Costs of Antidepressant Medications Associated With Inadequate Treatment

Published Online: June 01, 2004
Jeffrey B. Weilburg, MD; Randall S. Stafford, MD, PhD; Kathleen M. O??Leary, BA; James B. Meigs, MD, MPH; and Stan N. Finkelstein, MD

Objective: To determine the costs of antidepressant medications used during inadequate treatment.

Study Design: Retrospective database analysis of pharmacy claims made by patients who were treated under routine clinical conditions from July 1, 1999, through September 30, 2002.

Patients and Methods: Our participants included 21 632 patients enrolled in a commercial HMO who had a primary care physician associated with our healthcare system. Patients never receiving at least a minimum likely effective antidepressant dose for at least 90 days were defined as having inadequate treatment. This study calculated the costs of antidepressants involved with inadequate treatment at the level of the patient and the medication trial.

Results: A majority of patients (51%) received inadequate treatment. Of overall antidepressant costs, 16% were incurred during trials for patients never adequately treated. The majority of inadequate trials were short and unlikely to have been effective. Most patients (64%) had only a single trial of antidepressants. Venlafaxine, fluoxetine, and sertraline had significantly lower firsttrial inadequacy rates compared with the most commonly prescribed agent, citalopram.

Conclusions: Improved patient care quality and lower antidepressant costs could result if clinicians and healthcare systems focus on reducing short trial rates. Initiating treatment with agents least likely to be discontinued prematurely may be helpful.

(Am J Manag Care. 2004;10:357-365)

Antidepressants are among the most frequently prescribed medications in the United States, accounting for approximately 14% of the total US outpatient pharmacy costs in 2000.1 Antidepressant use rates and costs are projected to increase throughout the coming decade,1 driven in large part by the increasing recognition and treatment of both mood and anxiety disorders by physicians in general medical settings.2 Despite the high frequency of antidepressant use, concerns have been raised regarding the effectiveness of current prescribing practices.3-6

The goals of antidepressant treatment for mood disorders are full remission of symptoms and prevention of relapse. Doses need to be sufficient to produce symptom resolution, and treatment needs to continue for a sufficient duration (4-12 months beyond symptom resolution) to reduce the likelihood of relapse.7-13 Courses of treatment failing to meet these targets are likely to be suboptimal and can be regarded as inadequate treatment trials.4,10,14-16

Treatment goals for the use of antidepressants in patients with anxiety disorders are very similar, and guidelines for anxiety disorders have minimum dose and duration targets5,17-21 nearly identical to those in mood disorder guidelines. Mood and anxiety symptoms frequently appear together in patients in general medical settings,22-25 and primary care physicians (PCPs) base decisions to use antidepressants more on symptom severity than on diagnosis.26,27 Because underdiagnosis and undertreatment of mood and anxiety disorders are common,3 and rates of false-positive diagnosis by PCPs of mood, anxiety, and other mental disorders are relatively low,26 provision of antidepressant medication for patients without an appropriate indication is unusual.28 These factors argue in favor of including a broad spectrum of patients receiving antidepressants when undertaking an assessment of antidepressant treatment.

Rates of inadequate antidepressant treatment are high in part because many patients discontinue treatment early.6,13,14,29-32 Little attention has been devoted to the costs incurred by healthcare systems and HMOs in payment of pharmacy claims made by covered patients who use antidepressants for short, inadequate courses of treatment.33,34 We hypothesized that a large fraction of the total acquisition cost of antidepressants was associated with treatment considered inadequate due to premature discontinuation. To evaluate this hypothesis, we conducted a retrospective analysis of antidepressant use patterns and their associated acquisition costs for patients prescribed antidepressants in a large HMO.


Data Source

We analyzed pharmacy records from an HMO from July 1, 1999, through September 30, 2002. Patients in this dataset had a PCP in the Partners HealthCare System, a network of academic and community PCPs and specialists in Eastern Massachusetts.

No formulary restrictions, mental health carve-out, or depression management program impacted the study population during the time the data were collected. There was a 3-tier drug copayment program. This program varied by employer; but in general, during 2002, most patients paid $5-$10 per month for generic antidepressants, which were in the lowest tier; $20 for most other antidepressants; and $35 for weekly brand-name fluoxetine, the only antidepressant in the top tier.

Prescription records showing the fill date, drug name, dose, number of pills supplied, and name of prescriber from retail and mail order pharmacies were collected. After correction of data entry errors, 2.61 million prescription records for 161 132 patients with costs totaling $95.6 million were available for analysis.

