Ketamine vs midazolam: Mood improvement reduces suicidal ideation in depression
Open accessAbstract
Objective Studies demonstrate rapid antidepressant and anti-suicidal ideation effects of subanesthetic ketamine. The specific subcomponents of depression that are most closely tied to reduction of suicidal ideation with ketamine treatment are less explored.Methods Exploratory, post hoc analysis of data from a randomized clinical trial of ketamine vs midazolam in patients with major depressive disorder (MDD) and clinically significant suicidal ideation examined changes in factor analysis-derived symptom clusters from standard measures of depression (Hamilton Depression Rating Scale, HDRS; Beck Depression Inventory, BDI) and mood disturbance (Profile of Mood States, POMS), and their relationship to severity of suicidal ideation (Beck Scale for Suicidal Ideation; SSI). Ratings obtained before and one day after blinded intravenous infusion were decomposed into component factors or published subscales. Treatment effects on factors/subscales were compared between drugs, correlations with changes in suicidal ideation were tested, and stepwise regression was used to derive predictors of change in SSI.Results Factor scores for HDRS Psychic Depression, HDRS Anxiety, BDI Subjective Depression, POMS Depression and POMS Fatigue improved more with ketamine than midazolam. Stepwise regression showed across both drugs that improvement in HDRS Psychic Depression, POMS Depression, and HDRS Anxiety predicted 51.6% of the variance in reduction of suicidal ideation.Limitations Secondary analysis of clinical trial data.Conclusions Ketamine's rapid effects on suicidal ideation appear to be mostly a function of its effects on core mood and anxiety symptoms of MDD, with comparatively little contribution from neurovegetative symptoms with the potential exception of vigor/fatigue.Trial registration Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT01700829.
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
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?
In a clinical experiment, the reduction in thoughts of suicide among MDD patients receiving ketamine was mostly sustained.
“In a clinical experiment, the effect of supplementary injection of subanesthetic doses of ketamine on thoughts of suicide in MDD patients was evaluated, and the results showed that the reduction in thoughts of suicide among MDD patients receiving ketamine was mostly sustained. 481”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [481]
The Methods (Participants; page unavailable) describe a trial of adjunctive subanesthetic intravenous ketamine in patients with MDD and suicidal ideation. The Discussion reports a greater reduction in suicidal ideation than with midazolam one day after treatment, but this analysis does not establish that the reduction in suicidal thoughts was mostly sustained; its reference to a roughly one-week duration of effect is not specific to that outcome. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
An inventory for measuring depression
BECK, A. T. (1961) · Archives of General Psychiatry · doi:10.1001/archpsyc.1961.01710120031004 · Cited by 38,032 · see citing works
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · see citing works
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010 · see citing works
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
Older Adults' Reasons for Using Technology while Aging in Place
Peek, S. T. M., Luijkx, K. G., Rijnaard, M. D., Nieboer, M. E., van der Voort, C. S., Aarts, S., van Hoof, J., Vrijhoef, H. J., & Wouters, E. (2015) · Gerontology · doi:10.1159/000430949 · Cited by 19,803 · see citing works
Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
Kangas, M., Korpelainen, R., Vikman, I., Nyberg, L., & Jämsä, T. J. (2014) · Gerontology · doi:10.1159/000362720 · Cited by 19,003 · see citing works
Assessment of suicidal intention: The Scale for Suicide Ideation.
Beck, A. T., Kovacs, M., & Weissman, A. (1979) · Journal of Consulting and Clinical Psychology · doi:10.1037//0022-006x.47.2.343 · Cited by 3,419 · see citing works
Suicide Prevention Strategies: A Systematic Review
Mann, J. J., Apter, A., Bertolote, J., Beautrais, A., Currier, D., Haas, A., Hegerl, U., Lonnqvist, J., Malone, K., Marusic, A., et al. (2005) · JAMA · doi:10.1001/jama.294.16.2064 · Cited by 2,852 · see citing works
Self-citationBelmaker, R. H., & Agam, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra073096 · Cited by 2,166 · see citing works
Risk factors for suicide in psychiatric outpatients: A 20-year prospective study.
