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Assessment of Canadian Provincial Expenditures in Depressed Patients Treated With Venlafaxine XR Versus SSRIs: the APEX Study

Posted on: Thursday, 9 February 2006, 06:00 CST

By Monfared, A A Tahami; Han, D; Sheehy, O; Bexton, B; LeLorier, J

Key words: Antidepressants * Depression * Direct medical cost * Drug utilization * Persistence * Selective serotonin reuptake inhibitors (SSRIs) * Venlafaxine

ABSTRACT

Objective: Empirical studies of antidepressant cost- effectiveness suggest that the use of venlafaxine may be no more costly than selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression. The objectives of this study were to identify patients' characteristics and factors associated with the choice of antidepressant and to assess differences in persistence, healthcare utilization and direct medical costs associated with venlafaxine and SSRIs pharmacotherapy.

Research design and methods: We examined demographic and clinical characteristics of patients (n = 17144) who received both a diagnosis of depression and a prescription for venlafaxine or an SSRI between 1996 and 2004 using the Quebec health administrative databases. Logistic regression models were used to identify factors independently associated with the choice of antidepressant. Persistence to treatment and overall direct medical costs during 12 months after initiation of therapy were assessed using Cox proportional hazard and GLM models, respectively.

Results: Age, sex, provider specialty, and prior 12-month healthcare utilization significantly influenced initial antidepressant choice. Fewer venlafaxine-treated patients discontinued their initial therapy relative to SSRIs' (persistence to initial treatment: 38.4% vs. 29.4% and 24.4% vs. 15.8% at 6 and 12 months, respectively; p < 0.0001), and they were less likely to require treatment switching. Overall 12-month direct medical costs for SSRI- and venlafaxine-treated patients were Can$2759 and Can$2604, respectively. Patients treated with SSRIs had significantly higher expenditures in a univariate analysis (cost ratio: 1.06 [95% Cl: 1.02, 1.10]). However, after controlling for potential confounding factors such as patients' characteristics, prior healthcare utilization, and comorbid conditions in multivariate analyses, the overall expenditures were similar in both groups (cost ratio: 1.03 [95% Cl: 0.99, 1.07]).

Conclusions: Direct medical costs were generally similar among patients with depression treated with venlafaxine and SSRIs. In a 'real world' setting, the higher acquisition cost of venlafaxine is offset by savings due to fewer hospitalizations and fewer outpatient medical visits. Differences in treatment persistence may also, in part, explain the observed differences in average direct medical costs between venlafaxine and SSRIs.

Introduction

Depression is a highly prevalent chronic disease affecting 8% to 12% of individuals worldwide at some point in their lives1; the 1- year prevalence rate of depression in Canada is 4.1% to 4.6%2. Depression is often underdiagnosed3, undertreated3'4 and associated with significant morbidity, mortality, and healthcare costs5-7. The economic costs of depression are staggeringly high. In 1998, the annual direct and indirect medical costs of depression in Canada were Can$14.7 billion8.

Pharmacotherapy constitutes the main basis of the treatment of depression and its appropriate use is key to reducing the societal and economic burden of depression9. The clinician has a choice among several options, mainly: the tricyclic antidepressants (TCAs), the selective serotonin reuptake inhibitors (SSRIs) and venlafaxine, the first in a new class of drugs known as serotonin norepinephrine reuptake inhibitors (SNRIs). Several studies on the overall healthcare utilization of antidepressant therapy have demonstrated that SSRIs are more cost-effective than TCAs10-13. In addition, pharmacoeconomic analyses have demonstrated the incremental cost- effectiveness of venlafaxine relative to SSRIs as first-line therapy for depression14-16.

