The DOI matches its Crossref record, with a small difference in title or year; 50 of the 51 references it cites were found in a registry or an index.
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial
Open accessAbstract
Importance: Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants. Objective: To assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD). Design, Setting, and Participants: This phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study was conducted in multiple outpatient referral centers from January 28, 2014, to September 25, 2015. The study consisted of 4 phases: (1) screening, (2) double-blind treatment (days 1-15), composed of two 1-week periods, (3) optional open-label treatment (days 15-74), and (4) posttreatment follow-up (8 weeks). One hundred twenty-six adults with a DSM-IV-TR diagnosis of MDD and history of inadequate response to 2 or more antidepressants (ie, TRD) were screened, 67 were randomized, and 60 completed both double-blind periods. Intent-to-treat analysis was used in evaluation of the findings. Interventions: In period 1, participants were randomized (3:1:1:1) to placebo (n = 33), esketamine 28 mg (n = 11), 56 mg (n = 11), or 84 mg (n = 12) twice weekly. In period 2, 28 placebo-treated participants with moderate-to-severe symptoms were rerandomized (1:1:1:1) to 1 of the 4 treatment arms; those with mild symptoms continued receiving placebo. Participants continued their existing antidepressant treatment during the study. During the open-label phase, dosing frequency was reduced from twice weekly to weekly, and then to every 2 weeks. Main Outcomes and Measures: The primary efficacy end point was change from baseline to day 8 (each period) in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Results: Sixty-seven participants (38 women, mean [SD] age, 44.7 [10.0] years) were included in the efficacy and safety analyses. Change (least squares mean [SE] difference vs placebo) in MADRS total score (both periods combined) in all 3 esketamine groups was superior to placebo (esketamine 28 mg: -4.2 [2.09], P = .02; 56 mg: -6.3 [2.07], P = .001; 84 mg: -9.0 [2.13], P < .001), with a significant ascending dose-response relationship (P < .001). Improvement in depressive symptoms appeared to be sustained (-7.2 [1.84]) despite reduced dosing frequency in the open-label phase. Three of 56 (5%) esketamine-treated participants during the double-blind phase vs none receiving placebo and 1 of 57 participants (2%) during the open-label phase had adverse events that led to study discontinuation (1 event each of syncope, headache, dissociative syndrome, and ectopic pregnancy). Conclusions and Relevance: In this first clinical study to date of intranasal esketamine for TRD, antidepressant effect was rapid in onset and dose related. Response appeared to persist for more than 2 months with a lower dosing frequency. Results support further investigation in larger trials. Trial Registration: clinicaltrials.gov identifier: NCT01998958.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, formulations of ketamine are also being developed, and intranasal esketamine spray has shown high efficacy in treating MDD. 484”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [484]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A breakthrough in the treatment of depression was the discovery that the anesthetic (R,S)-ketamine (ketamine), when administered at sub-anesthetic doses, elicits rapid (sometimes within hours) antidepressant effects in humans that are otherwise resistant to monoaminergic-acting therapies.”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Daly et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This study observed a similar rapid reduction (within two hours) in depression symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) following an intranasal (S)-ketamine treatment (28 or 84 mg), which separated from placebo even at one week following a single administration.”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Daly et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Unlike IV ketamine, there are also data demonstrating long- term (i.e., greater than 3- year) safety and tolerability for esketamine 194,195 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [194]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Intranasal esketamine spray co- initi ated with an antidepressant has also demonstrated rapid clinically meaningful efficacy in patients with TRD.”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [194]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Our findings are concordant with the direction and general magnitude of effect reported in pivotal trials of adjunctive intranasal esketamine in TRD and the relapse-prevention study (18–23)”
From Intranasal esketamine plus oral antidepressant for treatment-resistant depression: acute induction and maintenance relapse-prevention outcomes in a systematic review and meta-analysis (2026) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Results were consistent with previous findings from completed short-term (4-week) phase 2 and 3 studies.10,12,15”
From Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial (2019) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Earlier studies of esketamine in patients with treatmentresistant depression (10,11) and major depression at imminent risk for suicide (12), which demonstrated greater magnitude of early response, applied a less stringent definition for response onset and employed site-based raters for efficacy evaluation.”
From Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study (2019) · cites this paper as [11]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Among these, six were initiation studies (1 with a 1-week duration [40], five with a 4-week duration [9–11, 41, 42] and one was a continuation study [12].”
