Elsevier

Clinical Therapeutics

Volume 35, Issue 4, April 2013, Pages 512-522
Clinical Therapeutics

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Original research
The Economic Burden of Treatment-Resistant Depression

https://doi.org/10.1016/j.clinthera.2012.09.001Get rights and content

Abstract

Background

Major depressive disorder (MDD) is a leading cause of disability, morbidity, and mortality worldwide. The lifetime prevalence in the United States is estimated at 17%. Treatment-resistant depression (TRD) is generally defined as failure to achieve remissions despite adequate treatment. About 30% of patients do not achieve remission after 4 different antidepressant treatment trials. A few studies have examined the economic burden of TRD, but none has investigated the cost associated with more chronic and extensive forms of TRD characterized by nonresponse to ≥4 treatment trials.

Objective

The objective of this study was to compare the health care utilization (HCU) and direct medical expenditures of TRD patients with those of chronic MDD patients.

Methods

Patients with chronic MDD (defined as ≥2 years of continuous treatment) and patients with TRD (defined as undergoing at least 4 different qualifying antidepressant therapy trials) were identified in the PharMetrics Patient-centric Database. The association between TRD and medical expenditures was measured by using multivariate regression analysis.

Results

The classification of TRD had a clinically meaningful and statistically significant association with increased medical expenditures. Holding all else equal, the classification of TRD was associated with a 29.3% higher costs (P < 0.001) in medical expenditures compared with patients not meeting the study definition of TRD.

Conclusions

These results demonstrate that TRD is associated with significantly higher per-patient medical costs due to higher HCU. The findings suggest that the development of treatment alternatives for TRD is warranted. Limitations related to the use of secondary administrative data are noted.

Introduction

The lifetime prevalence of major depression ranges from 1.5% to 19%.1 In the United States, the lifetime prevalence is ∼17%.2, 3 Major depression is associated with significant social, educational, and vocational impairment; high utilization of social and health care services; and increased medical morbidity and mortality.1, 4

The goal of therapy should be the absence of significant depressive symptoms with complete recovery from impaired function.5 With any first-choice antidepressant, ∼50% to 70% of patients will have a significant response (usually defined as a ≥50% decrease in depressive symptoms). Of these responders, one half to one third achieve full remission. Hence, a significant proportion of patients with depression have residual or persistent symptoms despite apparently adequate antidepressant therapy. Treatment-resistant depression (TRD) is defined as the failure to achieve full remission with an antidepressant used at an adequate dose and duration.6 When patients do not achieve a satisfactory response despite adequate therapy, the 2 basic strategies are switching or adding an antidepressant to the regimen.7 Failure to achieve remission with antidepressant therapy is associated with increased risk of relapse or recurrence, higher levels of impaired social and vocational function, and a worse long-term prognosis.8 A significant minority of patients having chronic TRD (20%–30%) do not have a satisfactory response to sequential trials of drug–drug and drug–psychotherapy combinations. Results from the STAR*D study demonstrated that ∼30% of patients did not achieve remission after 4 different vigorous and sequential antidepressant treatment trials.9

Chronic TRD is associated with persistent social and vocational disability, increased risk of suicide, greater medical morbidity and mortality, and higher health care utilization (HCU) and costs.10, 11, 12, 13, 14 Although depressive disorders are a leading cause of disability, morbidity, and mortality,15 they remain undertreated or untreated.16, 17

Several studies have examined the economic burden of TRD. These analyses have focused on patient populations characterized by depressions that are less chronic (ie, they have not responded to a minimum of 2 treatment trials). Published studies have not investigated the cost burden associated with more chronic and extensive forms of TRD characterized by nonresponse to ≥4 treatment trials.14, 18, 19, 20, 21 This distinction is clinically relevant when considering the potential use of various nonpharmacologic and nonpsychotherapy somatic treatments for TRD, which may be more costly and more invasive.