Limited 'real world' analyses, however, have been conducted to compare these drugs as first-line therapies for depression. Based on a retrospective, longitudinal study, Wan et al. compared the United States healthcare expenditures over a 6-month period among patients initiating treatment with either an SSRI or venlafaxine (immediate and extended-release oral formulations) as first-line antidepressants17. They found that in the 6-month period after initiating treatment, venlafaxine was associated with lower hospitalization expenditure for non-mental illness relative to SSRIs, although total healthcare expenditure was not significantly different. In addition, they found that venlafaxine was associated with a 50% decrease in the odds of hospitalization for non-mental illness compared with SSRIs, with significantly lower inpatient expenditure. Since this study was done from a US payer's perspective, and given the major differences between the US healthcare system and the Canadian healthcare system (a 'single payer system', in which healthcare is paid for and organized by the government), we decided to undertake a retrospective Canadian database study. The primary objective of this study was to assess the 12-month healthcare utilization and direct medical costs associated with the treatment of depression in patients initiating therapy with either venlafaxine or an SSRI. Since depression care is usually multifaceted, we additionally examined factors that might alter the cost of treatment, including patients' characteristics, persistence to initial antidepressant treatments, and factors affecting the initial drug choice between venlafaxine extended release (XR) and an SSRI.

Patients and methods

Study design

We conducted a retrospective population-based analysis of the Quebec provincial health administrative databases to measure the differences in patients' demographic and clinical characteristics, factors influencing drug choice, and overall direct medical costs during the study period. International Classification of Diseases (9th revision) Clinical Modification (ICD-9-CM) and Quebec Formulary Drug codes were used to identify eligible patients17-19.

Data source

In the Canadian province of Quebec, the Rgie de l'Assurance Maladie du Qubec (RAMQ) is the government body responsible for the administration of a universal health insurance plan and all physicians work within this system. Under this provincial plan, all Quebec residents are covered for medical services provided in hospitals or private clinics. A cost-sharing drug insurance plan covers residents aged 65 years and older, welfare recipients, as well as employed individuals (including dependents 18 years old and under) who do not have access to a private group insurance.

Information on demographic characteristics (e.g., age and sex) and dates of coverage are provided in a beneficiary file. Medical claims captured by the RAMQ contain information on all medical visits, including the date and nature of medical service, diagnosis (based on ICD-9-CM codes), medical procedures, physician's specialty, location of medical service provided (i.e., inpatient or ambulatory services), and the amount of reimbursement for that claim. Each record in the pharmaceutical claims database contains information on all outpatient-dispensed prescriptions, including drug name, date of dispensation, quantity, strength and dosage form, duration, the dispensing pharmacy and the prescribing physician, as well as the amount of reimbursement for the prescription, dispensing fees, and the copayment. Drugs dispensed to patients during stays in hospitals or public nursing homes, and overthe-counter drugs are not included in this database. The RAMQ pharmaceutical claims databases have been validated and are considered comprehensive and accurate20.

Study population

From the RAMQ, we obtained medical and pharmaceutical claims, as well as demographic records of a 25% random sample (n = 125000; rounded to the nearest 1000) of all patients who, between January 1, 1996 and March 31, 2004, had at least one dispensed prescription of an SSRI (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) or venlafaxine.

Venlafaxine immediate release (IR) was discontinued from the Canadian market on August 19, 2004. The study population was selected as a cohort of patients who, between May 1, 1998 (the date of the first dispensation of venlafaxine extended release (venlafaxine XR) in the source population) and March 31, 2003, had newly started their antidepressant therapy with one of the study drugs. The date of the first dispensed prescription for each patient was identified as the index date. Patients included in the analysis were required to have a diagnosis for depression within a 60-day period before the index date. ICD-9-CM codes used for a diagnosis of depression were as follow: 296.2 (major depressive disorder, single episode), 296.3 (major depressive disorder, recurrent episode), 300.4 (neurotic depression), 309.0 (brief depressive reaction), 309.1 (prolonged depressive reaction), and 311.x (depressive disorder, not elsewhere classified). All patients included in the cohort were required to have continuous healthcare coverage and observational periods of at least 12 months both before and after the index prescription to thoroughly examine the course of antidepressant therapy. Patients were excluded if, during the 12 months before the index date, they had a dispensed prescription for a lithiu\m medication, an antipsychotic medication, an ICD-9-CM code indicating bipolar disorder or schizophrenia, were younger than 18 years at the index date, or were not continuously enrolled in the health plan during the entire study period.

