Treatment-Resistant Depression: Approaches to Treatment
Abstract
Approximately 30% of people treated for a major depressive episode will not achieve remission after two or more treatment trials of first-line antidepressants and are considered to have treatment-resistant depression (TRD). Because the odds of remission decrease with every subsequent medication trial, it is important for clinicians to understand the characteristics and risk factors for TRD, subtypes of major depressive disorder that are more likely to be less responsive to first-line anti-depressants, and the available treatment options. In the current article, we review the approved treatments for TRD, including esketamine, and the evidence for psilocybin and pramipexole. Although limited in specificity, guidelines to help prescribers identify person-centered treatments for TRD are available. [ Journal of Psychosocial Nursing and Mental Health Services, 59 (9), 7–11.]
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Many patients will require multiple medication trials and may take months to experience any symptomatic improvement.
“Furthermore, many patients will require multiple medication trials and may take months to experience any symptomatic improvement [36].”
Cites
Vos, T., Lim, S. S., Abbafati, C., Abbas, K. M., Abbasi, M., Abbasifard, M., Abbasi-Kangevari, M., Abbastabar, H., Abd-Allah, F., Abdelalim, A., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30925-9 · Cited by 19,358 · see citing works
Epidemiology of Adult <i>DSM-5</i> Major Depressive Disorder and Its Specifiers in the United States
Hasin, D. S., Sarvet, A. L., Meyers, J. L., Saha, T. D., Ruan, W. J., Stohl, M., & Grant, B. F. (2018) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.4602 · Cited by 1,737 · see citing works
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial
Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.3285 · Cited by 1,301 · see citing works
A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders
Sanacora, G., Frye, M. A., McDonald, W., Mathew, S. J., Turner, M. S., Schatzberg, A. F., Summergrad, P., Nemeroff, C. B., & for the American Psychiatric Association (APA) Council of Research Task Force on Novel Biomarkers and Treatments (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.0080 · Cited by 576 · see citing works
Defining treatment‐resistant depression
Gaynes, B. N., Lux, L., Gartlehner, G., Asher, G., Forman‐Hoffman, V., Green, J., Boland, E., Weber, R. P., Randolph, C., Bann, C., et al. (2020) · Depression and Anxiety · doi:10.1002/da.22968 · Cited by 447 · see citing works
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Inserra, A., De Gregorio, D., & Gobbi, G. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000056 · Cited by 232 · see citing works
A New Prediction Model for Evaluating Treatment-Resistant Depression
Kautzky, A., Baldinger-Melich, P., Kranz, G. S., Vanicek, T., Souery, D., Montgomery, S., Mendlewicz, J., Zohar, J., Serretti, A., Lanzenberger, R., et al. (2017) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.15m10381 · Cited by 94 · see citing works
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Selected biomarkers of depression: what are the effects of cytokines and inflammation
Harsanyi, S., Kupcova, I., Danisovic, L., & Klein, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010578 · Cited by 299 · see citing works
“New treatment targets, be they psychological or pharmaceutic, are constantly being developed, as depression can often be therapy-resistant [12,13].”
BackgroundAccelerated intermittent theta burst stimulation in major depressive disorder: A systematic review.
Neuteboom, D., Zantvoord, J., Goya-Maldonado, R., Wilkening, J., Dols, A., van Exel, E. V., Lok, A., de Haan, L., & Scheepstra, K. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115429 · Cited by 54 · see citing works
Shen, C., Wang, K., Wang, H., Gao, Y., Nie, K., Jiang, X., Su, H., Tang, Y., Lu, F., Dong, H., et al. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107090 · Cited by 37 · see citing works
Psiuk, D., Nowak, E., Dycha, N., Łopuszańska, U., Kurzepa, J., & Samardakiewicz, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911450 · Cited by 34 · see citing works
“TRD affects approximately 30 percent of people treated for a major depressive episode and is associated with increased severity and recurrence of disease, which results in prolonged function impairments, medical comorbidities, and increased suicidality as well as non-suicidal mortality [7,8].”
BackgroundLan, X.-J., Yang, X.-H., Mo, Y., Deng, C.-J., Huang, X.-B., Cai, D.-B., & Zheng, W. (2024) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2024.104032 · Cited by 32 · see citing works
Han, D., Zhao, Z., Mao, T., Gao, M., Yang, X., & Gao, Y. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70150 · Cited by 30 · see citing works
“Recently, rapid progress has been made in the study of depression pathogenesis and the identification of specific drug treatment targets [134].”
