The DOI matches its Crossref record; 26 of the 27 references it cites were found in a registry or an index.
The Economic Burden of Treatment-Resistant Depression
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Mental illness can certainly be irremediable.27,28,29,30”
Citations
Cites
Kessler, R. C. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950010008002 · Cited by 12,370
Projections of Global Mortality and Burden of Disease from 2002 to 2030
Mathers, C. D., & Loncar, D. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030442 · Cited by 11,386
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., Rush, A. J., Walters, E. E., & Wang, P. S. (2003) · JAMA · doi:10.1001/jama.289.23.3095 · Cited by 7,988
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.11.1905 · Cited by 5,643
Diagnosis and definition of treatment-resistant depression
Fava, M. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00231-2 · Cited by 1,380
Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression
Lozano, A. M., Mayberg, H. S., Giacobbe, P., Hamani, C., Craddock, R. C., & Kennedy, S. H. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.05.034 · Cited by 1,024
Neuropsychopharmacology: The Fifth Generation of Progress
Sagduyu, K. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.7.1251-a · Cited by 1,023
Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression
Malone, D. A., Dougherty, D. D., Rezai, A. R., Carpenter, L. L., Friehs, G. M., Eskandar, E. N., Rauch, S. L., Rasmussen, S. A., Machado, A. G., Kubu, C. S., et al. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.08.029 · Cited by 897
Bewernick, B. H., Hurlemann, R., Matusch, A., Kayser, S., Grubert, C., Hadrysiewicz, B., Axmacher, N., Lemke, M., Cooper-Mahkorn, D., Cohen, M. X., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.013 · Cited by 865
Neuropsychopharmacology : The Fifth Generation of Progress
Davis, K. L., Charney, D. S., Coyle, J. T., & Nemeroff, C. B. (2002) · Lippincott Williams & Wilkins eBooks · Cited by 747
Flagged first, then by citations
1 of the 27 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Rush, 2005, Vagus nerve stimulation for treatment-resistant depression: a randomized controlled acute phase trial, Biol Psychiatry, 58, 347, 10.1016/j.biopsych.2005.05.025 · DOI · Paper page
Cited by
Sorted by citations
Items 101–145 of 145
Bienemann, B., Barbosa, A. R., da Cruz, L. V. M., Multedo, M., & Mograbi, D. C. (2023) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2023.2226414 · Cited by 5
“Between 20 and 30% of patients suffering from depression do not respond to treatment, leading to lower quality of life and higher medical costs (Olchanski et al. 2013).”
BackgroundWu, Z., Chen, L., Guo, Z., Li, K., Fu, Y., Zhu, J., Chen, X., Huang, C., Zheng, C., Ma, Y., et al. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.06.009 · Cited by 5
Wee, S. N., Liman, C., Waters, H. C., Houle, C. R., Rentería, M. E., Mukherjee, S. S., Surendran, S., Marcovici, J., Brubaker, M., Meehan, S. R., et al. (2023) · ClinicoEconomics and Outcomes Research · doi:10.2147/ceor.s395255 · Cited by 5
“Not achieving disease remission has been associated with a higher risk of relapse, impairment in social and work functioning, and a worse long-term prognosis.(7) In such cases, treatment may be augmented via adjunctive therapy.”
BackgroundInfluentialAkram, A., Al‐Sabahy, M., Al-Jedai, A. H., Almudaiheem, H., Farghally, M., Fallata, E. O., Alibrahim, O. A., Shoukry, T. M., Basu, S., Chalouhi, D., et al. (2022) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.1952 · Cited by 3
Trajectories of pharmacological therapies for treatment-resistant depression: a longitudinal study
DiBello, J. R., Xiong, X., Liu, X., Zhong, W., Merola, A., Li, M., & Lu, K. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-06518-8 · Cited by 4
Depression – ein komplexes dynamisches System
Schiepek, G. K. (2020) · Psychotherapie-Wissenschaft · doi:10.30820/1664-9583-2020-2-49 · Cited by 6
“20–30 % aller Patient*innen sprechen auf Standardbehandlungen nicht an und gelten als behandlungsresistent (Olchanski et al., 2013).”
BackgroundClunas, H., Walpole, S. J., Babic, I., Nair, M., May, N., Huang, X., Solowij, N., Newell, K. A., & Weston–Green, K. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111312 · Cited by 3
“…important in novel antidepressant research given that existing antidepressant medications have limited efficacy in 60 % of individuals (Otte et al., 2016; Turner et al., 2008) and 30 % of patients remain resistant to treatment despite polypharmacy (Olchanski et al., 2013; Zhdanava et al., 2021).”