Study variables and measurements

The demographic characteristics of patients and their baseline comorbidity measures were assessed and compared between the study groups. Baseline comorbidity measures were evaluated by means of medical expenditures incurred during the 12 months prior to the initiation of antidepressant therapy, as well as the chronic disease score (CDS). The estimated 12month prior medical expenditures were the number of hospitalizations, inpatient length of stay (LOS), and number of medical visits to general practitioners, specialists, and emergency rooms (ERs) in both mental and non-mental institutions. The CDS was calculated on the basis of dispensed prescriptions in the year preceding the index date weighted for disease classes21,22. Prior medical expenditures and CDS have been used in previous economic studies to adjust for underlying differences in comorbidity and severity of illness22-24. The probable association between these measures and the choice of initial antidepressant medication was further explored.

The study of duration of treatment episode (persistence) requires that periods of continuous treatment be defined. The status of patients' adherence to antidepressant therapy was categorized as switching, discontinuation, or persistence, in that order. The index date of an initial prescription (index drug) was recorded for each patient. If a prescription was filled for an antidepressant other than the index drug within 1.5 times the number of days supplied (i.e., duration between the two consecutive prescriptions did not exceed the amount of time covered by the first prescription plus a grace period of 50% to allow for irregularities), the patient was classified as switched. If the prescriptions were not filled within the same period, the patient was classified as discontinued. If therapy was not switched or discontinued after the first prescription, the second prescription for the same drug was checked, and so on, until one of the following: switching or discontinuation was identified, the study end date, or the date that the patient's RAMQ drug insurance coverage ended (disenrollment date). If study drugs were switched, the dispensing date of the new prescription was recorded as the switch date. If therapy was discontinued, the dispensing date plus the number of days supplied was recorded as the discontinuation date. A patient was classified as persistent if therapy was not switched or discontinued. The study end date or the disenrollment date, whichever came first, was recorded as the persistence end date for patients classified as persistent. In addition, compliance rate was defined as the number of days that the study drugs were supplied in a pre-defined time window (i.e., 6 or 12 months) after the index prescription.

Direct medical costs per patient (in Canadian dollars, Can$) for the 12-month period following the index date for an SSRI or venlafaxine XR was calculated for inpatient25,26, outpatient27,28, and pharmaceutical29 expenditures. Inpatient costs were estimated using the 1994-95 financial data for all short-stay hospitalizations; which were adjusted to correspond to the average cost of hospitalizations in the province of Quebec for the year 2002 (Can$899.47). An index was calculated for each psychiatric hospitalization and was applied to the average cost of hospitalizations to establish its relative cost (Can$815.46). This index, reflecting the relative use of resources for each hospitalization, is classified according to the All-Patient Refined Diagnostic-Related Group (APR-DRG)30. The relative costs are based on diagnosis, severity and probability of poor outcome on groups of clinically homogeneous patients requiring an equivalent level of resources.

The direct medical costs also accounted for pharmaceutical services (including drug costs, dispensing fees, and copayments], outpatient visits to physicians, specialists, and ER visits at both mental and nonmental institutions. The costs of pharmaceutical services were directly obtained from the RAMQ database. The average cost estimates for a physician visit vary, depending on the medical specialty, from Can$42.50 for a general practitioner to Can$103.30 for a psychiatric visit; whereas the average cost per ER visit is estimated to be Can$116.97 for a non-mental institution and Can$206.17 for a mental institution27,28. Outpatient claims for antidepressants, sedatives, and hypnotics were also included as healthcare payments and further contributed to the average total cost per patient. The costs of medications not affecting the central nervous system (non-CNS drugs] were not included in the cost analyses; however, all estimates were controlled for the prior use of different types of medications by means of chronic disease score (CDS).

Statistical methods

Analyses were performed using the SAS software, v8.2 (SAS Institute Inc, Cary, NC). Differences in baseline demographic and clinical characteristics between study groups were compared by using the Wilcoxon signedrank test, a nonparametric approach, for continuous variables and using contingency table analysis with the Chi-square test for categorical variables. Logistic regression was performed to examine factors associated with drug choice at baseline between the venlafaxine XR and SSRI groups, controlling for potentially confounding variables, including age, sex, prior 12month medical and pharmaceutical resource utilizations, provider specialty, and type of drug insurance plan. Odds ratios and confidence intervals (CIs) were calculated for each covariate.

Persistence to initial antidepressant therapy and cumulative discontinuation rates were analyzed using the Cox proportional hazard models. Parameter estimates were adjusted for potentially confounding factors. Compliance was calculated by dividing the number of days prescriptions were supplied by the total number of calendar days in a 6- or 12-month period after the index date.