Potential Therapeutic Effects of Psilocybin: A Systematic Review
Goel, D. B., & Zilate, S. (2022) · Cureus · doi:10.7759/cureus.30214 · Cited by 30 · see citing works
“For STAI-estimated uneasiness side effects, a similar outcome was observed [18-20].”
ResultKato, M., Nakagome, K., Baba, T., Sonoyama, T., Okutsu, D., Yamanaka, H., Shimizu, R., Motomiya, T., & Inoue, T. (2023) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13569 · Cited by 27 · see citing works
“The odds of remission decrease with every subsequent line of treatment.(5) Additionally, the time to response to existing antidepressants is usually long (weeks to months), thereby necessitating long-term treatment to achieve remission.”
BackgroundP300 parameters in major depressive disorder: A systematic review and meta-analysis
Arıkan, M., Ilhan, R., Orhan, Ö., Esmeray, M. T., Turan, Ş., Gica, Ş., Bakay, H., Pogarell, O., Tarhan, K., & Metin, B. (2024) · World Journal of Biological Psychiatry · doi:10.1080/15622975.2024.2321554 · Cited by 24 · see citing works
“The rate of treatment-resistant depression is approximately 30% (Kverno and Mangano 2021).”
BackgroundSocała, K., Żmudzka, E., Lustyk, K., Zagaja, M., Brighenti, V., Costa, A., Andres-Mach, M., Pytka, K., Martinelli, I., Mandrioli, J., et al. (2024) · Phytotherapy Research · doi:10.1002/ptr.8101 · Cited by 24 · see citing works
Wong, S., Kwan, A. T. H., Teopiz, K., Le, G.-H., Meshkat, S., Ho, R. C. M., d'Andrea, G., Cao, B., Vincenzo, J. D. D., Rosenblat, J., et al. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.01.142 · Cited by 24 · see citing works
Lin, Y.-W., Tu, Y.-K., Hung, K.-C., Liang, C.-S., Tseng, P.-T., Lin, P., Lai, E. C.-C., & Hsu, C.-W. (2023) · EClinicalMedicine · doi:10.1016/j.eclinm.2023.102308 · Cited by 23 · see citing works
Ketamine and the Disinhibition Hypothesis: Neurotrophic Factor-Mediated Treatment of Depression
Borsellino, P., Krider, R. I., Chea, D., Grinnell, R., & Vida, T. A. (2023) · Pharmaceuticals · doi:10.3390/ph16050742 · Cited by 22 · see citing works
“With the rising prevalence of MDD in the US, treatment-resistant depression (TRD) is also occurring at an increased rate [15].”
BackgroundHMGB1 in depression: An overview of microglial HMBG1 in the pathogenesis of depression
Huang, X., Wang, B., Yang, J., Lian, Y.-J., Yu, H., & Wang, Y.-X. (2023) · Brain, Behavior, & Immunity - Health · doi:10.1016/j.bbih.2023.100641 · Cited by 22 · see citing works
Li, Z.-J., Wu, Q.-X., Peng, P., Wu, M., Liu, S.-H., & Liu, T.-Q. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115640 · Cited by 21 · see citing works
Wang, Q., Huang, H., Li, D., Wang, Y.-T., Qi, N., Ci, Y., & Xu, T.-C. (2022) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2022.103189 · Cited by 20 · see citing works
Roberts, B., Cooper, Z., Lu, S., Stanley, S., Majda, B. T., Collins, K. R., Gilkes, L., Rodger, J., Akkari, P., & Hood, S. D. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1267294 · Cited by 19 · see citing works
“Furthermore, this same third of people treated for depression who do not show full remission following two or more treatment trials of first-line antidepressants may develop a persistent depressive disorder (Kverno and Mangano, 2021).”
BackgroundA focus on Rho/ROCK signaling pathway: An emerging therapeutic target in depression.
Hanifa, M., Singh, M., Randhawa, P., Jaggi, A., & Bali, A. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175648 · Cited by 18 · see citing works
Yuan, M., & Yuan, B. (2022) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2022.102157 · Cited by 18 · see citing works
Sun, J.-F., Luo, Y., Ma, Y., Guo, C.-L., Du, Z., Gao, S.-S., Chen, L.-M., Wang, Z., Li, X., Xu, K., et al. (2022) · Brain Science · doi:10.3390/brainsci12121604 · Cited by 17 · see citing works
“Major depressive disorder (MDD) is the most common psychiatric disorder, and even though MDD receives standardized treatment, 30% of MDD patients are still clinically ineffective or have poor outcomes [1].”