The cited source says what the claim attributes to it.
In the citing paper
“We verified the positive efficacy at 1 week in NCT01998958 [40] but could not compare 4 out of 10 analyses due to unpublished results.”
The cited source says what the claim attributes to it.
In the citing paper
“The sample size planned for this study was calculated assuming a treatment difference for the double-blind treatment phase of 6.5 points in MADRS score between the esketamine plus antidepressant group and the antidepressant plus placebo group and a standard deviation of 12, based on the results of a phase 2 study of esketamine nasal spray for treatment-resistant depression (11) and clinical”
The cited source says what the claim attributes to it.
In the citing paper
“The magnitude of postdose blood pressure increases was lower compared with the previous phase 2 study of esketamine nasal spray (11), possibly because of the riskmitigation blood pressure guidelines initiated in phase 3 studies (see the online supplement).”
In the citing paper
“The approvals of esketamine nasal spray were based on efficacy and safety findings from phase 2/3 studies of TRD treatment for 4 weeks to 1 year [9–14].”
In the citing paper
“In addition, intranasal administration of 28–84 mg (S)-ketamine twice a week for a total period of two weeks induced antidepressant actions in treatment-resistant depressed patients as an adjunct treatment 119.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [119]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A Brief Measure for Assessing Generalized Anxiety Disorder: The GAD-7
Spitzer, R. L., Kroenke, K., Williams, J. B. W., & Löwe, B. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.10.1092 · Cited by 31,765
Diagnostic and Statistical Manual of Mental Disorders.
Widiger, T. A. (2000) · Oxford University Press eBooks · doi:10.1037/10518-009 · Cited by 19,766
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962
The Brief Psychiatric Rating Scale.
Overall, J. E., & Gorham, D. R. (1962) · Psychological Reports · doi:10.2466/pr0.1962.10.3.799 · Cited by 11,090
Cook, R. J., Dickens, B. M., & Fathalla, M. F. (2003) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199241323.003.0025 · Cited by 10,825
(1976) · Medical Entomology and Zoology · Cited by 8,899
Vos, T., Barber, R. M., Bell, B., Bertozzi-Villa, A., Biryukov, S., Bolliger, I., Charlson, F., Davis, A., Degenhardt, L., Dicker, D., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(15)60692-4 · Cited by 6,414
Antidepressant effects of ketamine in depressed patients
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00230-9 · Cited by 3,856
Rush, A. J., Trivedi, M. H., Ibrahim, H. M., Carmody, T. J., Arnow, B., Klein, D. N., Markowitz, J. C., Ninan, P. T., Kornstein, S., Manber, R., et al. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01866-8 · Cited by 3,829
Self-citation
Cited by
Sorted by citations
Items 101–200 of 714
Yokoyama, R., Higuchi, M., Tanabe, W., Tsukada, S., Naito, M., Yamaguchi, T., Chen, L., Kasai, A., Seiriki, K., Nakazawa, T., et al. (2020) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2020.172876 · Cited by 65
Signature-based approaches for informed drug repurposing: targeting CNS disorders
Shukla, R., Henkel, N., Alganem, K., Hamoud, A.-R. A., Reigle, J. K., Alnafisah, R. S., Eby, H., Imami, A. S., Creeden, J. F., Miruzzi, S. A., et al. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0752-6 · Cited by 66
Chen, G., Chen, L., Zhang, Y., Li, X., Lane, R., Lim, P., Daly, E. J., Furey, M. L., Fedgchin, M., Popova, V., et al. (2022) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyab084 · Cited by 66
Self-citationKetamine as a therapeutic agent for depression and pain: mechanisms and evidence
Subramanian, S., Haroutounian, S., Palanca, B. J. A., & Lenze, E. J. (2022) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2022.120152 · Cited by 73
An update on NMDA antagonists in depression
Pochwat, B., Nowak, G., & Szewczyk, B. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1643237 · Cited by 67
Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat
Jefsen, O. H., Højgaard, K., Christiansen, S. L., Elfving, B., Nutt, D., Wegener, G., & Müller, H. K. (2019) · Acta Neuropsychiatrica · doi:10.1017/neu.2019.15 · Cited by 64
Wang, W., Xu, H., Ling, B., Chen, Q., Lv, J., & Yu, W. (2022) · Medicine · doi:10.1097/md.0000000000032010 · Cited by 62
Leal, G. C., Souza-Marques, B., Mello, R. P., Bandeira, I. D., Caliman-Fontes, A. T., Carneiro, B. A., Faria-Guimarães, D., Guerreiro-Costa, L. N. F., Jesus-Nunes, A. P., Silva, S. S., et al. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.02.151 · Cited by 62
Tian, Z. R., Dong, C., Fujita, A., Fujita, Y., & Hashimoto, K. (2018) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2018.07.003 · Cited by 63
Prognosis and Improved Outcomes in Major Depression: A Review
Kraus, C., Kadriu, B., Lanzenberger, R. R., Zarate, C. A., & Kasper, S. F. (2020) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.18205 · Cited by 64
Chronic administration of ketamine induces cognitive deterioration by restraining synaptic signaling
Luo, Y., Yang, Y., Zhang, M., He, H., & Fan, N. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0793-6 · Cited by 62
New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview
Bortolozzi, A. A., Fico, G., Berk, M., Solmi, M., Fornaro, M., Quevedo, J., Zarate, C. A., Kessing, L. V., Vieta, E., & Carvalho, A. F. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000007 · Cited by 68
McIntyre, R. S., Millson, B., & Power, G. S. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.07.045 · Cited by 60
Pettorruso, M., Guidotti, R., d’Andrea, G., Risio, L. D., D’Andrea, A., Chiappini, S., Carullo, R., Barlati, S., Zanardi, R., Rosso, G., et al. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115378 · Cited by 60
Kawczak, P., Feszak, I. J., & Bączek, T. (2024) · Biomedicines · doi:10.3390/biomedicines12102283 · Cited by 66
Meerman, J. J., ter Hark, S. E., Janzing, J., & Coenen, M. J. H. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.02.015 · Cited by 62
Takahashi, N., Yamada, A., Shiraishi, A., Shimizu, H., Goto, R., & Tominaga, Y. (2021) · BMC Psychiatry · doi:10.1186/s12888-021-03538-y · Cited by 57
Zhou, Y., Lan, X., Wang, C., Zhang, F., Liu, H., Fu, L., Li, W., Ye, Y., Hu, Z., Chao, Z., et al. (2023) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2023.05.031 · Cited by 60
Costi, S., Soleimani, L., Glasgow, A., Brallier, J., Spivack, J., Schwartz, J., Levitch, C. F., Richards, S., Hoch, M., Stade, E. C., et al. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0365-0 · Cited by 56
The role of eEF2 kinase in the rapid antidepressant actions of ketamine
(2020) · Advances in Pharmacology · doi:10.1016/bs.apha.2020.04.005 · Cited by 52
Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial
Janik, A., Qiu, X., Lane, R., Popova, V., Drevets, W. C., Canuso, C. M., Macaluso, M., Mattingly, G. W., Shelton, R. C., Zajecka, J. M., et al. (2025) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2025.1317 · Cited by 54
Self-citationd’Andrea, G., Pettorruso, M., Lorenzo, G. D., Rhee, T. G., Chiappini, S., Carullo, R., Barlati, S., Zanardi, R., Rosso, G., Nicola, M. D., et al. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.12.038 · Cited by 55
Enhanced ERK activity extends ketamine’s antidepressant effects by augmenting synaptic plasticity
Ma, Z., Guzikowski, N. J., Kim, J., Kavalali, E. T., & Monteggia, L. M. (2025) · Science · doi:10.1126/science.abb6748 · Cited by 54
Esketamine for treatment resistant depression: a trick of smoke and mirrors?
Gastaldon, C., Papola, D., Ostuzzi, G., & Barbui, C. (2020) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796019000751 · Cited by 54
“The authors of the three studies reported that a difference of at least 6.5 points at MADRS between esketamine and placebo should be observed to make a claim of clinical significance (Daly et al., 2019), based on the results of phase II studies (Daly et al., 2017).”