Average direct medical costs per patient were estimated for both venlafaxine XR and SSRI groups using the medical and pharmaceutical expenditures during the 12 months after the initiation of therapy. Generalized linear models (GLMs) were constructed to test for differences in direct medical costs between the study groups using the treatment group as the only effect in the model (univariate analyses). Multivariate analyses were further performed to assess the treatment effect on direct medical costs while controlling for baseline covariates and prior 12-month medical resource utilizations. Independent covariates included in the final model were age, sex, prior 12-month expenditures (including, number of hospitalizations, inpatient LOS, and number of medical visits), chronic disease score (CDS), initial provider specialty, and type of drug insurance plan. Cost ratios and CIs were also calculated for each covariate.

GLMs were used for the analysis of cost data because they provide parametric methods of analysis where a variety of non-normal distributions can be specified and the way covariates act can be altered. Unlike the use of data transformation in ordinary least- squares regression, GLMs make inferences directly about the average (mean) cost31.

In our analyses, several models were explored to determine the best distribution function for the outcome variable (i.e., direct medical costs), as well as the link function that provided the best scale on which covariates were related to the outcome. Final selection of the covariates was based on the goodness of fit of the model (i.e., proportion of variance explained). Model assessment was also performed based on aggregates of residuals in determining appropriate functional forms of covariates and link function.

Results

Baseline characteristics and co-morbidity

A total of 17 144 patients with a diagnosis of depression who initiated antidepressant therapy with either venlafaxine XR (n = 3150) or an SSRI (n = 13 994) were identified using the 25% random sample of RAMQ patients (n = 125000). The baseline characteristics of the patients are summarized in Table 1. There were small but significant differences in the group age and sex. Patients in the venlafaxine XR group were slightly younger (47.2 vs. 50.4 years) and a larger proportion were males. Females comprised approximately two- thirds (65-70%) of the study population in either group. Almost one- half of the patients were employed full time; whereas elderly and welfare recipients each accounted for about one-quarter of the patients. The majority of index drugs were prescribed by general practitioners in both the venlafaxine XR (89.71%) and SSRI (87.77%) groups. The mean (SD) chronic disease score for venlafaxine XR and SSRI groups were 1.95 (2.77) and 2.16 (2.87), respectively.

Table 1. Baseline demographic and clinical characteristics of study population

Choice of medication

Clinician choice for prescribing venlafaxine XR appeared to depend on a number of patient demographic and clinical characteristics that are summarized in Table 2. Factors such as age group, sex, and the initial provider specialty (prescribing physician] at the index date were significantly correlated with the choice of venlafaxine XR in antidepressant therapy. More specifically, a larger proportion of venlafaxine XR-treated patients were relatively younger (18-64 years of age), males, and their therapy was initiated by a general practitioner (Table 2). In addition, proxy measures of healthcare resource utilization during one year prior to the index prescription (e.g. number of hospitalizations, outpatient visits, and the type of drug insurance coverage) also significantly influenced choice of venlafaxine XR.In contrast, other covariates, including CDS and the number of dispensed prescriptions one year prior to the index date, were not statistically significant.

Persistence and compliance

The adjusted Kaplan-Meier (KM) survival analysis (Figure 1) shows significant differences in persistence (defined as time to drug discontinuation or switching) to the initial antidepressant therapy between the two study groups at 6 and 12 months post-index date. The risk of discontinuation of antidepressant treatment was very high after initiation of therapy (i.e. in the first two months). Fewer venlafaxine XR recipients discontinued their initial therapy compared to an SSRI (persistence to treatment: 38.4% vs. 29.4% at 6 months; 24.4% vs. 15.8% at 12 months, respectively; p < 0.001). It may suggest that venlafaxine XR either had taken effect more quickly than SSRIs or had produced fewer side effects. Furthermore, patients initially treated with venlafaxine XR were less likely to require treatment switching during their therapies as compared to SSRIs (4.7% vs. 6.1%, respectively; p = 0.0025). The compliance rates at 6 (57.5% vs. 55.3%) and 12 months (50.3% vs. 47.0%) post-therapy were also significantly higher for venlafaxine XR (p < 0.001).

