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A Review of the Clinical, Economic, and Societal Burden of Treatment-Resistant Depression: 1996–2013
David A. Mrazek, M.D.; John C. Hornberger, M.D., M.S.; C. Anthony Altar, Ph.D.; Irina Degtiar, B.A., B.S.
Psychiatric Services 2014; doi: 10.1176/appi.ps.201300059
View Author and Article Information

At the time of this research, Dr. Mrazek, who is deceased, was with the Mayo Clinic, Rochester, Minnesota. Dr. Hornberger and Ms. Degtiar are with Cedar Associates, L.L.C., Menlo Park, California. Dr. Hornberger is also with the Department of Internal Medicine, Stanford University School of Medicine, Stanford, California. Dr. Altar is with Assurex Health, Mason, Ohio. Send correspondence to Dr. Hornberger (e-mail: jhornberger@cedarecon.com).

Copyright © 2014 by the American Psychiatric Association

Abstract

Objective  This literature review assessed the burden of treatment-resistant depression in the United States by compiling published data about the clinical, societal, and economic outcomes associated with failure to respond to one or more adequate trials of drug therapy.

Methods  PubMed and the Tufts Cost-Effectiveness Analyses Registry were searched for English-language articles published between January 1996 and August 2013 that collected primary data about treatment-resistant depression. Two researchers independently assessed study quality and extracted data.

Results  Sixty-two articles were included (N=59,462 patients). Patients with treatment-resistant depression had 3.8±2.1 prior depressive episodes and illness duration of 4.4±3.3 years and had completed 4.7±2.7 unsuccessful drug trials involving 2.1±.3 drug classes. Response rates for treatment-resistant depression were 36%±1%. A total of 17%±6% of patients had prior suicide attempts (1.1±.2 attempts per patient). Quality-of-life scores (scale of 0–1, with 0 indicating death and 1 indicating perfect health) for patients with treatment-resistant depression were .41±.8 and .26±.8 points lower, respectively, than for patients who experienced remission or response. Annual costs for health care and lost productivity were $5,481 and $4,048 higher, respectively, for patients with treatment-resistant versus treatment-responsive depression.

Conclusions  Treatment-resistant depression exacts a substantial toll on patients’ quality of life. At current rates of 12%–20% among all depressed patients, treatment-resistant depression may present an annual added societal cost of $29–$48 billion, pushing up the total societal costs of major depression by as much as $106–$118 billion. These findings underscore the need for research on the mechanisms of depression, new therapeutic targets, existing and new treatment combinations, and tests to improve the efficacy of and adherence to treatments for treatment-resistant depression.

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Table 1Baseline characteristics of patients enrolled in studies of treatment-resistant depressiona
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a SDs and minimum and maximum percentages are not reported when only one study provided results.

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b The following list reports percentages of patients with treatment-resistant vs. treatment-responsive depression and other conditions: mixed personality disorder, 14% vs. data not reported (DNR); borderline personality disorder, 13% vs. 13%; paranoid personality disorder, 13% vs. 28%; migraine, 12% vs. 9%; social phobia, 12% vs. 35%; dependent personality disorder, 11% vs. 15%; simple phobia, 11% vs. 14%; generalized anxiety disorder, 10% vs. 16%; agoraphobia, 10% vs. 7%; passive-aggressive personality disorder, 9% vs. 13%; physical abuse, 9% vs. DNR; posttraumatic stress disorder, 9% vs. 4%; soft tissue disorder, 7% vs. 0%; somatoform disorder, 5% vs. 5%; antisocial personality disorder, 5% vs. 7%; eating disorder, 5% vs. 3%; narcissistic personality disorder, 4% vs. 10%; obsessive-compulsive disorder, 4% vs. 3%; acute myocardial infarction persistent, 3% vs. DNR; mood disorders, 3% vs. 1%; dysthymia, 3% vs. DNR; dementia, 2% vs. 2%; gastritis and duodenitis, 2% vs. 4%; schizoid personality disorder, 2% vs. 3%; phobic anxiety disorders, 2% vs. 3%; mild mental retardation, 1% vs. 2%; and histrionic personality disorder, 0% vs. 3%

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Table 2Baseline measures of symptom severity among patients with treatment-resistant depressiona
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a SDs and minimum and maximum scores are not reported when only one study provided results. HAM-D, Hamilton Rating Scale for Depression; MADRS, Montgomery-Asberg Depression Scale; CGI-S, Clinical Global Impression–Severity; BDI, Beck Depression Inventory; IDS, Inventory of Depressive Symptomatology; SR, Self-Report; C, Clinician Rated; QIDS, Quick Inventory of Depressive Symptomatology; GAF, Global Assessment of Functioning; BPRS, Brief Psychiatric Rating Scale; Q-LES-Q, Quality of Life Enjoyment and Satisfaction Questionnaire; BAI, Beck Anxiety Inventory; HAMA, Hamilton Anxiety Scale; MMSE, Mini-Mental State Examination; SF-36, Short-Form Health Survey Questionnaire; MCS, mental composite score; PCS, physical composite score; SQ, Symptom Questionnaire; SS, somatic subscale; SWB, somatic well-being; POMS, Profile of Mood States.

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b Excluded studies that reported the number of failed drug trials and classes as ranges.

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Table 3Rates of response and remission among patients with treatment-resistant depression, by studya
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a For studies that assessed only one treatment, the treatment is listed under lowest response or remission rate, and results are listed under average response or remission rates.

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b HAM-D, Hamilton Rating Scale for Depression; MADRS, Montgomery-Asberg Depression Scale; QIDS-SR, Quick Inventory of Depressive Symptomatology–Self-Report

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c Weighted by inverse-variance method. Excludes patients on placebo

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Table 4Costs per patient-year for patients with treatment-resistant and treatment-responsive depression, by resource categorya
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a Costs are for private payers and are reported in 2012 dollars.

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b An SD and other data were not reported when only one study provided results.

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c May include other costs that are not listed

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The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 26.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 26.  >
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