BackgroundInfluentialRole of mental state in temporomandibular disorders: A review of the literature
Florjański, W., & Winiewska, S. (2021) · Dental and Medical Problems · doi:10.17219/dmp/132978 · Cited by 52
Wang, S., Kim, N.-Y., Na, H.-R., Lim, H. K., Woo, Y. S., Pae, C., & Bahk, W. (2021) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2021.19.2.341 · Cited by 61
Suzuki, K., Kim, J.-W., Nosyreva, E., Kavalali, E. T., & Monteggia, L. M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109918 · Cited by 49
Seshadri, A., Prokop, L. J., & Singh, B. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.03.137 · Cited by 55
Wu, M., Minkowicz, S., Dumrongprechachan, V., Hamilton, P., Xiao, L., & Kozorovitskiy, Y. (2021) · eLife · doi:10.7554/elife.64041 · Cited by 54
Reporting of harms in clinical trials of esketamine in depression: a systematic review
de Laportalière, T. T., Jullien, A., Yrondi, A., Cestac, P., & Montastruc, F. (2023) · Psychological Medicine · doi:10.1017/s0033291723001058 · Cited by 26
New and emerging treatments for major depressive disorder
Njenga, C., Ramanuj, P., de Magalhães, F. J. C., & Pincus, H. A. (2024) · BMJ · doi:10.1136/bmj-2022-073823 · Cited by 51
Targeting metaplasticity mechanisms to promote sustained antidepressant actions
Brown, K. A., & Gould, T. D. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02397-1 · Cited by 49
Deppe, M., Abdelnaim, M. A., Hebel, T., Kreuzer, P. M., Poeppl, T. B., Langguth, B., & Schecklmann, M. (2020) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-020-01160-9 · Cited by 51
Li, Y., Wu, H., Jiang, X., Dong, Y.-F., Zheng, J., & Gao, J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.04.001 · Cited by 47
Deyama, S., & Kaneda, K. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109335 · Cited by 46
Falchi-Carvalho, M., Palhano-Fontes, F., Wießner, I., Barros, H., Bolcont, R., Laborde, S., Silva, S. R. B., Montanini, D., Barbosa, D. C., Teixeira, E., et al. (2025) · Neuropsychopharmacology · doi:10.1038/s41386-025-02091-6 · Cited by 52
Genome-wide association study and polygenic risk score analysis of esketamine treatment response
Li, Q. S., Wajs, E., Ochs-Ross, R., Singh, J. B., & Drevets, W. C. (2020) · Scientific Reports · doi:10.1038/s41598-020-69291-6 · Cited by 49
Self-citationAn Update on Glutamatergic System in Suicidal Depression and on the Role of Esketamine
Berardis, D. D., Tomasetti, C., Pompili, M., Serafini, G., Vellante, F., Fornaro, M., Valchera, A., Perna, G., Volpe, U., Martinotti, G., et al. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200131100316 · Cited by 46
An, D., Wei, C., Wang, J., & Wu, A. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.648691 · Cited by 45
Van Amsterdam, J., & Van Den Brink, W. (2022) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2021.1949454 · Cited by 44
(R)‐ and (S)‐ketamine induce differential fMRI responses in conscious rats
Masaki, Y., Kashiwagi, Y., Watabe, H., & Abe, K. (2019) · Synapse · doi:10.1002/syn.22126 · Cited by 44
Ng, J., Rosenblat, J. D., Lui, L. M. W., Teopiz, K. M., Lee, Y. L., Lipsitz, O., Mansur, R. B., Rodrigues, N. B., Nasri, F., Gill, H., et al. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.06.032 · Cited by 47
Antidepressants and nose-to-brain delivery: drivers, restraints, opportunities and challenges
Vitorino, C., Silva, S., Bicker, J., Falcão, A. C., & Fortuna, A. C. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.06.001 · Cited by 43
Ochs-Ross, R., Wajs, E., Daly, E., Zhang, Y., Lane, R., Lim, P., Drevets, W. C., Steffens, D. C., Sanacora, G., Jamieson, C., et al. (2021) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2021.09.014 · Cited by 44