Medical resource utilization

Tables 3 and 4 summarize the average medical and pharmaceutical services consumption during one year before and after the index prescription, respectively. Small but statistically significant differences were found for the dispensation of a few co- medications, average inpatient length of stay (LOS), and outpatient visits during one year prior to the index date (Table 3). The average number of dispensed prescriptions for tricyclic antidepressants (TCAs) and Wellbutrin were slightly higher for the venlafaxine XR group, whereas the average number of dispensations for benzodiazepines was slightly lower. However, the utilization patterns were similar during the 12-months both preand post- therapy.

Table 2. Adjusted odds ratio for factors influence the initiation of therapy with venlafaxine XR1

Figure 1. Adjusted Kaplan-Meier survival curves representing persistence to the initial antidepressant therapy (i.e. time to discontinuation or switching from initial antidepressant therapy)

Table 3. Consumption of medical resources during 12 months prior to the index date

Medical resource utilizations one year after the initiation of therapy were also similar for both groups (Table 4). The only pronounced and statistically significant differences were found in the average inpatient LOS in non-mental institutions and outpatient visits to medical specialists (other than psychiatrists). The average LOS were 0.98 and 1.17 days (p = 0.02) for the venlafaxine XR- and SSRI-treated patients, respectively; the average outpatient visits to specialists was 3.82 and 4.16 times (p = 0.03) (Table 4).

Healthcare costs

The best-fitted generalized linear model (GLM) was found to be a model with a log link function for the patient direct medical costs providing multiplicative covariate effects and a gamma distribution as the error structure. Overall, the average 12-month direct medical costs of patients treated with SSRIs and venlafaxine XR after the initiation of antidepressant therapy were Can$2759 and Can$2604, respectively. Hospitalizations made up the largest single category of direct medical costs, while antidepressant medications accounted for less than 20% of the costs (Table 5). In our analyses, medication costs included drug acquisition costs, dispensing fees, and copayments. The average drug cost of venlafaxine XR was 25% higher than that of SSRIs (Can$425 vs. Can$340, respectively; p < 0.0001), largely due to the availability of generic SSRIs in Quebec during the study period. In contrast, in a univariate analysis, the average direct medical costs for patients treated with SSRIs were found to be 6% higher than venlafaxine XR-treated patients (cost ratio: 1.06 [95% CI: 1.02, 1.10]). However, controlling for baseline covariates and medical resource utilizations received during the 12- month period prior to the index date resulted in an adjusted cost ratio of 1.03 [95% CI: 0.99, 1.07], which was no longer statistically significant. In general, our study suggested that overall direct medical costs for patients who started antidepressant therapy with venlafaxine XR are similar to those who started therapy with an SSRI. This finding was robust to the sensitivity analyses performed where, (1) acquisition costs of only generic SSRIs were used to estimate medication costs in our study population while venlafaxine XR costs remained unchanged; and (2) actual costs of SSRIs in the RAMQ database were used while the cost of venlafaxine XR was increased up to 15% of its actual price in a threshold analysis where the break-even point was reached.

Table 4. Consumption of medical resources during 12 months post- index date

Discussion

Depressive symptoms are associated with high healthcare utilization and costs32-34. Depression is also correlated with detrimental effects on role and physical functions even when controlling for comorbid medical conditions32. It may lead to poor self-care or poor persistence to medical treatments that in turn, adversely affect health and thereby increase healthcare costs34. Previous studies have shown that providing effective care for depression may lead to a decrease in the healthcare utilization (especially non-mental health) and consequent costs34, as well as an improvement of patient physical functioning32. An important challenge in an observational study of the treatment of depression is to determine patients' characteristics, factors affecting drug choice, and determinants of medical care cost consequences of providing mental health interventions. A retrospective populationbased study was therefore performed to evaluate the aforementioned factors associated with the treatment of depression in patients initiating therapy with either venlafaxine XR or an SSRI.