BackgroundImans, D., Abuhmed, T., Alharbi, M., & El–Sappagh, S. (2024) · Diagnostics · doi:10.3390/diagnostics14212385 · Cited by 15 · see citing works
Genetic modulation of the HTR2A gene reduces anxiety-related behavior in mice
Rohn, T., Radin, D., Brandmeyer, T., Linder, B. J., Andriambeloson, E., Wagner, S., Kehler, J., Vasileva, A., Wang, H.-E., Mee, J. L., et al. (2023) · PNAS Nexus · doi:10.1093/pnasnexus/pgad170 · Cited by 16 · see citing works
“Noninvasive CNS delivery of CRISPR/Cas9 may have important implications for the next generation of psychotropic medications, particularly for patients exhibiting treatment-resistant anxiety or depression (13, 14).”
BackgroundTseng, V. W. S., Tharp, J. A., Reiter, J. E., Ferrer, W., Hong, D., Doraiswamy, P. M., & Nickels, S. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115702 · Cited by 15 · see citing works
“…remains difficult to effectively treat, with approximately 30% of people treated for a major depressive episode not achieving remission after two or more treatment trials of first-line antidepressants (e.g., selective serotonin reuptake inhibitors; Gaynes et al., 2009; Kverno et al., 2021).”
Pathak, P., Mehra, A., Ram, S., Pal, A., & Grover, S. (2022) · Behavioural Brain Research · doi:10.1016/j.bbr.2022.113931 · Cited by 15 · see citing works
Zhu, Y., Wu, T., Jiao, Q., Chai, H.-T., Wang, Y., Tian, C.-X., Xue, Q., Li, K., Wang, P., Li, Z.-B., et al. (2025) · Science Advances · doi:10.1126/sciadv.adx2666 · Cited by 13 · see citing works
“Our findings indicate that the application of REM SD with pharmacological treatments could help address the therapeutic challenges related to the high incidence of depression and treatment-resistant depression in women within clinical settings ( 65, 66 ).”
SARM1 Deficiency Induced Depressive-like Behavior via AMPKα/p-eEF2 axis to Synapse Dysfunction.
Li, W.-F., Zhu, W., Chen, J.-H., Ali, T., & Li, S.-P. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110206 · Cited by 13 · see citing works
The prevalence and economic burden of treatment-resistant depression in Thailand
Prasartpornsirichoke, J., Pityaratstian, N., Poolvoralaks, C., Sirinimnualkul, N., Ormtavesub, T., Hiranwattana, N., Phonsit, S., & Rungnirundorn, T. (2023) · BMC Public Health · doi:10.1186/s12889-023-16477-y · Cited by 13 · see citing works
“This finding is consistent with prior international investigations, which have indicated a considerable variation in TRD prevalence, ranging from 12 to 55% [30].”
ResultZhu, H., Zhang, Y., Duan, Y., Pei, K., Tu, S., Chen, Y., & Cai, H. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.116817 · Cited by 13 · see citing works
Barreiros, A. R., Breukelaar, I., Prentice, A., Mayur, P., Tomimatsu, Y., Funayama, K., Foster, S., Malhi, G., Arns, M., Harris, A., et al. (2024) · NeuroImage: Clinical · doi:10.1016/j.nicl.2024.103656 · Cited by 12 · see citing works
“Although several therapeutic interventions are accessible for its management, attaining remission has proven challenging (Kverno and Mangano, 2021).”
BackgroundWang, T., Dai, L., Lai, Y.-J., Wang, F.-T., Zhang, Y.-Y., Wang, Y.-H., Li, D.-Y., Zhan, S.-K., Bian, L.-G., & Sun, B.-M. (2024) · Journal of Neurosurgery · doi:10.3171/2023.10.jns231855 · Cited by 12 · see citing works
Ma, Y., Zhou, X., Zhang, F., Huang, C., Yang, H., Chen, W.-S., & Tao, X. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1313871 · Cited by 11 · see citing works
Wan, X.-J., Xie, J.-L., Yang, M.-J., Yu, H., Hou, W.-K., Xu, K., Wang, J.-C., & Xu, P. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12041405 · Cited by 11 · see citing works
“The treatment of depression mainly involves psychological counseling and medication, but the results are often unsatisfactory [9].”
