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


This study was a retrospective observational analysis of pharmacy and enrollment administrative claims data.

Data used for this study were from a large California-based managed care organization and from Prescription Solutions (Costa Mesa, CA), a pharmacy benefit management organization subsidiary of the managed care organization. We used longitudinal claims data from California, Oklahoma, Oregon, Texas, and Washington, which consisted of approximately 3.5 million member lives. All claims were uploaded monthly to a central data warehouse and underwent quality assurance edits. This database has been used in previous health care services and economic studies.[19–21] We examined electronic pharmacy and enrollment claims from October 1, 1999–November 30, 2001.

Using pharmacy claims, we identified two distinct samples of patients: those newly started on fluoxetine and those newly started on venlafaxine XR during the index period, January 1, 2000–February 28, 2001. The date of the first fill of either fluoxetine or venlafaxine XR was defined as the index date. Patients were followed for 90 days before and 270 days after the index date to examine adequate trial of therapy. For both cohorts, patients were excluded from the study if they were younger than 18 years at the index date, were not continuously enrolled in the health plan during the entire study period (90 days before and 270 days after their index date), or had filled a prescription for fluoxetine, venlafaxine or venlafaxine XR, citalopram, paroxetine, or sertraline 3 months before the index date.

Treatment adequacy was the primary outcome of interest. Treatment adequacy was examined in a subset of patients who were treated exclusively with either venlafaxine XR or fluoxetine during the follow-up period. Continuous trial of therapy was defined by using the HEDIS (year 2000) performance measures related to antidepressant drug management.[13] The intent of these HEDIS measures is to assess different components of the successful pharmacologic management of depression, which include effective acute- and continuation-phase treatment for 84 and 180 days, respectively. Response to antidepressant therapy was measured by the proportion of patients with continuous treatment for 84 and 180 days, using HEDIS-derived criteria. Continuous treatment with the index antidepressant drug was calculated by adding the number of days supply of all prescriptions with service dates within 114 days (84-day measure) or 231 days (180-day measure) of the index date. If the total days supply was at least 84 and 180 days with gap days below 30 and 51 days, respectively, patients were assumed to have 84 and 180 days of continuous treatment. A gap in therapy was defined as the number of days between the fill date plus days supplied and the date of the next prescription fill.

With the HEDIS definition of continuous trial of therapy as the foundation, adequate trial for 84 days was calculated by determining adequate dose for each antidepressant drug filled within 114 days of the index date for members determined continuous. If the days supply for each antidepressant drug filled at adequate dose totaled at least 84 days, then the patient was deemed to be receiving adequate trial for 84 days. Similarly, the adequate trial for 180 days was calculated by determining adequate dose for each drug filled within 231 days of the index date. The average daily dose was calculated as strength multiplied by the quantity supplied divided by days supplied. Similar to the algorithm used in a previous study,[22] dose levels were considered adequate if they were within 10% of the dose standards previously defined[23]: 75–150 mg for venlafaxine XR and 20 mg for fluoxetine.

Demographic variables were age, sex, and product line (commercial health plan or Medicare+Choice) at index date. The specialty of the antidepressant prescriber was classified into the following three categories: "psychiatry" including addiction psychiatry, adult or child psychiatry, geriatric psychiatry, or psychiatry; "other" including all specialties except psychiatry; and "undetermined" if the specialty of the prescriber was not listed in the professional reference table, which was found in about 30% of the cases. Pharmacy benefit design type was determined from either medical claims or employer identification from the membership enrollment information. Three categories of pharmacy benefit design were represented: "open design" included a comprehensive list of drugs with reimbursement for all drugs prescribed; "managed design" included a list of drugs that were labeled as formulary or nonformulary, and "three-tier plan" covered formulary and nonformulary drugs with increasing copayments. Drug-related variables were measured by number of days supply, strength, and quantity.

Differences in demographic and other characteristics between study cohorts were compared by using the t test for continuous variables and χ2 test for categoric variables. The Fisher exact test was used for instances when at least one cell size was less than five. Logistic regression was performed to examine adequate dosage at 84 and 180 days between the fluoxetine-only and venlafaxine XR–only groups, controlling for confounding variables such as age, sex, provider specialty, and pharmacy benefit. Odds ratios and confidence intervals (CIs) were calculated for each covariate.

Due to extreme outliers, two pharmacy claims that met the following criteria were excluded from the analysis: a venlafaxine XR claim with daily dose greater than 800 mg, and a fluoxetine claim with daily dose of 600 mg or greater. In addition, one member with a claim for a days supply of 2 was changed to a days supply of 30, based on historic pharmacy claims data. No other outliers were detected.


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