Self-citationDean, R. L., Hurducas, C., Hawton, K., Spyridi, S., Cowen, P. J., Hollingsworth, S., Marquardt, T., Barnes, A., Smith, R., McShane, R., et al. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011612.pub3 · Cited by 95
Kraus, C., Kautzky, A., Watzal, V., Gramser, A., Kadriu, B., Deng, Z., Bartova, L., Zarate, C. A., Lanzenberger, R. R., Souery, D., et al. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.05.042 · Cited by 45
Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives
Shin, C., & Kim, Y. (2020) · Psychiatry Investigation · doi:10.30773/pi.2019.0236 · Cited by 47
Ketamine for Treatment of Mood Disorders and Suicidality: A Narrative Review of Recent Progress
Kritzer, M. D., Mischel, N., Young, J. R., Lai, C. S., Masand, P. S., Szabo, S. T., & Mathew, S. J. (2021) · Annals of Clinical Psychiatry · doi:10.12788/acp.0048 · Cited by 43
Mertens, L. J., Koslowski, M., Betzler, F., Evens, R., Gilles, M., Jungaberle, A., Jungaberle, H., Majić, T., Ströhle, A., Wolff, M., et al. (2022) · Neuroscience Applied · doi:10.1016/j.nsa.2022.100104 · Cited by 41
Suicide Has Many Faces, So Does Ketamine: a Narrative Review on Ketamine’s Antisuicidal Actions
Lengvenytė, A., Olié, É., & Courtet, P. (2019) · Current Psychiatry Reports · doi:10.1007/s11920-019-1108-y · Cited by 40
d’Andrea, G., Chiappini, S., McIntyre, R. S., Stefanelli, G., Carullo, R., Andriola, I., Zanardi, R., Martiadis, V., Sensi, S. L., Sani, G., et al. (2023) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2023.06.016 · Cited by 42
Conley, A. A., Norwood, A. E. Q., Hatvany, T. C., Griffith, J. D., & Barber, K. E. (2021) · Psychopharmacology · doi:10.1007/s00213-021-05825-8 · Cited by 39
Bortolozzi, A., Manashirov, S., Chen, A., & Artigas, F. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107873 · Cited by 37
Personalized use of ketamine and esketamine for treatment-resistant depression
Medeiros, G. C., Demo, I., Goes, F. S., Zarate, C. A., & Gould, T. D. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03180-8 · Cited by 43
Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study
Zaki, N., Chen, L., Lane, R., Doherty, T., Drevets, W. C., Morrison, R. L., Sanacora, G., Wilkinson, S. T., Young, A. H., Lacerda, A. L. T., et al. (2025) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaf027 · Cited by 46
Self-citationSmith-Apeldoorn, S. Y., Veraart, J. K. E., Kamphuis, J., van Asselt, A. D. I., Touw, D. J., Rot, M. A. H., & Schoevers, R. A. (2019) · BMC Psychiatry · doi:10.1186/s12888-019-2359-1 · Cited by 44
Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses
Lima, T. D. M., Visacri, M. B., & Aguiar, P. M. (2021) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-021-03216-8 · Cited by 43
Psiuk, D., Nowak, E., Dycha, N., Łopuszańska, U., Kurzepa, J., & Samardakiewicz, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911450 · Cited by 46
Wang, H., Liu, S., Sun, Y., Chen, C., Hu, Z., Li, Q., Long, J., Yan, Q., Liang, J., Lin, Y., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102472 · Cited by 39
DePierro, J. M., Lepow, L., Feder, A., & Yehuda, R. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.07.009 · Cited by 41
Sahib, A. K., Loureiro, J. R., Vasavada, M. M., Kubicki, A., Wade, B., Joshi, S. H., Woods, R. P., Congdon, E. L., Espinoza, R. T., & Narr, K. L. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00947-7 · Cited by 37
Is (S)-norketamine an alternative antidepressant for esketamine?
Hashimoto, K., & Yang, C. (2019) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-018-0922-2 · Cited by 37
What Is New about New Antidepressants?
