Rate of non-adherence prior to upward dose titration in previously stable antidepressant users

Abstract

Background

Non-adherence to antidepressant medications is a contributing factor to disease relapse and may result in needless increases in antidepressant dosing.

Methods

We analyzed de-identified patient claims data from Medco Health Solutions, Inc.'s information database and measured adherence as the medication possession ratio (MPR), with adequate adherence as MPR ≥ 80%. Adherence was calculated for patients in whom antidepressants were dose escalated and who were on the same antidepressant medication for at least 180 days before the upward dosage titration. Statistical analysis was performed on subgroups comparing adherence with mail vs. retail channels, differences in age and gender, generic prescription vs. brand only, and prescription by psychiatrist vs. non-psychiatrist.

Results

29.7% of patients were non-adherent to their antidepressant medication during the 6 months prior to a prescribed increase in dosage. Non-adherence was significantly lower among patients using the Medco Therapeutic Resource Centers® mail order vs. retail channel. Younger age correlated with poorer adherence. Rates of non-adherence were also significantly greater among women, those receiving generic medications, and among patients with overall lower disease comorbidity. Adherence was not significantly impacted by prescription from a psychiatrist or a non-psychiatrist.

Limitations

Retrospective design and use of an administrative patient claims database.

Conclusions

Suboptimal medication adherence commonly precedes an upward dosage titration of antidepressant medications. Utilization of a mail order channel may improve adherence. Clinicians prescribing antidepressants should explore adherence issues carefully prior to recommending an increase in dosage.

Introduction

Patient adherence or compliance may be defined as the extent to which a patient's behavior conforms to medical or health advice (Bruer, 1982). The term ‘adherence’ has gradually supplanted ‘compliance’ in the literature for many reasons, perhaps primarily due to the notion that adherence refocuses responsibility on the patient–clinician therapeutic alliance rather than solely on the patient “complying” with doctors' orders. Clinicians may improve adherence to prescribed therapy through careful discussion with their patients about their illness and the rationale for the use of medication, asking about the patient's attitudes and fears regarding medication, and providing education concerning expectations for both improvement and possible side effects (Fawcett, 1995).

In the treatment of major depression, there is a broad consensus recommending continuation of antidepressant medication for at least 4 or more months yet a significant proportion of patients discontinue medication during the first several weeks of treatment (American Psychiatric Association, 2000, Geddes et al., 2003, Keller et al., 2002, Olfson et al., 2006). About one-third of patients in one primary care study discontinued antidepressant therapy within 1 month of initiating treatment and approximately one-half discontinued within 3 months (Simon et al., 1993). Elevated rates of early antidepressant discontinuation are not unique to primary care settings, having also been documented among cohorts of privately insured patients, Medicaid populations, managed pharmacy benefit plans, and psychiatric patients (Fairman et al., 1998, Katzelnick et al., 1996, Lewis et al., 2004, Melfi et al., 1998, Simon et al., 2001). Complicating matters further, depression itself is a risk factor for non-adherence with medical treatment (DiMatteo et al., 2000).

Large-scale, descriptive epidemiological studies of adherence in the treatment of depression report a wide range of adherence rates with a median of only 63% (Pampallona et al., 2002). However, these data are limited by the application of different measures of adherence including pill counts, blood levels of medication, behavioral indicators, psychological symptoms, and subjective reporting or adherence to a pre-defined schedule of appointments.

In a retrospective study of patients (N = 22,947) initiating selective serotonin reuptake inhibitor (SSRI) therapy for depression and/or anxiety in a large national managed care database, rates of 6-month SSRI adherence were measured by 3 different metrics: length of therapy (LOT), medication possession ratio (MPR), and combined MPR/LOT (Cantrell et al., 2006). The LOT was calculated as the number of days from the first prescription fill date to the ending date of the last prescription filled or 180 days, whichever occurred first. MPR was calculated as the sum of the days' supply of all SSRI medications within 180 days after the first fill date divided by 180 days. The hybrid MPR/LOT method measured the percentage of patients remaining on therapy for a minimum of 90 days without a 15-day gap while having an MPR of at least 80% over 180 days. Across all methods approximately 57% of patients were non-adherent to therapy. Differences in resource utilization for each adherence metric were measured for patients categorized into each of the following groups: adherent, non-adherent, therapy changers, and dose titraters. Regardless of metric, the adherent cohort incurred significantly less annual medical costs, followed by the non-adherent, titrate, and therapy change cohorts. The difference in annual medical costs between adherent and non-adherent patients based on MPR was $423 US dollars. When antidepressant prescription costs were added to medical costs, patients requiring a therapy change and titrating therapy incurred higher costs, whereas adherent patients, as measured by any method including the MPR, incurred the lowest annual medical costs.

Discrepancies have been reported between instructions; physicians claim they communicate to patients and what patients recall being told, including specific recommendations to continue taking antidepressants for at least 6 months (Bull et al., 2002). Explicit instructions about expected duration of therapy and discussions about medication adverse effects throughout treatment may reduce discontinuation of SSRI use. Bull and colleagues also found that patients with 3 or more follow-up visits were more likely to continue using the initially prescribed antidepressant medication, suggesting that frequent patient–physician contact may increase the probability that patients will continue therapy (Bull et al., 2002).

This study examines adherence rates preceding upward dose titration among patients on stable-dose antidepressant pharmacotherapy for ≥ 6 months prior to dose increase.