BackgroundPredictors of response to accelerated rTMS in the treatment of treatment-resistant depression
Wang, Q., Li, L., Zhao, H., Cheng, W., Cui, G., Fan, L., Dong, X.-M., Xu, T.-C., & Geng, Z.-L. (2024) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-024-01903-y · Cited by 10 · see citing works
“Approximately 30% of patients with MDD do not experience a sufficient response to initial anti - depressant treatments and may develop treatment-resistant depression (TRD) [1].”
Zhang, M., Wei, X., Li, S.-Y., Liu, Q.-M., Huang, X., Huang, X.-B., Yang, X.-H., & Zheng, W. (2024) · ALPHA PSYCHIATRY · doi:10.5152/alphapsychiatry.2024.231402 · Cited by 10 · see citing works
“While one study found that electroconvulsive therapy (ECT) for MDD yielded equally effective outcomes in both sexes, 20 another study identified interleukin-6 as a significant predictor of antidepressant effects for females but not males with TRD. 16 Nonconvulsive electrotherapy (NET), a novel…”
ResultBrandão, A. A. C., Deus, D. L. S., Duarte-Filho, L. A., Menezes, P., Massaranduba, A. B. R., Silva, F., & Ribeiro, L. A. A. (2023) · Pharmacology, Biochemistry and Behavior · doi:10.1016/j.pbb.2023.173674 · Cited by 10 · see citing works
D'aprile, I., Petrillo, G., Zonca, V., Mazzelli, M., Cillis, F. D., Benedetto, M. D. D., Riva, M. A., & Cattaneo, A. (2025) · Progress in Neuro-psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111344 · Cited by 9 · see citing works
Cold water swimming as an add-on treatment for depression: a feasibility study
Hjorth, P., Sikjaer, M., Løkke, A., Jørgensen, A., Jørgensen, N., Kaasgaard, D. M., & Rasmussen, M. (2023) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2023.2228290 · Cited by 9 · see citing works
“Effective treatment with no or few side effects is needed for patients with depression and new treatments based on patient preferences are warranted [6].”
BackgroundSinganwad, P., Tatode, A. A., Qutub, M., Taksande, B., Umekar, M., Trivedi, R., & Premchandani, T. (2025) · Neuropeptides · doi:10.1016/j.npep.2025.102538 · Cited by 8 · see citing works
Oxytocin in the Treatment of Psychiatric Disorders
Kagizman, S. C., & Hocaoğlu, Ç. (2023) · Medeniyet Medical Journal · doi:10.4274/mmj.galenos.2023.13707 · Cited by 8 · see citing works
Electroconvulsive Therapy for Treatment-Resistant Depression: Dispelling the Stigma.
Salani, D. A., Goldin, D., Valdes, B., & DeSantis, J. (2023) · Journal of Psychosocial Nursing and Mental Health Services · doi:10.3928/02793695-20230222-02 · Cited by 8 · see citing works
Exploring Biological Risk Factors in Treatment-Resistant Depression
Liévanos-Ruiz, F. J., & Fenton-Navarro, B. (2025) · Psychiatry International · doi:10.3390/psychiatryint6040134 · Cited by 7 · see citing works
“Due to the interconnection of neurotransmitter systems, an imbalance in one can affect others, leading to a global disruption that hinders recovery [4,8].”
Jóźwiak-Bębenista, M., Wiktorowska-Owczarek, A., Siatkowska, M., Komorowski, P., Włodarczyk, A., Kowalczyk, E., & Sokołowska, P. (2025) · Cells · doi:10.3390/cells14110831 · Cited by 7 · see citing works
“Until recently, advances in antidepressant therapy had limited success in treating individuals with TRD [18,19].”
Olivier, N., Harvey, B. H., Gobec, S., Shahid, M., Košak, U., Žakelj, S., & Brink, C. (2025) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2025.118093 · Cited by 7 · see citing works
Impact of the gut microbiota-Th17 cell axis on inflammatory depression
Jia, X., Wang, J., Ren, D., Zhang, K.-B., Zhang, H., Jin, T., & Wu, S. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1509191 · Cited by 7 · see citing works
Kavakbasi, E., van Assche, E., Schwarte, K., Hohoff, C., & Baune, B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084196 · Cited by 7 · see citing works
“About one third of patients with depression do not adequately respond to antidepressant pharmacotherapy [3].”
BackgroundOliveira-Maia, A., Rive, B., Morrens, J., Godinov, Y., Cabrieto, J., Perualila, N., & Mulhern-Haughey, S. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1250987 · Cited by 7 · see citing works
“It is widely acknowledged that TRD is a difficult condition to treat (6, 11, 13, 31).”
