The DOI matches its Crossref record; 151 of the 155 references it cites were found in a registry or an index.
Treatment-resistant depression: therapeutic trends, challenges, and future directions
Open accessAbstract
BACKGROUND: Patients with major depression respond to antidepressant treatment, but 10%-30% of them do not improve or show a partial response coupled with functional impairment, poor quality of life, suicide ideation and attempts, self-injurious behavior, and a high relapse rate. The aim of this paper is to review the therapeutic options for treating resistant major depressive disorder, as well as evaluating further therapeutic options. METHODS: In addition to Google Scholar and Quertle searches, a PubMed search using key words was conducted, and relevant articles published in English peer-reviewed journals (1990-2011) were retrieved. Only those papers that directly addressed treatment options for treatment-resistant depression were retained for extensive review. RESULTS: Treatment-resistant depression, a complex clinical problem caused by multiple risk factors, is targeted by integrated therapeutic strategies, which include optimization of medications, a combination of antidepressants, switching of antidepressants, and augmentation with non-antidepressants, psychosocial and cultural therapies, and somatic therapies including electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, deep brain stimulation, transcranial direct current stimulation, and vagus nerve stimulation. As a corollary, more than a third of patients with treatment-resistant depression tend to achieve remission and the rest continue to suffer from residual symptoms. The latter group of patients needs further study to identify the most effective therapeutic modalities. Newer biomarker-based antidepressants and other drugs, together with non-drug strategies, are on the horizon to address further the multiple complex issues of treatment-resistant depression. CONCLUSION: Treatment-resistant depression continues to challenge mental health care providers, and further relevant research involving newer drugs is warranted to improve the quality of life of patients with the disorder.
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“A significant proportion of depressed people, ranging between one-half and two-thirds, do not reach a response threshold (Al-Harbi 2012; Trivedi 2006).”
From Psychotherapeutic treatments for depression in older adults (2024) · cites this paper as Al-Harbi 2012
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“It has been estimated that 10% to 30% of depression patients do not respond to antidepressant medication,32”
In the citing paper
“while more than a third fail to achieve remission even after several rounds of treatment ( Al-Harbi, 2012 , Gaynes et al., 2009 , Strawbridge et al., 2022 )”
From Self-blame-selective hyper-connectivity between anterior temporal and subgenual cortices predicts prognosis in major depressive disorder (2023) · cites this paper as Al-Harbi, 2012
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Cites
Sternbach, H. A. (1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.6.705 · Cited by 1,349
Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders
Sanacora, G., Zarate, C. A., Krystal, J. H., & Manji, H. K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2462 · Cited by 894
DEFINITION AND EPIDEMIOLOGY OF TREATMENT-RESISTANT DEPRESSION
Fava, M., & Davidson, K. G. (1996) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70283-5 · Cited by 797
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Brent, D. A., Emslie, G. J., Clarke, G. N., Wagner, K. D., Asarnow, J. R., Keller, M., Vitiello, B., Ritz, L., Iyengar, S., Abebe, K. Z., et al. (2008) · JAMA · doi:10.1001/jama.299.8.901 · Cited by 713
Tryptophan Hydroxylase-2 Controls Brain Serotonin Synthesis
Zhang, X., Beaulieu, J., Sotnikova, T. D., Gainetdinov, R. R., & Caron, M. G. (2004) · Science · doi:10.1126/science.1097540 · Cited by 683
Asarnow, J. R., Porta, G., Spirito, A., Emslie, G., Clarke, G., Wagner, K. D., Vitiello, B., Keller, M., Birmaher, B., McCracken, J., et al. (2011) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2011.04.003 · Cited by 632
Comorbid depression and anxiety spectrum disorders
Gorman, J. M. (1996) · Depression and Anxiety · doi:10.1002/(sici)1520-6394(1996)4:4 · Cited by 629
Sackeim, H. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00271-8 · Cited by 568
Research works printed but not linked: 4
- [5]American Psychiatric Association Practice Guideline for the Treatment of Patients with Major Depression 2000 Diagnostic and Statistical Manual of Mental Disorders 4th Edition Text Revision Washington, DC American Psychiatric Association 2000
- [37]Phillips KA Nierenberg AA The assessment and treatment of refractory depression J Clin Psychiatry 1994 55 20 26 8077165
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Cited by
Sorted by citations
Dendritic structural plasticity and neuropsychiatric disease
Forrest, M. P., Parnell, E., & Penzes, P. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.16 · Cited by 464
Treatment-resistant depression and peripheral C-reactive protein.
Chamberlain, S. R., Cavanagh, J., de Boer, P., Mondelli, V., Jones, D. N. C., Drevets, W. C., Cowen, P. J., Harrison, N. A., Pointon, L., Pariante, C. M., et al. (2019) · British Journal of Psychiatry · doi:10.1192/bjp.2018.66 · Cited by 400
“45,46 Because of the global burden of disability attributable to MDD, 47 the search for improved understanding of biomarkers of therapeutic resistance to current first-line treatment options is pressing.”
Neural basis of major depressive disorder: Beyond monoamine hypothesis
Boku, S., Nakagawa, S., Toda, H., & Hishimoto, A. (2018) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12604 · Cited by 402
Gut microbial metabolites in depression: understanding the biochemical mechanisms
Caspani, G., Kennedy, S. H., Foster, J. A., & Swann, J. R. (2019) · Microbial Cell · doi:10.15698/mic2019.10.693 · Cited by 289
Chahwan, B., Kwan, S., Isik, A., van Hemert, S., Burke, C., & Roberts, L. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.04.097 · Cited by 256
“Research indicates that these treatments are effective in reducing depressive symptoms, with approximately 60–70% of patients responding to treatment (Al-Harbi, 2012).”
Background
Metadata
- Authors
- Al-harbi
- Venue
- Patient Preference and Adherence
- Publisher
- Informa UK Limited
- Published
- 2012-05
- Volume
- 6
- Pages
- 369
- ISSN
- 1177-889X (ISSN-L)
- PMC
- PMC3363299
- OpenAlex
- W2016292245
- Cited by
- 796
- References
- 155
- Citations by year
- 2026: 75 · 2025: 76 · 2024: 104 · 2023: 95 · 2022: 107 · 2021: 91 · 2020: 63 · 2019: 56 · 2018: 38 · 2017: 33 · 2016: 18 · 2015: 15 · 2014: 14 · 2013: 6 · 2012: 3
- FWCI
- 8.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Patient Preference and Adherence (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- King Saud bin Abdulaziz University for Health Science
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- treatment-resistant depression, major depressive disorder, antidepressant augmentation, antidepressant switching, antidepressant combination therapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation, deep brain stimulation, vagus nerve stimulation, transcranial direct current stimulation, magnetic seizure therapy, psychosocial interventions, relapse
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