A total of 26 414 patients (16.4% of the patients in the database) received 230 924 antidepressant prescriptions (8.9% of total prescriptions). These antidepressant prescriptions totaled $16.0 million (17.0% of total pharmacy costs for all medications). Copayment costs incurred by patients were unavailable; hence, they were not included in this analysis.


An individual treatment trial was defined as 1 or more continuous prescriptions of the same antidepressant. If a gap of more than 120 days between prescriptions occurred, a new trial was considered to have begun unless the prescription written before the gap provided sufficient days of medication therapy to bridge the gap period.

Tricyclic antidepressants (TCAs) and trazodone in low doses are commonly used for treatment of chronic pain, insomnia, and other conditions for which mood disorder guideline concordance is not relevant. We eliminated the 5584 trials involving only low-dose TCAs or trazodone, excluding 2572 (9.7%) patients. The excluded trials represented only $47 200 or 0.3% of all of the antidepressant pharmacy costs. Table 1 lists the low-dose thresholds.

Data on enrollment duration were available for most members (99.1%) in the database. When we did not have enrollment data, we used pharmacy fill dates as proxies for enrollment periods. Patients without evidence of more than 180 days of membership in the plan were eliminated from the analysis.

Final Analytic Sample

After excluding low-dose TCA and trazodone trials and patients with short enrollment periods, 21 632 patients remained for analysis. A total of 203 081 antidepressant pharmacy records remained; the corresponding total cost of the medication was $15.6 million.

Definition of Treatment Inadequacy

Treatments that failed to achieve use of minimum likely effective doses and/or were prematurely discontinued were defined as inadequate. The minimum likely effective dose for each agent (Table 1) was derived from literature review and practice guidelines.12,35 To make comparisons between agents, all antidepressants were first adjusted to a "fluoxetine equivalence" based on equating their minimum daily dose as displayed in Table 1 to 20 mg of fluoxetine. We then examined patterns of use. The distribution of actual mean daily dose based on an expected use of 20-mg fluoxetine equivalents per day showed a close clustering between 18.75 and 20 mg/day. A mean daily dose of approximately 18.75 mg is achieved if patients miss 2 daily doses in a 30-day period. We set the minimum threshold for dose adequacy at 18.75 mg of fluoxetine equivalents per day, as this allowed patients with less-than-perfect adherence still to be considered as receiving an adequate dose, while also reflecting the gap between this pattern of use and the cluster reflecting use of lower doses.

We examined every period within a trial, beginning and ending with a prescription fill date, and calculated the average daily dose and the cumulative length of the trial for each of these periods, looking for at least 1 90-day period during which our minimum daily average dose was achieved. Thus, patients could have a period of dose titration at the beginning of a trial and still achieve adequacy by having at least 90 days in the middle of the trial during which they received an adequate dose. The last prescription in a trial was used only to indicate the date by which the medication in the previous prescription had been consumed. Pills dispensed in the final prescription were not included in our calculations because we could neither assume that all of these pills were consumed, nor know the time period it took for their consumption. Patients with more than 1 treatment trial were considered to have had adequate treatment if any 1 of their trials met adequacy criteria.

Patients were divided into 2 groups: those who received at least 1 period of adequate treatment and those who never received adequate treatment. All of the trials for patients who never received adequate treatment are grouped into "all trials for inadequately treated patients" (Table 2). In contrast, "all trials for adequately treated patients" included some inadequate trials. This is because patients with adequate treatment may have had some trials that were inadequate. For example, a patient may have had a short trial, been switched to another agent, and had an adequate trial of the second agent. Within these 2 groups of patients, we stratified trials by trial duration.

Definition of Provider Type

Every pharmacy record specified the prescribing physician and patient's PCP. Prescribers were assigned to 1 of 3 categories: PCPs, psychiatric specialists, or "other." Others were nonpsychiatric specialists, hospital residents, unknown doctors, and those records with invalid and/or unidentified Drug Enforcement Administration numbers. Within the "other" category, the largest group was nonpsychiatric specialists (50.0%).

Analytic Methods

"No refill trials" involved only a single prescription. More than 82% of these single prescription trials were for fewer than 90 pills, and 50% of these prescriptions were for 30 pills or fewer. Trials between 0 and 90 days were defined as having at least 1 refill but no refills beyond a 90-day cutoff. Trials in this group were sufficiently below duration guidelines for mood and anxiety disorders that it was unlikely that treatment during these trials was effective.

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