Health Economics: The Hidden Costs of Mental Illness
Martini, D. R., & Attallah, T. (2019) · Springer eBooks · doi:10.1007/978-3-030-12665-0_1 · Cited by 3
Effect of Reliable Recovery on Health Care Costs and Productivity Losses in Emotional Disorders
Barrio‐Martínez, S., Ruiz‐Rodríguez, P., Medrano, L. A., Priede, A., Muñoz‐Navarro, R., Moriana, J. A., Carpallo-González, M., Prieto-Vila, M., Vindel, A. C., & González‐Blanch, C. (2023) · Behavior Therapy · doi:10.1016/j.beth.2023.08.012 · Cited by 3
Siyoum, M., Kibrom, E., Fanta, T., Matheyose, E., Adem, K., Dechasa, D. B., Asfaw, H., Darcho, S. D., & Dereje, J. (2024) · BMJ Open · doi:10.1136/bmjopen-2024-087006 · Cited by 4
Therapeutic Effect of Exercise on Mental Health
Parlakyıldız, S. (2024) · Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry · doi:10.18863/pgy.1458867 · Cited by 2
Impact of Depression and Mental Illness on Outcomes of Medical Illness in Older Adults
Boockvar, K. S. (2014) · Clinical Therapeutics · doi:10.1016/j.clinthera.2014.10.010 · Cited by 2
The economic burden of treatment-resistant depression: Cost-of-illness perspective
Niazi, S. K., & Bobo, W. V. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824067-0.00003-7 · Cited by 2
Ladha, K. S., Lee, J., Mattina, G. F., Pazmino‐Canizares, J., Wijeysundera, D. N., Nezhad, F. G., Tassone, V. K., Adamsahib, F., Lou, W. Y. W., Kennedy, S. H., et al. (2025) · BJPsych Open · doi:10.1192/bjo.2025.10823 · Cited by 2
The Efficacy of Transcranial Magnetic Stimulation for Major Depression: A Review of the Evidence
Janicak, P. G., & Carpenter, L. L. (2014) · Psychiatric Annals · doi:10.3928/00485713-20140609-06 · Cited by 2
Majör Depresif Bozuklukta Gen-Çevre Etkileşimi
Güngör, B. Ş., & Güngör, A. (2024) · Humanistic Perspective · doi:10.47793/hp.1350943 · Cited by 2
Söylemez, F., & Özer, A. (2018) · Sakarya Medical Journal · doi:10.31832/smj.429061 · Cited by 1
Neuromodulation Intervention in Resistant Depression
Prasetya, E. C., & Basoeki, L. (2020) · Jurnal Psikiatri Surabaya · doi:10.20473/jps.v8i2.17136 · Cited by 1
“229-234 [15] Olchanski N, McInnis Myers M, Halseth M, Cyr PL, Bockstedt L, Goss TF, et al.”
BackgroundSilverman, S. (2023) · Research Square · doi:10.21203/rs.3.rs-3253501/v1 · Cited by 1
Becker, T. M., & Lang, F. U. (2013) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12154
“uals involved, their families and carers, mental healthcare systems and society at large (3).”
BackgroundTrifirò, G., Sultana, J., Parrino, F., Tari, D. U., Fontana, A., Giorgianni, F., Ferrajolo, C., Troncone, C., Ientile, V., & Ap, C. (2016) · International Journal of Community & Family Medicine · doi:10.15344/2456-3498/2016/101
“The pharmaceutical cost of depression treatment is a relatively minor component of the overall costs [4-6].”