BackgroundXu, Y., Chen, D.-Y., Ye, Q., Zhang, P., Shi, J., Li, S., Sun, Y., Zhao, Z., Tang, Y.-X., Zhang, P., et al. (2026) · MedComm · doi:10.1002/mco2.70739 · Cited by 6 · see citing works
“Similarly, a significant proportion of patients with drug-resistant epilepsy (DRE) or treatment-resistant depression fail to achieve adequate symptom control with existing therapies [ 10, 11 ].”
Ma, L., Chen, S., Zhang, Y., Qin, X., & Wu, X. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.10.002 · Cited by 6 · see citing works
“Current treatments for depressive disorder are mainly based on long-term oral selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, and psychotherapy (Kverno and Mangano, 2021).”
BackgroundYang, R.-C., Li, Z., Zhu, Y.-Z., Wu, Y., Lu, X., Zhao, X., Liu, J.-J., Du, X.-D., & Zhang, X.-Y. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-05860-7 · Cited by 6 · see citing works
Porras-Segovia, A., Escobedo-Aedo, P., de Albornoz, C. M. C., Guerrero-Jiménez, M., Lis, L., Molina-Madueño, R., Gutiérrez-Rojas, L., & Alacreu-Crespo, A. (2024) · Current Psychiatry Reports · doi:10.1007/s11920-024-01511-6 · Cited by 6 · see citing works
“Therefore, it is estimated that approximately 30% of patients do not respond to conventional treatment with traditional psycho-therapies and antidepressants [8], so therapeutic strategies need to be enhanced to improve this scenario.”
Li, X.-T., Tian, Y.-S., Phillips, M., Xiao, S.-Y., Zhang, X., Li, Z.-C., Liu, J., Li, L.-J., Zhou, J.-S., & Wang, X.-P. (2023) · BMC Public Health · doi:10.1186/s12889-023-16542-6 · Cited by 6 · see citing works
“Depression is a recurring disorder that is often treat-ment-resistant; 20 ~ 40% of patients treated for a major depressive disorder do not achieve remission after two or more courses of treatment with different antidepressants [4, 5].”
BackgroundThe Role of Psychotherapy in the Management of Treatment-Resistant Depression.
Rogan, T., & Wilkinson, S. T. (2023) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2023.02.006 · Cited by 6 · see citing works
Ye, K., Cao, Y., Wu, Y.-H., Ning, C., Wang, D.-W., Guo, H., Wang, Y.-H., Zhang, Y.-Y., Qiu, X., Li, N., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03669-w · Cited by 5 · see citing works
“Despite receiving adequate antidepressant treatments, approximately 30% of patients exhibit treatment-resistant depression (TRD), wherein clinical symptoms remain refractory to conventional interventions [2].”
Zhu, W., Chang, J.-L., Tian, L., Yang, X., & Li, W.-F. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70394 · Cited by 5 · see citing works
“Despite extensive research, significant gaps remain in understanding its etiology and underlying molecular mechanisms, hindering the development of rapid and effective treatments [5].”
Winczewska, Z., Mechlińska, A., Radziwiłłowicz, P., Konieczna, L., Drżeżdzon, J., Jacewicz, D., Wiglusz, M., Bączek, T., Cubała, W., & Górska-Ponikowska, M. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103547 · Cited by 5 · see citing works
“TRD affects up to 30 % of people treated for a major depressive episode, in whom therapeutic success is not achieved after two or more attempts at antidepressant drug therapy [45].”
Sadeghzadeh, S., Swaminathan, A., Bhanot, P., Steeman, S., Xu, A., Shah, V., Purger, D., & Buch, V. P. (2024) · Biological Psychiatry: Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2024.04.007 · Cited by 5 · see citing works
Wei, L., Qi, X.-Y., Yu, X.-L., Zheng, Y., Luo, X.-R., Wei, Y., Ni, P.-Y., Zhao, L.-S., Wang, Q., Ma, X.-H., et al. (2023) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2023.115252 · Cited by 5 · see citing works
Multi-omics analysis reveals the mechanism of action of Atractylodin against depression
Bao, S., Feng, M., Zhang, X.-Z., Xie, M., & Teng, J. (2025) · Journal of Natural Medicines · doi:10.1007/s11418-025-01930-6 · Cited by 4 · see citing works
“Currently, antidepressant medications and psychotherapy are the main treatment strategies, but some patients still do not respond well to existing therapies, exhibiting treatment resistance [39].”