Brown, G. K., Beck, A. T., Steer, R. A., & Grisham, J. R. (2000) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.68.3.371 · Cited by 1,317 · see citing works
Neurobiology of suicidal behaviour
Mann, J. J. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1220 · Cited by 1,260 · see citing works
Self-citationMurrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., Iqbal, S., Pillemer, S., Foulkes, A., Shah, A., et al. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.13030392 · Cited by 1,205 · see citing works
The cellular neurobiology of depression
Manji, H. K., Drevets, W. C., & Charney, D. S. (2001) · Nature Medicine · doi:10.1038/87865 · Cited by 1,182 · see citing works
Bremner, J. D., Krystal, J. H., Putnam, F. W., Southwick, S. M., Marmar, C., Charney, D. S., & Mazure, C. M. (1998) · Journal of Traumatic Stress · doi:10.1023/a:1024465317902 · Cited by 817 · see citing works
Zarate, C. A., Brutsche, N. E., Ibrahim, L., Franco-Chaves, J., Diazgranados, N., Cravchik, A., Selter, J., Marquardt, C. A., Liberty, V., & Luckenbaugh, D. A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.12.010 · Cited by 811 · see citing works
Commentary: Suicide as Psychache
SHNEIDMAN, E. S. (1993) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-199303000-00001 · Cited by 775 · see citing works
LIFE EXPECTANCY AND MORTALITY RATES IN THE UNITED STATES, 1959-2017
Woolf, S., & Schoomaker, H. (2019) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.2019.16932 · Cited by 746 · 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
DiazGranados, N., Ibrahim, L. A., Brutsche, N. E., Ameli, R., Henter, I. D., Luckenbaugh, D. A., Machado-Vieira, R., & Zarate, C. A. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.09m05327blu · Cited by 564 · see citing works
Grunebaum, M. F., Galfalvy, H. C., Choo, T.-H., Keilp, J. G., Moitra, V. K., Parris, M. S., Marver, J. E., Burke, A. K., Milak, M. S., Sublette, M. E., et al. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17060647 · Cited by 431 · see citing works
Self-citationAbdallah, C. G., Sanacora, G., Duman, R. S., & Krystal, J. H. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-053013-062946 · Cited by 422 · see citing works
Suicide Mortality in the United States, 1999-2019
Hedegaard, H. (2021) · doi:10.15620/cdc:101761 · Cited by 412 · see citing works
Fu, D.-J., Ionescu, D. F., Li, X., Lane, R., Lim, P., Sanacora, G., Hough, D., Manji, H., Drevets, W. C., & Canuso, C. M. (2020) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.19m13191 · Cited by 376 · see citing works
Price, R. B., Iosifescu, D. V., Murrough, J. W., Chang, L. C., Al Jurdi, R. K., Iqbal, S. Z., Soleimani, L., Charney, D. S., Foulkes, A. L., & Mathew, S. J. (2014) · Depression and Anxiety · doi:10.1002/da.22253 · Cited by 345 · see citing works
Ketamine Treatment and Global Brain Connectivity in Major Depression
Abdallah, C. G., Averill, L. A., Collins, K. A., Geha, P., Schwartz, J., Averill, C., DeWilde, K. E., Wong, E., Anticevic, A., Tang, C. Y., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.186 · Cited by 300 · see citing works
Gibbons, R. D., Brown, C. H., Hur, K., Davis, J. M., & Mann, J. J. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.2048 · Cited by 291 · see citing works
Self-citationThe timing of antidepressant effects: a comparison of diverse pharmacological and somatic treatments
Machado-Vieira, R., Baumann, J., Wheeler-Castillo, C., Latov, D., Henter, I. D., Salvadore, G., & Zarate, C. A. (2010) · Pharmaceuticals · doi:10.3390/ph3010019 · Cited by 263 · see citing works
Increase in Suicide Mortality in the United States, 1999-2018.
Hedegaard, H. B., Curtin, S. C., & Warner, M. (2020) · PubMed · Cited by 262 · see citing works
Neural correlates of change in major depressive disorder anhedonia following open-label ketamine
Lally, N., Nugent, A. C., Luckenbaugh, D. A., Niciu, M. J., Roiser, J. P., & Zarate, C. A. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881114568041 · Cited by 224 · see citing works
Deaths of Despair and the Future of Capitalism
Case, A. C., & Deaton, A. (2021) · Princeton University Press eBooks · doi:10.2307/j.ctv161f3f8 · Cited by 222 · see citing works
Duman, R. S. (2014) · Depression and Anxiety · doi:10.1002/da.22227 · Cited by 213 · see citing works
Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide
Duman, R. S. (2018) · F1000Research · doi:10.12688/f1000research.14344.1 · Cited by 208 · see citing works
Ionescu, D. F., Bentley, K. H., Eikermann, M., Taylor, N., Akeju, O., Swee, M. B., Pavone, K. J., Petrie, S. R., Dording, C., Mischoulon, D., et al. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.09.037 · Cited by 179 · see citing works
Neuroanatomic Correlates of Psychopathologic Components of Major Depressive Disorder
Milak, M. S., Parsey, R. V., Keilp, J. G., Oquendo, M. A., Malone, K. M., & Mann, J. J. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.4.397 · Cited by 177 · see citing works
Self-citationExploring the psychology of suicidal ideation: a theory driven network analysis.
