Acute and Continuation Treatment Adequacy With Venlafaxine Extended-Release Compared With Fluoxetin

Kristina S. Yu-Isenberg, Ph.D.; Christina L. Fontes, M.S.; George J. Wan, Ph.D.; Erika C. Geissler, R.N.; Ann S. M. Harada, Ph.D.


Pharmacotherapy. 2004;24(1) 

In This Article

Abstract and Introduction

Study Objective: To compare treatment adequacy in the management of depression during the acute and continuation phases between patients newly treated with venlafaxine extended release (XR) and those newly treated with fluoxetine.
Design: Retrospective observational analysis of pharmacy claims data.
Setting: Large California-based managed care organization.
Patients: A total of 11,298 patients newly prescribed venlafaxine XR or fluoxetine between January 1, 2000, and February 28, 2001, and continuously enrolled throughout the study, as well as a subset of 7430 patients who continued taking venlafaxine XR or fluoxetine during the follow-up period.
Measurements and Main Results: The Health Plan Employer Data and Information Set definition was used for continuous antidepressant treatment during the acute and continuation phases. Treatment adequacy was determined for those deemed continuous. Patients receiving within ±10% of the target dose for each drug (venlafaxine XR 75–150 mg, fluoxetine 20 mg) were defined as receiving an adequate dose. Logistic regression was used to evaluate venlafaxine XR versus fluoxetine on treatment adequacy, controlling for age, sex, physician specialty, and pharmacy benefit. The unadjusted adequacy rate for the venlafaxine XR–only group was 79% versus 57% for the fluoxetine-only group for 84 continuous days (p<0.0001) and 77% versus 52%, respectively, for 180 continuous days (p<0.0001). The adjusted odds ratios of achieving treatment adequacy with venlafaxine XR only versus that with fluoxetine only were 3.05 (95% confidence interval [CI] 2.65–3.52) for 84 continuous days and 3.57 (95% CI 3.00–4.24) for 180 continuous days.
Conclusion: Patients newly prescribed venlafaxine XR were at least 3 times more likely to achieve treatment adequacy for 84 and 180 days compared with those newly prescribed fluoxetine. Treatment adequacy as a proxy for optimal treatment may be an important factor to consider when selecting an antidepressant drug.

Depression is an affective disorder that is associated with significant morbidity, mortality, and health care costs. Approximately 19 million adults in the United States will experience a depressive disorder this year, and one in six persons in the United States will experience major depression at some point during their lifetime.[1] Among persons aged 65 years or older, the prevalence ranges from 10–20%.[2–4] Depression is 2–3 times more common in women and among those with a family history of mental illness. Moreover, adults aged 25–44 years experience the highest rate of depression.[2,5]

The economic burden of depression is considerable. Results of a study reported in 1993[6] indicated that the estimated cost of depression in the United States is approximately $44 billion annually. Of the total cost, 28% was attributable to direct medical and pharmacologic treatment, 17% for premature death, and 55% for work absenteeism and reduced work productivity.[6] Depression is one of the 10 most costly illnesses in the United States.[7]

Depression is undertreated, despite the high disease prevalence, cost, and availability of effective treatment modalities. An estimated 30% of patients seen in the primary care setting have significant depressive symptoms; however, the literature shows that more than half of these individuals will never seek medical treatment.[1,8] Moreover, even fewer patients (7%) receive adequate doses of antidepressant drugs.[2] There is overwhelming evidence that patients with depression are misdiagnosed, inadequately treated, or receive no treatment at all.[7–10]

The primary goal of depression treatment is remission of symptoms. In 1993, the Agency for Health Care Policy and Research (now known as the Agency for Health Care Research and Quality [AHRQ]) emphasized the need to reduce and ultimately eliminate depressive signs and symptoms as the initial objective of treatment.[11] This message was further underscored in the American Psychiatric Association (APA) practice guidelines for 2000, which highlighted remission as the goal of treatment.[12] The successful treatment of depression according to the APA guidelines consists of an acute phase, during which a remission is achieved; a continuation phase, in which the remission is preserved; and a maintenance phase, in which susceptible patients are protected from a recurrence of an episode of depression.[12]

Most studies of adequate antidepressant treatment have defined adequate treatment based on the 1993 AHRQ depression guidelines. Although these guidelines were appropriate at the time, they no longer are viewed as guidance for current medical practice, especially within health plans. Instead, a definition of adequate care in antidepressant drug management based on the standardized performance measures (Health Plan Employer Data and Information Set [HEDIS]) published annually by the National Committee for Quality Assurance (NCQA) are more applicable to decision makers in managed health care plans.[13] In 2000, the HEDIS summary statistics across participating health plans showed that 58.9% and 42.2% of patients received 84 and 180 continuous days of treatment with antidepressants, respectively.[13]

Venlafaxine extended release (XR) is a serotonin and norepinephrine inhibitor that has favorable remission[14,15] and similar tolerability and adverse-effect profiles as those of selective serotonin reuptake inhibitors (SSRIs).[16–18] Further, its ease of administration (once-daily dosing) helps to improve patient compliance and adherence to therapy. Previous studies, primarily clinical trials, have examined differences in efficacy and tolerability between fluoxetine and venlafaxine XR based on clinician-administered depression scales and adverse-effect profiles.[16–18] However, few studies have examined these outcomes in a large managed care population receiving antidepressant treatment in a usual care setting. Further, treatment adequacy of anti-depressants has not been described sufficiently by using HEDIS-derived quality indicators of depression management, specifically during the acute (84 days) or continuation (180 days) phases.

This study was conducted to provide additional evidence comparing treatment adequacy in depression management with venlafaxine XR versus that with fluoxetine, both administered once/day (a formulation that promotes better adherence), using HEDIS performance indicators in a naturalistic setting within managed care. The primary objective of this study was to compare acute and continuation treatment adequacy between patients newly treated with venlafaxine XR and those newly treated with fluoxetine.


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