Quantitative evaluation of multiple treatment regimens for treatment-resistant depression
Feng, Y., Lv, Y.-H., Yang, J., Xu, L., Chen, J.-C., Huang, J.-H., Ren, J.-Y., Zheng, Q., & Li, L.-J. (2025) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaf007 · Cited by 4 · see citing works
“29 Quetiapine, another atypical antipsychotic, blocks dopamine D2 and serotonin 5-HT2 receptors and has affinity for other serotonin, norepinephrine, and histamine receptors, which can alleviate depressive symptoms and is used in the treatment of TRD. 30 This study shows that the efficacy of quetiapine combined with S…”
InfluentialThe Effect of Probiotic Lactic Acid Bacteria on the Symptoms of Mental Disorders
Novikova, V., Bondarenko, K., Sazonov, A., & Rozanov, A. S. (2024) · Nanobiotechnology Reports · doi:10.1134/s2635167624602092 · Cited by 4 · see citing works
Li, Y., Yin, Y., Yu, Y., Hu, X.-W., Liu, X., & Wu, S. (2024) · Early Intervention in Psychiatry · doi:10.1111/eip.13509 · Cited by 4 · see citing works
“…vary (Belmaker & Agam, 2008), more than half of MDD may still experience a relapse of depressive symptoms 3 – 12 months after initial drug treatment (Kverno & Mangano, 2021; Wang et al., 2022), and some patients may undergo multiple episodes of depression years after their initial treatment,…”
Głombik, K., Kukla-Bartoszek, M., Curzytek, K., Basta-Kaim, A., & Budziszewska, B. (2024) · Pharmacological Reports · doi:10.1007/s43440-023-00559-0 · Cited by 4 · see citing works
“Options for depression treat-ment are limited, and patients are dealing with poor or unsat-isfactory drug responses [15].”
BackgroundYin, X., Chen, S., Ju, X., & Hu, X.-W. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1170890 · Cited by 4 · see citing works
Unraveling the Mysteries of Mental Illness With Psilocybin
Sottile, R., Singh, H., Weisman, A., & Vida, T. A. (2022) · Cureus · doi:10.7759/cureus.25414 · Cited by 4 · see citing works
“These phenomena have led to a new diagnosable condition, treatment-resistant depression, which occurs in 30% of patients treated for major depressive disorder, and is defined as a failure to achieve disease remission after treatment with at least two first-line antidepressants [35].”
BackgroundZeng, D., Zheng, Y., Zhao, X.-X., Li, S., Luo, L., Xie, W.-J., Zhang, P., Li, G.-J., He, S., Yu, Y.-M., et al. (2026) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2026.106515 · Cited by 3 · see citing works
Horato, N., Dalvi-Garcia, F., Dutra, P. H. P., & Nardi, A. (2026) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000002122 · Cited by 3 · see citing works
Psilocybin-assisted psychotherapy in adults with depression - A literature review.
Dorczok, M. C., Mittmann, G., Ettl, T., & Steiner-Hofbauer, V. (2025) · Progress in Neuro-psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111508 · Cited by 3 · see citing works
Tang, X., Wang, C.-C., Huang, Q.-W., Yang, C., Lan, S.-J., Yen, Y., & Yu, C.-C. (2025) · Scientific Reports · doi:10.1038/s41598-025-09113-9 · Cited by 3 · see citing works
Li, D.-J., Tsai, S., Chen, T.-J., Kao, Y.-C., Liang, C.-S., & Chen, M.-H. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.04.071 · Cited by 3 · see citing works
Chang, X.-L., Wang, Y., Hou, Y., Cheng, W., & Chen, S.-Z. (2024) · Brain and Behavior · doi:10.1002/brb3.70045 · Cited by 3 · see citing works
“However, Western medicine approaches for treating depression are limited in clinical practice due to side effects such as gastrointestinal reactions, sleepiness, and suicidal tendencies (Kverno & Mangano, 2021).”
BackgroundCrișan, C., Stretea, R., Bonea, M., Fîntînari, V., Țața, I.-M., Stan, A., Micluția, I., Cherecheș, R., & Milhem, Z. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14050519 · Cited by 3 · see citing works
“In severe cases, treatments like electroconvulsive therapy or transcranial magnetic stimulations may be considered [17–19].”
BackgroundBernanke, A., Hasley, R., Sabetfakhri, N., de Wit, H., Smith, B. M., Wang, L., Brenner, L. A., Hanlon, C., Philip, N. S., Ajilore, O., et al. (2024) · JMIR Research Protocols · doi:10.2196/58206 · Cited by 2 · see citing works
“Furthermore, many patients will require multiple medication trials and may take months to experience any symptomatic improvement [36].”