De Beurs, D., Fried, E. I., Wetherall, K., Cleare, S., O’ Connor, D. B., Ferguson, E., O'Carroll, R. E., & O’ Connor, R. C. (2019) · Behaviour Research and Therapy · doi:10.1016/j.brat.2019.103419 · Cited by 171 · see citing works
Nowak, W., Grendas, L. N., Sanmarco, L. M., Estecho, I. G., Arena, Á. R., Eberhardt, N., Rodante, D. E., Aoki, M. P., Daray, F. M., Carrera Silva, E. A., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.10.063 · Cited by 159 · see citing works
Anhedonia as a clinical correlate of suicidal thoughts in clinical ketamine trials
Ballard, E. D., Wills, K. E., Lally, N., Richards, E. M., Luckenbaugh, D. A., Walls, T. L., Ameli, R., Niciu, M. J., Brutsché, N. E., Park, L., et al. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.04.057 · Cited by 146 · see citing works
Milak, M. S., Proper, C. J., Mulhern, S. T., Parter, A. L., Kegeles, L. S., Ogden, R. T., Mao, X., Rodriguez, C. I., Oquendo, M. A., Suckow, R. F., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.83 · Cited by 144 · see citing works
Self-citationIonescu, D. F., Swee, M. B., Pavone, K. J., Taylor, N., Akeju, O., Baer, L., Nyer, M., Cassano, P., Mischoulon, D., Alpert, J. E., et al. (2016) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.15m10056 · Cited by 126 · see citing works
Ketamine as a Potential Treatment for Suicidal Ideation: A Systematic Review of the Literature
Reinstatler, L., & Youssef, N. A. (2015) · Drugs in R&D · doi:10.1007/s40268-015-0081-0 · Cited by 120 · see citing works
New York State Psychiatric Institute
Shields, M. (2013) · Digital Commons @ Connecticut College (Connecticut College) · Cited by 113 · see citing works
Ketamine as a rapid-acting agent for suicidal ideation: A meta-analysis
Bartoli, F., Riboldi, I., Crocamo, C., Brita, C. D., Clerici, M., & Carrà, G. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.03.010 · Cited by 113 · see citing works
Suicidal ideation and the subjective aspects of depression
Keilp, J. G., Grunebaum, M. F., Gorlyn, M., LeBlanc, S., Burke, A. K., Galfalvy, H., Oquendo, M. A., & Mann, J. J. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.01.045 · Cited by 102 · see citing works
Self-citationSymptom components of standard depression scales and past suicidal behavior
Grunebaum, M. F., Keilp, J. G., Li, S., Ellis, S. P., Burke, A. K., Oquendo, M. A., & Mann, J. J. (2005) · Journal of Affective Disorders · doi:10.1016/j.jad.2005.03.002 · Cited by 67 · see citing works
Self-citationMilak, M. S., Rashid, R., Dong, Z., Kegeles, L. S., Grunebaum, M. F., Ogden, R. T., Lin, X., Mulhern, S. T., Suckow, R. F., Cooper, T. B., et al. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.13211 · Cited by 63 · see citing works
Self-citationCharacterizing the course of suicidal ideation response to ketamine
Ballard, E. D., Yarrington, J. S., Farmer, C., Richards, E. M., Machado‐Vieira, R., Kadriu, B., Niciu, M. J., Yuan, P., Park, L., & Zarate, C. A. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.07.077 · Cited by 56 · see citing works
Ketamine and suicidal ideation in depression: Jumping the gun?