In our study, the characteristics of patients started on an SSRI or venlafaxine XR allowed us to estimate the key parameters in the 'channeling' of these medications. Venlafaxine XR was more likely to be considered the initial drug of choice for patients younger than 65 years old, who previously suffered from a number of other comorbid conditions. The working population was also more likely to receive venlafaxine XR than individuals on welfare or the elderly. The pattern that emerges from these data is that venlafaxine XR was channeled towards patients aged 18-64 years with higher comorbidities. In a retrospective longitudinal study of the US MEDSTAT database which contains claim data for 3.2 million American people working for 40 large employers, Wan et al. also found that venlafaxine XR was channeled to patients with higher co- morbidities17.

Table 5. Expenditure of medical resources during 12 months post- index date (crude and adjusted estimates) in Canadian dollars, Can$

The effectiveness of pharmacotherapy has often been defined by the ability of patients to tolerate and comply with the medication regimen for a specified length of time. When patients take drugs appropriately, the likelihood of achieving good health outcomes is high. To the contrary, when they are not persistent, the health outcomes can be jeopardized. In general, optimal therapy for depression requires a minimum of 6-8 weeks for the acute phase, followed by 4-9 months for the maintenance phase once the symptoms have resolved9,35-38. Considerable research has demonstrated reductions in recurrence and relapse rates39 and reduced functional disability40 from longer lengths of treatment in the acute phase of depression. However, examining the persistence to antidepressant therapy in our study indicated that up to 55% of patients within the first 3 months and as many as 70% within 6 months of treatment initiation discontinued their medication (Figure 1). The results of our study are consistent with those of previous studies documenting suboptimal treatment duration, in which the average duration of antidepressant therapy was reported to be less than 3 months; most patients were not treated adequately and they discontinued medication within 6 months of starting treatment41-45.

Switching and discontinuation of therapy probably occurred for a variety of reasons, such as adverse effects and lack of efficacy45,46. As shown in Figure 1, a significantly better persistence to therapy was found in patients treated with venlafaxine XR as compared to SSRIs (p < 0.0001). Although we could not identify the reasons for switching or discontinuation in our retrospective study using claims databases, quantitative description of persistence in our sample population indicates either better effectiveness or improved adverse effects profile for venlafaxine XR.

Using the persistence curve and calculating 'percent wasted patients' (PWP)47, defined as the percentage of patients who have discontinued therapy before the time point at which clinical benefits were expected, also provided an opportunity to determine the waste of resources in our treatment groups47. As a group, patients who were not persistent to treatment beyond this time point (i.e., a minimum of 6 months for the treatment of depression) could not benefit from the intervention and represented a waste in terms of the health resources spent on their pharmacological therapy, physician visits, and hospitalizations. They also represented an opportunity cost in terms of the outcomes that would have been prevented had they remained on therapy. As shown in Figure 1, the PWP of the SSRI-treated patients is approximately 10% higher than the venlafaxine XR-treated group at 6 months post-therapy, indicating a larger potential for waste in healthcare resources.

On average, shorter inpatient LOS in non-mental institutions and fewer medical visits were found in the venlafaxine XR gro\up. Treatment of depression with venlafaxine XR may, in part, be responsible for these reductions. The 2002 Report on Mental Illnesses in Canada stated that, in 1999, among people under the age of 50 years with major depressive disorder who were hospitalized, the disorder was the main contributor in determining their length of stay48. However, among people with the disorder over the age of 50 years, depression was more likely to be an associated condition contributing to the length of stay48. Although this is consistent with the association between physical illness and depression, further research is required to determine the reasons for this trend. Many factors other than the prevalence and severity of illness can influence hospital admissions and lengths of stay. Moreover, as patients age, many will develop symptom profiles that strongly suggest subsyndromal or atypical forms of depression, some due to medical conditions or general frailty.

The higher persistence to therapy, as a proxy for treatment effectiveness and overall patient satisfaction49-51, might in part be responsible for reducing hospitalizations in patients treated with venlafaxine XR. It also corroborates the results of two independent meta-analyses of randomized clinical trials which showed higher remission rates in patients treated with venlafaxine XR than patients treated with SSRIs52,53.

