Economic Burden of Treatment-Resistant Depression on the U.S. Health Care System

J Manag Care Spec Pharm. 2019 Jul;25(7):823-835. doi: 10.18553/jmcp.2019.25.7.823.


Background: Treatment-resistant depression (TRD), defined as episodes of depression that do not respond to ≥ 2 lines of adequate depression therapy, is associated with a high economic burden. Although the economic burden of TRD is reported elsewhere, its exact magnitude and current value is uncertain due to differences in methodology in TRD identification.

Objective: To compare all-cause health care resource utilization (HCRU) and associated health care payments among patients with TRD and those with depression but without TRD, using administrative claims data.

Methods: This retrospective cohort study used data from the Truven Health MarketScan Commercial and Medicare Supplemental Databases (October 1, 2008-September 30, 2016). All patients were aged ≥ 18 years, newly diagnosed with depression (≥ 1 inpatient admission or ≥ 2 outpatient visits with a primary or secondary depression diagnosis), and newly treated with depression therapy. The population included patients with and without TRD. Patients with TRD were defined as having been treated with ≥ 3 courses of depression therapy within a 360-day period (initiation of the third course served as the TRD index date), while patients without TRD (non-TRD) were defined as having been treated with 2 courses of depression therapy. TRD and non-TRD cohorts were matched using propensity scores. Using the TRD index date of their matched TRD pair, non-TRD patients were assigned a simulated index date following second-line therapy. Eligible TRD and non-TRD patients were continuously enrolled from a 12-month baseline period before the first course of therapy through a 12-month follow-up period beginning with the TRD index date and simulated index date, respectively. Annual all-cause HCRU and associated payments (2016 U.S. dollars) were assessed in aggregate and by place of service during the follow-up period and were compared between the matched cohorts using nonparametric Wilcoxon signed-rank tests.

Results: The matched analysis included 800 patients in each cohort. For both cohorts, the mean age of patients was 39 years, and 60% were female. All clinical characteristics and all-cause HCRU were comparable at baseline. Compared with non-TRD patients, TRD patients had a significantly higher mean number of all-cause emergency department (ED) visits (0.29 vs. 0.24), outpatient visits (18.0 vs. 13.4), and prescriptions (30.0 vs. 24.0; all P < 0.05) during the 12-month follow-up period. The TRD cohort also had significantly higher mean total all-cause health care payments ($9,890 vs. $6,848; P < 0.001) and mean payments by place of service (ED: $518 vs. $408; outpatient: $3,603 vs. $2,585; pharmacy: $2,613 vs. $1,837; all P < 0.05) compared with the non-TRD cohort.

Conclusions: In relation to propensity score-matched non-TRD patients, TRD patients used significantly more resources (ED visits, outpatient visits, and number of prescriptions) and had significantly higher overall health care payments. These results serve to highlight the unmet need in patients with TRD, suggesting that improved and more effective management of these patients may help reduce the economic burden of disease.

Disclosures: This study was funded by Alkermes. Sussman and Menzin, employees of Boston Health Economics, were paid consultants, and Olfson, an employee of Columbia University Irving Medical Center, was an unpaid consultant to Alkermes in connection with the study and development of this research article. O'Sullivan and Shah are employees of the study sponsor. Results from this analysis were first presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting in Boston, MA, on April 23-26, 2018.

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / economics
  • Cohort Studies
  • Cost of Illness*
  • Delivery of Health Care / economics*
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Depressive Disorder, Treatment-Resistant / economics
  • Female
  • Health Care Costs / statistics & numerical data
  • Humans
  • Male
  • Medicare / economics
  • Middle Aged
  • Patient Acceptance of Health Care / statistics & numerical data
  • Retrospective Studies
  • United States
  • Young Adult


  • Antidepressive Agents