Tzalazidis, R. (2016) · Knowledge Commons (Lakehead University)
Monoamine Oxidase A in Relation to Subtypes and Treatment of Major Depressive Disorder
Chiuccariello, L. (2015) · TSpace (University of Toronto)
Lingford-Hughes, A. R., Watson, S., & Young, A. H. (2018) · The British Journal of Psychiatry · doi:10.1192/bjp.2018.266
Shah, D. (2019) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.3855
Experimental Models of Depression
Albayrak, İ. (2021) · Journal of Experimental and Basic Medical Sciences · doi:10.5606/jebms.2020.75626
“The main cause of the disease is thought to be a combination of genetic, environmental and physiological factors.[2,3]”
BackgroundVNTR Mutation in Monoamine Oxidase A in Depression and Anxiety: A Quantitative Survey
Yılancıoğlu, K., Kocabaş, A., Atasoy, S., Gocucu, K., & Pastirmaci, I. (2021) · Journal of Forensic Psychology
Boin, A. C. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2021.tde-04102021-164001
Tort, S., KODAN, E., Olğaç, S., Saar, S., Yıldız, A., ÜNAL, İ. S., Özdal, Z. D., & Tuğcu-Demiröz, F. (2022) · Sağlık Bilimlerinde Değer · doi:10.33631/sabd.1055227
SUBJECTIVE EXPERIENCES OF CLASSIC PSYCHEDELIC SUBSTANCES USERS
Bienemann, B. (2022) · doi:10.17771/pucrio.acad.59337 · Cited by 1
ÇELİK, A., Ener, D., & Çeti̇nkaya, F. (2022) · Eskişehir Türk Dünyası Uygulama ve Araştırma Merkezi Halk Sağlığı Dergisi · doi:10.35232/estudamhsd.1100784
Economic Evaluation of Mental Health Interventions
Jin, H., Jalali, A., Wijnen, B. F. M., & Bao, Y. (2023) · Frontiers research topics · doi:10.3389/978-2-8325-3692-6
Managing treatment resistant depression in primary care settings
Chauhan, M., Bogucki, O. E., Leasure, W. B., Sawchuk, C. N., Williams, M. D., & Katzelnick, D. J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824067-0.00036-0
Zhang, Q., Xiaowen, G., Li, W., Xiangqi, K., Haodong, W., Zheng, Y., Limin, Y., Jia, J., Mengmeng, S., Chaojuan, M., et al. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-07584-8
“Therefore, the development of targeted and efficacious TRD therapies is not only an urgent clinical priority but also of significant economic importance [20].”
Tang, J., Zheng, W., Ouyang, Y., Dong, J., & Qin, B. (2025) · Neurological Research · doi:10.1080/01616412.2025.2592116
Taipale, H. T., Reutfors, J., Tanskanen, A., Brandt, L., Tiihonen, J., DiBernardo, A., Mittendorfer-Rutz, E., & Brenner, P. (2020) · Figshare · doi:10.6084/m9.figshare.12299210
Jamieson, C., Popova, V., Daly, E., Cooper, K., Drevets, W. C., Rozjabek, H., & Singh, J. B. (2023) · Figshare · doi:10.6084/m9.figshare.22790569
Additional file 1 of Economic burden of major depressive disorder: a case study in Southern Iran
Keshavarz, K., Hedayati, A., Rezaei, M., Goudarzi, Z., Moghimi, E., Rezaee, M., & Lotfi, F. (2022) · Figshare · doi:10.6084/m9.figshare.20745390
Alhassan, M. A. (2026) · Annals of General Psychiatry · doi:10.1186/s12991-025-00626-1
“TRD imposes a significant economic burden across the GCC region, with overall expenditures, especially indirect costs, reported to be nearly three times greater than those linked to non-resistant MDD [9, 11].”
Online Psychological Counseling Based on Cognitive Behavioral Theraphy in Depression A Case Study
Korkmaz, K., & Çekiç, A. (2026) · Sinop Üniversitesi Sosyal Bilimler Dergisi · doi:10.30561/sinopusd.1835154
Paribello, P., Isayeva, U., Lazzardi, S., Pinna, M. A., Contu, M., Meloni, A., Pisanu, C., Squassina, A., Baune, B. T., & Manchia, M. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1819237
“TRD is associated with a 29.3% higher medical costs compared with patients with treatment responsive forms of MDD (Olchanski et al., 2013), and data from diverse patient populations such as Veterans (Szukis et al., 2021) or from outpatient settings (McCrone et al., 2018) converge in showing that…”
InfluentialRashidi, Y., Barjasteh, A. H., Ilaghi, M., Pozvei, A., Soltanpour, M., Jahangiri, S., Radmanesh, M., Pourbafrani, A., Faegh, S. H. H., Bagheri, F., et al. (2026) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2026.102741
“Major depressive disorder (MDD) is a debilitating condition marked by persistent depressed mood, reduced interest in activities, cognitive impairments, and vegetative symptoms, including disrupted appetite or sleep [148].”
Metadata
- Authors
- Olchanski, N., McInnis Myers, M., Halseth, M., Cyr, P. L., Bockstedt, L., Goss, T. F., & Howland, R. H.
- Affiliations
- Medtronic (United States) (US)
- University of Pittsburgh (US)
- Venue
- Clinical Therapeutics
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 35
- Issue
- 4
- Pages
- 512-522
- ISSN
- 0149-2918 (ISSN-L)
- OpenAlex
- W2064476618
- Cited by
- 146
- References
- 27
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 14 · 2022: 14 · 2021: 13 · 2020: 17 · 2019: 15 · 2018: 18 · 2017: 7 · 2016: 10 · 2015: 5 · 2014: 11 · 2013: 3
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medtronic
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › 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, chronic depression, economic burden, health care utilization, health care costs, direct medical costs
- MeSH terms
- Depression, Female, Humans, Male, Cost of Illness
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review