Dubovsky, S. L. (2018) · Psychotherapy and Psychosomatics · doi:10.1159/000488945 · Cited by 37
Addictive potential of novel treatments for refractory depression and anxiety
Kolar, D. (2018) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s167538 · Cited by 37
Lucchese, A. C., Sarin, L. M., Magalhães, E. T. P., Sant, L. C. D., Puertas, C. B., Tuena, M. A., Nakahira, C., Fava, V. A. R., Delfino, R. S., Surjan, J. C., et al. (2021) · Journal of Psychopharmacology · doi:10.1177/0269881120978398 · Cited by 36
Intranasal esketamine: From origins to future implications in treatment-resistant depression
Sanders, B. J., & Brula, A. Q. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.02.020 · Cited by 37
Artin, H., Bentley, S., Mehaffey, E., Liu, F. X., Sojourner, K., Bismark, A. W., Printz, D., Lee, E., Martis, B., Peralta, S. D., et al. (2022) · EClinicalMedicine · doi:10.1016/j.eclinm.2022.101439 · Cited by 38
Chen, X., Hou, X., Bai, D., Lane, R., Zhang, C., Canuso, C., Wang, G., & Fu, D.-J. (2023) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s391096 · Cited by 35
Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats
Ianni, T. D., Ewbank, S. N., Levinstein, M. R., Azadian, M. M., Budinich, R. C., Michaelides, M., & Airan, R. D. (2024) · Nature Communications · doi:10.1038/s41467-024-45157-7 · Cited by 33
Xue, S., Xue, F., Ma, Q., Wang, S., Wang, Y., Tan, Q., Wang, H., Zhou, C., & Peng, Z. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.172738 · Cited by 38
Treatment resistant depression in women with peripartum depression
Cepeda, M. S., Kern, D. M., & Nicholson, S. (2019) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-019-2462-9 · Cited by 31
Salloum, N. C., D, M. F. M., Hock, R. S., Freeman, M. P., Flynn, M., Hoeppner, B. B., Cusin, C., Iosifescu, D. V., Trivedi, M. H., Sanacora, G., et al. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.09.017 · Cited by 34
Saad, Z. S., Hibar, D. P., Fedgchin, M. M., Popova, V., Furey, M. L., Singh, J. B., Kolb, H. C., Drevets, W. C., & Chen, G. (2020) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaa030 · Cited by 34
Self-citationModulation of the functional connectome in major depressive disorder by ketamine therapy
Sahib, A. K., Loureiro, J. R., Vasavada, M. M., Anderson, C., Kubicki, A., Wade, B., Joshi, S. H., Woods, R. P., Congdon, E. L., Espinoza, R. T., et al. (2020) · Psychological Medicine · doi:10.1017/s0033291720004560 · Cited by 35
Ng, J., Lui, L. M. W., Rosenblat, J. D., Teopiz, K. M., Lipsitz, O., Cha, D. S., Xiong, J., Nasri, F., Lee, Y. L., Kratiuk, K., et al. (2021) · Psychopharmacology · doi:10.1007/s00213-021-05767-1 · Cited by 34
Jones, R., Freeman, M. P., Kornstein, S. G., Cooper, K., Daly, E., Canuso, C. M., & Nicholson, S. (2022) · Archives of Women s Mental Health · doi:10.1007/s00737-021-01185-6 · Cited by 33
Self-citationHavlik, J. L., Wahid, S., Teopiz, K. M., McIntyre, R. S., Krystal, J. H., & Rhee, T. G. (2024) · Current Psychiatry Reports · doi:10.1007/s11920-024-01494-4 · Cited by 35
Terao, I., Tsuge, T., Endo, K., & Kodama, W. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.11.023 · Cited by 33
Ketamine – A New Antidepressant Drug with Anti-Inflammatory Properties
Jóźwiak-Bębenista, M., Sokołowska, P., Wiktorowska‐Owczarek, A., Kowalczyk, E., & Sienkiewicz, M. (2023) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.123.001823 · Cited by 33
Bleibel, L., Sokołowska, P., Henrykowska, G. A., Owczarek, J., & Wiktorowska‐Owczarek, A. (2025) · Pharmaceuticals · doi:10.3390/ph18060867 · Cited by 37
Repurposing Potential of Ketamine: Opportunities and Challenges
Gautam, C. S., Mahajan, S. S., Sharma, J., Singh, H., & Singh, J. (2019) · Indian Journal of Psychological Medicine · doi:10.4103/ijpsym.ijpsym_228_19 · Cited by 32
Self-citationVlerick, L., Devreese, M., Peremans, K. Y., Dockx, R., Croubels, S., Duchateau, L., & Polis, I. (2020) · PLoS ONE · doi:10.1371/journal.pone.0227762 · Cited by 32
Ketamine for depression clinical issues
Iqbal, S., & Mathew, S. J. (2020) · Advances in pharmacology · doi:10.1016/bs.apha.2020.02.005 · Cited by 33
Xue, S., Zhou, C., Xue, F., Liu, L., Cai, Y., Luo, J., Wang, Y., Tan, Q., Wang, H., & Peng, Z. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109946 · Cited by 32
Domany, Y., & McCullumsmith, C. B. (2021) · Archives of Suicide Research · doi:10.1080/13811118.2021.1878078 · Cited by 33
