The Prevalence and National Burden of Treatment-Resistant Depression and Major Depressive Disorder in the United States
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OBJECTIVE: Estimates of prevalence and burden of treatment-resistant depression (TRD) vary widely in the literature. This study evaluated the prevalence and burden of TRD and the share of TRD in the burden of medication-treated major depressive disorder (MDD) using the most commonly accepted definition of TRD and a novel bottom-up approach. METHODS: Prevalence and health care burden of TRD were estimated by synthetizing inputs across 4 similarly designed claims studies in adults covered by Medicare, Medicaid, commercial plans, and the US Veterans Health Administration (VHA). Productivity (absenteeism and presenteeism) and unemployment burden were estimated based on inputs from a study conducted with data from the Kantar National Health and Wellness Survey (NHWS; 2017). A targeted literature search for additional inputs was performed. A cost model was developed to estimate the burden of TRD and medication-treated DSM-5-defined MDD in the United States. Study outcomes were the 12-month prevalence of TRD and the annual health care, productivity, and unemployment burden of TRD and medication-treated MDD in the United States. RESULTS: The estimated 12-month prevalence of medication-treated MDD in the United States was 8.9 million adults, and 2.8 million (30.9%) had TRD. The total annual burden of medication-treated MDD among the US population was $92.7 billion, with $43.8 billion (47.2%) attributable to TRD. The share of TRD was 56.6% ($25.8 billion) of the health care burden, 47.7% ($8.7 billion) of the unemployment burden, and 32.2% ($9.3 billion) of the productivity burden of medication-treated MDD. CONCLUSIONS: TRD is associated with disproportionate health care costs and unemployment, suggesting potentially large economic and societal gains with effective management.
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Persons of lower educational attainment or unemployed are more often resistant to multiple sequential antidepressant strategies.
“In ad di tion, persons of lower educational attain ment or unemployed are found to be more often resistant to multiple sequential antidepressant strategies 17,118 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [17]
The Unemployment Costs section (page not available) reports a higher incremental unemployment rate for adults with treatment-resistant depression than for those with non-resistant depression, supporting an association with unemployment. The paper defines resistance through successive antidepressant treatment courses, but the passages found do not establish that lower educational attainment is associated with resistance. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThere is a huge demand and supply gap for competent therapists considering that the estimated prevalence of treatment-resistant depression (TRD) in the U.S. is around 2.8 million people.
“there is a huge demand and supply gap for competent therapists considering that the estimated prevalence of treatment-resistant depression (TRD) in the U.S. is around 2.8 million people”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [258]
The Discussion reports an estimated 2.8 million US adults with treatment-resistant depression, supporting the prevalence figure. The cited passages do not establish a demand–supply gap for competent therapists, so that part of the sentence is unsupported by this source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSocioeconomic position is a risk factor for TRD in persons receiving monoamine-based antidepressants.
“Socioeconomic position is a risk factor for TRD in persons receiving monoamine- based antidepressants.”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [17]
The Discussion (page not provided) reports different TRD prevalence across insurance payer groups, but does not assess socioeconomic position as a risk factor. Searches for socioeconomic status, income, poverty, and monoamine-based antidepressants found no passage establishing the claimed relationship. (LLM, conf=0.72)
Experimental — accuracy not yet measuredApproximately one-third of patients with major depressive disorder do not achieve an antidepressant response despite treatment with multiple antidepressants and are considered to have treatment-resistant depression.
“Approximately one-third of patients with major depressive disorder (MDD) do not achieve an antidepressant response despite treatment with multiple antidepressants and are considered to have treatment-resistant depression (TRD) [1, 2].”
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- Authors
- Zhdanava, M., Pilon, D., Ghelerter, I., Chow, W., Joshi, K., Lefebvre, P., & Sheehan, J. J.
- Affiliations
- Analysis Group (United States) (US)
- Janssen Scientific Affairs (United States) (US)
- Corresponding author
- Zhdanava, Maryia
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2021-03-16
- Volume
- 82
- Issue
- 2
- ISSN
- 0160-6689 (ISSN-L)
- 1555-2101
- OpenAlex
- W3146268156
- Cited by
- 523
- References
- 20
- Citations by year
- 2026: 110 · 2025: 124 · 2024: 136 · 2023: 108 · 2022: 36 · 2021: 8 · 2012: 1
- FWCI
- 42.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Janssen Scientific Affairs
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Health Systems, Economic Evaluations, Quality of Life
- Keywords
- treatment-resistant depression, major depressive disorder, prevalence, economic burden, health care costs, productivity loss, absenteeism, presenteeism, unemployment, cost model, bottom-up approach, claims data
- MeSH terms
- Absenteeism, Adult, Antidepressive Agents, Major Depressive Disorder, Humans, United States, Prevalence, Health Care Costs, Cost of Illness, Depressive Disorder, Treatment-Resistant
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