Mood food: antidepressant effects of culinary spices
Zhong, L.-Q., Qing, Y.-J., & Liu, J. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1790721 · Cited by 2 · see citing works
D'Aprile, I., Petrillo, G., Begni, V., Creutzberg, K., Orso, R., Grassi-Oliveira, R., Riva, M. A., & Cattaneo, A. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03622-x · Cited by 2 · see citing works
“Although different treatment options are available, about 30 – 50% of patients do not respond [3], and some of them develop treatment resistant depression, overall indicating the urgent need to identify novel targets for interventions.”
Zhao, G.-G., Zhao, J., Kong, Y., Pang, Y.-Y., Zheng, X., & Zhang, Y.-W. (2025) · World Journal of Psychiatry · doi:10.5498/wjp.v15.i9.109458 · Cited by 2 · see citing works
He, G., Xi, M., Zhang, T., Wang, S., & Liu, G. (2025) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2025.101378 · Cited by 2 · see citing works
“Ket, a fast-acting antidepressant, has been widely studied and recognized for its potential in the treatment of mental disorders [9,42].”
Liang, P., Chen, J.-J., Yang, X., Long, R., Li, Y., Wang, Z., Yang, P., & Liang, Y.-D. (2025) · World Journal of Psychiatry · doi:10.5498/wjp.v15.i4.102182 · Cited by 2 · see citing works
Kipfer, A., Laatikainen, T., Partonen, T., Roponen, J., Nuutinen, O., & Lamidi, M.-L. (2025) · Journal of Affective Disorders Reports · doi:10.1016/j.jadr.2025.100914 · Cited by 2 · see citing works
Mondragón-García, A., Ramírez-Sánchez, E., Francia-Ramírez, D., Hernández-González, O., Rojano-Posada, Y., Ortega-Tinoco, S., Garduño, J., Verdugo-Díaz, L., & Hernández-López, S. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.10.043 · Cited by 2 · see citing works
“…approach relies on the use of selective serotonin reuptake inhibitors (SSRIs), although notably, around 30 % of patients treated with SSRIs exhibit resistance to this first-line treatment (Papakostas and Fava, 2010; Kverno and Mangano, 2021; Borb ´ ely et al., 2022; Nu ˜ nez et al., 2022).”
Pan, Y.-J., Yeh, L.-L., & Kuo, K. (2024) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2024.104091 · Cited by 2 · see citing works
Psychiatric and legal considerations for ketamine treatment within prison settings
Bayrhammer-Savel, M., Ortner, M., Hout, M. V., & Komorowski, A. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1316108 · Cited by 2 · see citing works
Pan, Y.-J., & Yeh, L.-L. (2023) · Australian and New Zealand journal of psychiatry (Print) · doi:10.1177/00048674221145337 · Cited by 2 · see citing works
“Research has also indicated that approximately 30% of patients treated for a major depressive episode did not achieve remission after receiving two or more first-line antidepressant treatments (Kverno and Mangano, 2021).”
BackgroundPoidasheva, A. G., Sinitsyn, D., Bakulin, I., Suponeva, N., & Piradov, M. (2022) · Neurology, neuropsychiatry, Psychosomatics · doi:10.14412/2074-2711-2022-4-12-19 · Cited by 2 · see citing works
Anghel, C. E., Băcilă, C., Vintilă, B., Cornea, M., Grama, A.-M., Macavei, B.-M., Lomnășan, A., Roman-Filip, I., & Roman-Filip, C. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15155890 · Cited by 1 · see citing works
“Approximately 30% of individuals diagnosed with major depressive episodes will experience TRD [5].”
Han, Y.-D., Yan, H.-H., Guo, W., & Cao, H.-Y. (2026) · Neurotherapeutics · doi:10.1016/j.neurot.2026.e00932 · Cited by 1 · see citing works
“Approximately 20 – 30% of patients with MDD develop TRD, typically defined as the failure to achieve clinical response following at least two adequate antidepressant trials [1,2].”