Okada, M., Kawano, Y., Fukuyama, K., Motomura, E., & Shiroyama, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217951 · Cited by 32
Pearson, C., Siegel, J. S., & Gold, J. A. (2021) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2021.120096 · Cited by 34
A New Paradigm for Achieving a Rapid Antidepressant Response
Malhi, G. S., Morris, G., Bell, E., & Hamilton, A. (2020) · Drugs · doi:10.1007/s40265-020-01303-1 · Cited by 33
Managing dissociative symptoms following the use of esketamine nasal spray: a case report
Pereira, S., Brennan, E. A., Patel, A. B., Moran, M., Wallier, J., & Liebowitz, M. R. (2020) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000327 · Cited by 30
Treatments for Self-Injurious Thoughts and Behaviors in Youth: Progress and Challenges
Bettis, A. H., Liu, R. T., Walsh, B. W., & Klonsky, E. D. (2020) · Evidence-Based Practice in Child and Adolescent Mental Health · doi:10.1080/23794925.2020.1806759 · Cited by 32
The Role of Glutamate Underlying Treatment-resistant Depression
Kim, J., Kim, T.-E., Lee, S., & Koo, J. W. (2023) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.22.1034 · Cited by 34
Okada, M., Fukuyama, K., Nakano, T., & Ueda, Y. (2019) · Biomolecules · doi:10.3390/biom9110746 · Cited by 29
Urothelial toxicity of esketamine in the treatment of depression
Findeis, H., Sauer, C., Cleare, A. J., Bauer, M., & Ritter, P. S. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05611-y · Cited by 29
Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success?
Carboni, E., Carta, A. R., Carboni, E., & Novelli, A. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.657714 · Cited by 33
A key requirement for synaptic Reelin signaling in ketamine-mediated behavioral and synaptic action
Kim, J., Herz, J., Kavalali, E. T., & Monteggia, L. M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2103079118 · Cited by 29
Capuzzi, E., Caldiroli, A., Capellazzi, M., Tagliabue, I., Marcatili, M., Colmegna, F., Clerici, M., Buoli, M., & Dakanalis, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179338 · Cited by 37
Drevets, W. C., Bhattacharya, A., & Furey, M. L. (2020) · Advances in pharmacology · doi:10.1016/bs.apha.2020.04.002 · Cited by 29
Self-citationKeeping up with the clinical advances: depression
Ragguett, R.-M., Tamura, J. K., & McIntyre, R. S. (2019) · CNS Spectrums · doi:10.1017/s1092852919001159 · Cited by 27
Yang, S., Wang, J., Li, X., Wang, T., Xu, Z., Xu, X. M., Zhou, X., & Chen, G. (2021) · Psychiatric Quarterly · doi:10.1007/s11126-020-09871-x · Cited by 27
Boudieu, L., Mennetrier, M., Llorca, P., & Samalin, L. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15122773 · Cited by 31
Metadata
- Authors
- Daly, E. J., Singh, J. B., Fedgchin, M., Cooper, K., Lim, P., Shelton, R. C., Thase, M. E., Winokur, A., Van Nueten, L., Manji, H., & Drevets, W. C.
- Affiliations
- Janssen Research & Development (United States) (US)
- Department of Neuroscience, Janssen Research & Development LLC, San Diego, California
- University of Alabama (US)
- University of Pennsylvania (US)
- UConn Health (US)
- Department of Neuroscience, Janssen Research & Development, Beerse, Belgium
- Corresponding author
- Daly, Ella J.
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2018-02-01
- Volume
- 75
- Issue
- 2
- Pages
- 139
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC5838571
- OpenAlex
- W2779386549
- Semantic Scholar
- b920d61a3ab10c4fbf2f123dd93cb19a9c3872f9
- Cited by
- 718
- References
- 51
- Citations by year
- 2026: 71 · 2025: 99 · 2024: 92 · 2023: 80 · 2022: 75 · 2021: 86 · 2020: 105 · 2019: 70 · 2018: 38
- FWCI
- 40.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- esketamine, treatment-resistant depression, major depressive disorder, intranasal administration, adjunctive therapy, antidepressant resistance, dose-response relationship, antidepressant efficacy, antidepressant safety, adverse events, NMDA receptor antagonists, ketamine derivatives, open-label extension, relapse prevention, treatment-emergent adverse events
- MeSH terms
- Administration, Intranasal, Administration, Oral, Adult, Antidepressive Agents, Major Depressive Disorder, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Ketamine, Male, Middle Aged, Treatment Outcome, Young Adult, Depressive Disorder, Treatment-Resistant
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