Electroconvulsive therapy (ECT), for example, has been shown to be highly effective for the treatment of TRD and is often considered an appropriate treatment option in these patients. However, for some patients, ECT may not be efficacious, well tolerated, or acceptable or it may be contraindicated.7, 22 Vagus nerve stimulation (VNS) was the first nonpharmacologic therapy approved by the US Food and Drug Administration for adjunctive treatment of chronic TRD characterized by inadequate response to ≥4 adequate antidepressant treatments, including ECT. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method for causing focal nonelectrical stimulation of the brain. In contrast to VNS, rTMS has been approved by the US Food and Drug Administration only for treatment of patients with depression who have not responded to a single antidepressant drug trial.23 Studies of rTMS have evaluated its use in MDD; however, its long-term efficacy, tolerability, and safety have not been well studied, and its effectiveness for more refractory forms of depression is not established.7 Other investigational somatic therapies for TRD include cortical brain stimulation22 and deep brain stimulation (DBS).24, 25 Similar to VNS, these therapies have been investigated in more chronically depressed patients who have not responded to at least 4 different types of antidepressant therapies.26, 27

The objective of the current study was to assess HCU and costs associated with chronic TRD, based on an inadequate response to ≥4 treatment trials (medication switches, augmentations, and combinations). Specifically, the key research objectives were to characterize HCU and cost for this TRD population, compare HCU and costs with those of individuals with non-TRD MDD, and to analyze the independent predictors of health care costs for a population with severe TRD. Quantifying and characterizing these economic factors is important for further investigating the cost-effectiveness of such therapies as ECT, TMS, VNS, cortical brain stimulation, and DBS for chronic TRD.

Section snippets

Study Population

This study included an analysis of administrative claims data from the PharMetrics Patient-Centric database over the period January 2001 through December 2009. This database combines medical and pharmacy claims from >95 different health plans across the United States and represents >17 million covered lives annually.28 We evaluated patients diagnosed with MDD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], 296.2x, 296.3x), dysthymic disorder

Results

A total of 83,112 individuals were identified as having MDD based on previously stated cohort inclusion criteria; 29.4% (24,415 patients) were classified as having TRD (Figure 1). Patient demographic characteristics are summarized in Table I. A greater proportion of TRD patients were female compared with non-TRD patients (73.6% vs 70.3%; P < 0.0001). TRD patients were observed to have longer periods of continuous enrollment than non-TRD patients (6.7 vs 6.5 years; P < 0.0001) and a longer

Discussion

This study demonstrates that the definition of TRD, based on adequate trials of 4 different antidepressant therapies, was associated with a significant increase in total medical expenditures when compared with MDD not meeting this definition of TRD. Patients classified with TRD have medical expenditures nearly 30% higher than non-TRD patients, when controlling for other factors. The burden associated with TRD highlights its importance to patients, physicians, and payers. These findings

Conclusions

TRD was associated with significantly higher HCU and medical expenditures compared with non-TRD MDD. The differences in annual health care expenditures per TRD patient were primarily driven by higher medical and pharmacy resource use. Furthermore, being classified as having TRD was associated with a clinically meaningful and statistically significant increase in total medical expenditures.

TRD is an area of ongoing research to develop understanding of factors that lead to resistance and the

Conflicts of Interest

Ms. Olchanski and Ms. Myers were employed by Boston Healthcare Associates but received no direct compensation from the sponsor. Ms. Halseth is an employee of Medtronic, Inc and has stock ownership in Medtronic. Mr. Cyr was employed by Boston Healthcare but received no direct compensation from the sponsor. Dr. Bockstedt is an employee of and has stock ownership in Medtronic. Dr. Goss is employed by Boston Healthcare but received no direct compensation from the sponsor. Dr. Howland has received

Acknowledgment

Research funding for this study was provided by Medtronic, Inc under contract to Boston Healthcare Associates. Ms. Olchanski participated in the design, analysis and interpretation of study results and provided review and comment during manuscript preparation. Ms. McInnis Myers participated in the design, analysis and interpretation of study results and development and review of the manuscript. Ms. Halseth participated in the design and interpretation of study results and provided review and

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