994 were used to estimate the total direct health care costs following initial antidepressant drug selection for 2693 patients with a 'new' episode of antidepressant treatment. After controlling for both observed and unobserved characteristics, the 1-year total direct health care costs were found to be (1) statistically significantly lower for patients initiating therapy on fluoxetine than for patients initiating therapy on a TCA; (2) statistically significantly lower for patients who initiated therapy on fluoxetine than for patients initiating therapy on sertraline. CONCLUSIONS: Broadly considered, the findings in this study suggest that total direct health care costs differ across initial antidepressant selection after controlling for both observed and unobserved characteristics.

Paroxetine. A pharmacoeconomic evaluation of its use in depression.

There has been intense debate about whether the use of paroxetine or other selective serotonin reuptake inhibitors (SSRIs) as alternatives to tricyclic antidepressants for first-line treatment of depression can be justified, considering their higher acquisition costs. The rationale for using paroxetine in the treatment of depression lies in its more favourable tolerability profile than tricyclic antidepressants and its lower risk of death on overdosage. Depression is one of the most common psychiatric disorders and is associated with substantial direct, indirect and intangible costs. Indirect costs account for the majority of costs associated with depression, while drug costs account for only 9 to 25% of direct costs. Therefore, increased recognition and treatment of depression has the potential to greatly reduce the overall cost of this disease. Pharmacoeconomic data on paroxetine and other SSRIs in the treatment of depression are scarce. Available studies are limited to considerations of direct costs alone and are primarily based on retrospective data from clinical trials. Nevertheless, in terms of costs per successfully-treated patient, available data suggest that the treatment costs associated with paroxetine are similar to those of amitriptyline and possibly less than those of imipramine. Paroxetine treatment costs also appear to be similar to those of amitriptyline and imipramine in terms of expected costs per patient. While one group of investigators suggested that the overall cost of administering paroxetine may also be less than that for fluoxetine and sertraline when drug costs and labour costs associated with dosage adjustment are taken into account, more data are required before conclusions on the relative pharmacoeconomic merits of SSRIs can be made. Despite the lower risk of death from overdosage with SSRIs, switching from an established tricyclic antidepressant to a newer tricyclic or related antidepressant in an attempt to avoid suicide appears to be more cost effective than switching to an SSRI. Thus, evidence available to date indicate that despite higher acquisition costs paroxetine and other SSRIs are no more costly than tricyclic antidepressants when total costs per successfully treated patient or expected costs per patient are considered. With its favourable tolerability profile and low risk of death on overdosage, paroxetine should therefore be considered as an effective alternative to tricyclic antidepressant agents as a first-line treatment of depression.(ABSTRACT TRUNCATED AT 400 WORDS)

Cost analysis of paroxetine versus imipramine in major depression.

A simulation decision analytical model was used to compare the annual direct medical costs of treating patients with major depression using the selective serotonin reuptake inhibitor (SSRI) paroxetine or the tricyclic antidepressant (TCA) imipramine. Medical treatment patterns were determined from focus groups of general and family practitioners and psychiatrists in Boston, Dallas and Chicago, US. Direct medical costs included the wholesale drug acquisition costs (based on a 6-month course of drug therapy), psychiatrist and/or general practitioner visits, hospital outpatient visits, hospitalisation and electroconvulsive therapy. Acute phase treatment failure rates were derived from an intention-to-treat analysis of a previously published trial of paroxetine, imipramine and placebo in patients with major depression. Maintenance phase relapse rates were obtained from a 12-month trial of paroxetine, supplemented from the medical literature. The relapse rates for the final 6 months of the year were obtained from medical literature and expert opinion. Direct medical costs were estimated from a health insurance claims database. The estimated total direct medical cost per patient was slightly lower using paroxetine ($US2348) than generic imipramine ($US2448) as first-line therapy. This result was sensitive to short term dropout rates but robust to changes in other major parameters, including hospitalisation costs and relapse rates. The financial benefit of paroxetine, despite its 15-fold higher acquisition cost compared with imipramine, is attributable to a higher rate of completion of the initial course of therapy and consequent reduced hospitalisation rates.