By comparing the resource utilizations such as hospitalizations and medical visits that occurred before and after the initiation of the drugs of interest, we were able to compare the direct medical costs incurred by the patients in the two groups in a 'pre-post' design. In spite of the fact that the study drug expenditures were significantly higher in the venlafaxine XR group, largely due to the costs of generic SSRIs, the overall direct medical costs were similar in the two groups. This similarity was more evident in the final model where the direct medical costs per patient were adjusted for all baseline covariates and prior 12-month medical expenditures; no significant difference was found between the two treatment groups. The higher acquisition cost of venlafaxine XR was thus offset by savings elsewhere in the healthcare system. The main driver of these savings was the lower average hospitalization expenditures: Can$2081 for venlafaxine XR-treated patients and Can$2324 for the SSRI-treated patients (p < 0.02). Our results are similar to the findings of Wong and Bymaster54 and Poret et al.55, who also found that the total healthcare costs for the patients initiating therapy with venlafaxine XR were similar to those of the patients who were initiating therapy with SSRIs. The lower hospitalization costs in the venlafaxine XR group may reflect a higher effectiveness of this drug in achieving and sustaining remission of depression53,56.

Several limitations must be considered for this study. The first limitation is the absence of clinical data on subjects receiving antidepressant medications. Patients who received antidepressants did not have confirmation of diagnosis by standard rating techniques. Antidepressants could be indicated in the treatment of psychiatric disorders other than depression and/or to control non- psychiatric symptoms; however, the database did not allow a distinction to be made between these conditions. Some unknown fraction of patients may have been prescribed antidepressants for pain, insomnia, or other conditions where guideline concordance is not relevant. This fraction, however, is likely to have been small because patient selection required an ICD-9-CM diagnostic code of depression. Several studies suggest that false-positive diagnosis of mood and anxiety disorders is rare57, and that a substantial majority of patients prescribed antidepressants in routine general medical settings have a mood or anxiety problem for which guidelineconcordant treatment is indicated58. In addition, the lack of data on whether patients eventually took the prescribed medications should be highlighted, since around half of the medicines prescribed for people with chronic conditions are not taken59. Furthermore, since our study was limited by the variables measured in the RAMQ databases, we could not directly assess some potentially important confounders, including smoking, alcohol consumption, body mass index, and severity of primary illness.

Despite its limits, the study approach retains a major strength of claims-based analyses, namely, superior statistical power. Our study made it possible to include the large number of patients typically excluded from prospective studies60 and provided an assessment of patterns of antidepressant use under 'real world' conditions.

Conclusion

Consistent with findings in other studies, using different populations with patients treated in different healthcare systems, our results clearly show that in 'real world' settings the higher acquisition cost of venlafaxine XR is offset by savings due to fewer numbers of hospitalizations and lower utilization of health services. The results must be viewed with caution, however, since residual bias may have persisted despite the adjustment for baseline covariates and prior 12-month medical and pharmaceutical resource utilizations in our analyses.

Acknowledgments

Declaration of interest: This study was supported by an unrestricted grant provided by Wyeth Pharmaceuticals, Canada. The funding agreement ensured the authors' independence in designing the study, interpreting the data, and disseminating and publishing the reports and manuscripts.

The authors would like to thank Mrs Anita Massicotte for excellent secretarial assistance with the manuscript submission.

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CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com

Paper CMRO-3243_3, Accepted for publication: 08 November 2005

Published Online: 22 November 2005

doi:10.1185/030079906X80314

A. A. Tahami Monfared (a,b), D. Han (c), O. Sheeny (a), B. Bexton (d) and J. LeLorier (a)

a Pharmacoepidemiology and Pharmacoeconomics Research Unit, Centre de Recherche, Centre Hospitalier de l'Universit de Montral (CHUM), Campus Htel-Dieu, Montreal, Quebec, Canada.

b McGill University Health Center, The Montreal General Hospital, Montreal, Quebec, Canada

c Wyeth Pharmaceuticals, Markham, Ontario, Canada

d Clinique des maladies affectives, Hpital du Sacr-Coeur, Montreal, Quebec, Canada

Address for correspondence: Dr Jacques LeLorier, Centre de Recherche, Centre Hospitalier de l'Universit de Montral, Htel-Dieu, Pavillon Masson, 3850, rue Saint-Urbain, Montreal (QC), Canada H2W 1T7. Tel.: +1 514-890-8000, Ext 14080; Fax.: +1 514-412-7174; email: massicoa@umontreal.ca

Copyright Librapharm Jan 2006

Source: Current Medical Research and Opinion

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