InfluentialVilela-Filho, O., Bannach, M., Lino-Filho, A. M., Hamani, C., Nuttin, B., Hariz, M., Schulder, M., Greenberg, B. D., Cosgrove, R., de Oliveira-Souza, R., et al. (2026) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2025-337800 · Cited by 1 · see citing works
Ding, X.-T., Wu, Y.-P., Yang, J., Zhu, G.-H., & Sun, H.-W. (2026) · Psychopathology · doi:10.1159/000551413 · Cited by 1 · see citing works
“Critically, approximately 30% of patients develop TRD with inadequate conventional antidepressant response [7], necessitating urgent development of rapid-acting alternatives like ketamine, whose NMDA receptor antagonism enables rapid synaptic remodeling and significant clinical potential for TRD…”
Marx, L., Sen, Z., Danyeli, L., Li, M., Brigadski, T., Lessmann, V., & Walter, M. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1662051 · Cited by 1 · see citing works
Sun, W.-X., Pan, X., Yang, H.-D., Wang, X.-Y., Zhang, X.-Y., Pan, S.-M., Li, Z., & Zhang, X.-B. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.120122 · Cited by 1 · see citing works
Erdelyi-Hamza, B., Torok, D., Krause, S., Eszlari, N., Bagdy, G., Juhász, G., & Gonda, X. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.119731 · Cited by 1 · see citing works
Dalhuisen, I., Biemans, T., Vos, C., ter Hark, S. T., van Oostrom, I., Spijker, J., Wijnen, B., van Exel, E. V., van Mierlo, H., de Waardt, D. D., et al. (2025) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-025-02012-0 · Cited by 1 · see citing works
“Up to 35% of patients fail to respond to two trials of first-line treatments and are considered to have treatment-resistant depression (TRD) [ 4 ].”
Wang, J.-L., Wang, J.-J., Zhang, C.-X., & Li, G.-F. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1531496 · Cited by 1 · see citing works
Yin, X.-J., & Wang, X.-Y. (2025) · Journal of physiological investigation · doi:10.4103/ejpi.ejpi-d-24-00064 · Cited by 1 · see citing works
The role of psilocybin in depressive disorders
Najib, J. (2024) · Current Medical Research and Opinion · doi:10.1080/03007995.2024.2396536 · Cited by 1 · see citing works
“Additionally, the prevalence of treatment-resistant depression is noted to be 10%–30% 12,58 .”
Ning, B.-L., Wang, Z., Yang, Q., Wu, Q., Deng, Q., Gao, J.-F., Fu, W., Deng, Y., Wu, B.-X., Huang, X.-C., et al. (2024) · World Journal of Acupuncture - Moxibustion · doi:10.1016/j.wjam.2024.03.002 · Cited by 1 · see citing works
We Are Their Hope: Addressing Mental Health Barriers Through Advocacy.
Kowalczyk, A. (2023) · Journal of Psychosocial Nursing and Mental Health Services · doi:10.3928/02793695-20230818-01 · Cited by 1
Gawłowska, K., Nowakowska, K., Makówka, J., Bajurny, W., Góral, M. P., Bocheńska, A., Kopecki, S. D., Grodzińska, W., & Chłopaś-Konowałek, A. (2026) · Molecules · doi:10.3390/molecules31173130
“What is more, in some cases, they are unfortunately insufficient for the management of illnesses [24,25].”
Sugimori, Y., Yano, Y., Asano, T., Suzuki, S., Kaigawa, T., Yokose, J., Shigetsura, Y., Muramatsu, S.-I., & Nitta, A. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111148
Vasileiadi, M., Nona, C., Silver, D., Jo, D., Musa, L., Giacobbe, P., Lipsman, N., Chinchilla, C., Kim, D. Y., Kang, S.-W., et al. (2026) · Clinical Neurophysiology · doi:10.1016/j.clinph.2026.2112396
Gyorik, D., Torok, D., Bagdy, G., Juhász, G., & Gonda, X. (2026) · Dialogues in Clinical Neuroscience · doi:10.1080/19585969.2026.2702037
- Authors
- Kverno, K. S., & Mangano, E.
- Venue
- Journal of Psychosocial Nursing and Mental Health Services
- Publisher
- SLACK, Inc.
- Published
- 2021-09
- Volume
- 59
- Issue
- 9
- Pages
- 7-11
- ISSN
- 0279-3695 (ISSN-L)
- 1938-2413
- OpenAlex
- W3196802696
- Cited by
- 121
- References
- 0
- Citations by year
- 2026: 13 · 2025: 30 · 2024: 36 · 2023: 32 · 2022: 9 · 2017: 1
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychosocial Nursing and Mental Health Services (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Keywords
- treatment-resistant depression, major depressive disorder, antidepressant treatment, esketamine, psilocybin, pramipexole, depression subtypes, depression remission
- MeSH terms
- Antidepressive Agents, Depression, Major Depressive Disorder, Drug Therapy, Combination, Humans, Depressive Disorder, Treatment-Resistant
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