Rajkumar, R., Fam, J., Yeo, E. Y. M., & Dawe, G. S. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.05.003 · Cited by 43 · see citing works
Ketamine metabolite pilot study in a suicidal depression trial
Grunebaum, M. F., Galfalvy, H. C., Choo, T.-H., Parris, M. S., Burke, A. K., Suckow, R. F., Cooper, T. B., & Mann, J. J. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.08.005 · Cited by 41 · see citing works
Self-citationSuicidal ideation declines with improvement in the subjective symptoms of major depression
Keilp, J. G., Ellis, S. P., Gorlyn, M., Burke, A. K., Oquendo, M. A., Mann, J. J., & Grunebaum, M. F. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.09.018 · Cited by 37 · see citing works
Self-citationKeilp, J. G., Madden, S. P., Gorlyn, M., Burke, A. K., Oquendo, M. A., & Mann, J. J. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.08.034 · Cited by 36 · see citing works
Self-citationPsychopharmacological Agents and Suicide Risk Reduction: Ketamine and Other Approaches
Jurdi, R. K. A., Swann, A. C., & Mathew, S. J. (2015) · Current Psychiatry Reports · doi:10.1007/s11920-015-0614-9 · Cited by 30 · see citing works
Milak, M. S., Keilp, J., Parsey, R. V., Oquendo, M. A., Malone, K. M., & Mann, J. J. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2010.03.002 · Cited by 28 · see citing works
Self-citationKeilp, J., Madden, S. P., Marver, J. E., Frawley, A. E., Burke, A., Herzallah, M. M., Gluck, M., Mann, J., & Grunebaum, M. F. (2021) · Journal of Clinical Psychiatry · doi:10.4088/jcp.21m13921 · Cited by 25 · see citing works
Self-citationKetamine for Treatment of Suicidal Ideation and Reduction of Risk for Suicidal Behavior
Mallick, F., & McCullumsmith, C. B. (2016) · Current Psychiatry Reports · doi:10.1007/s11920-016-0680-7 · Cited by 22 · see citing works
Grunebaum, M. F., Keilp, J., Ellis, S., Sudol, K., Bauer, N., Burke, A., Oquendo, M., & Mann, J. (2013) · Journal of Clinical Psychiatry · doi:10.4088/jcp.12m08000 · Cited by 21 · see citing works
Self-citationClinical Handbook for the Management of Mood Disorders
Mann, J., McGrath, P. J., & Roose, S. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139175869 · Cited by 21 · see citing works
Self-citationSuicidal Wishes and Symptoms of Depression
Beck, A. T., Lester, D., & Albert, N. (1973) · Psychological Reports · doi:10.2466/pr0.1973.33.3.770 · Cited by 19 · see citing works
Opioid Receptor μ-1 and Ketamine Effects in a Suicidal Depression Trial
Grunebaum, M. F., Galfalvy, H., Liu, J., Huang, Y., Marcott, S., Burke, A. K., & Mann, J. J. (2020) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001237 · Cited by 11 · see citing works
Self-citationAntisuicidal Effects of Ketamine: A Promising First Step
Trivedi, M. H. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17111261 · Cited by 6 · see citing works
Ketamine and Suicidal Ideation
Glue, P., & Menkes, D. B. (2017) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000646 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- First MB, 1997. User's guide for the structured clinical interview for DSM-IV axis II personality disorders: SCID-II. American Psychiatric Press, Washington, DC.
- Schatzberg AF, DeBattista C, 2015. Manual of clinical psychopharmacology, Eighth edition. ed. American Psychiatric Publishing, a division of American Psychiatric Association, Washington, DC.
Cited by
Sorted by citations
Major depressive disorder: hypothesis, mechanism, prevention and treatment
Cui, L., Li, S., Wang, S., Wu, X., Liu, Y., Yu, W., Wang, Y., Tang, Y., Xia, M., & Li, B. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01738-y · Cited by 1,061 · see citing works
“481 In several studies, a single dose of ketamine reduced immobility in the forced swim test immediately after injection and had effects similar to those of an antidepressant.”
BackgroundKetamine and esketamine in suicidal thoughts and behaviors: a systematic review
Jollant, F., Colle, R., Nguyen, T. M. L., Corruble, E., Gardier, A. M., Walter, M., Abbar, M., & Wagner, G. (2023) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253231151327 · Cited by 56 · see citing works
- Authors
- Hochschild, A., Keilp, J. G., Madden, S. P., Burke, A. K., Mann, J. J., & Grunebaum, M. F.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Grunebaum, Michael F.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2022-03
- Volume
- 300
- Pages
- 10-16
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC8828686
- OpenAlex
- W4200454875
- Cited by
- 25
- References
- 61
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 4 · 2023: 4 · 2022: 2
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01 MH-096,784)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Keywords
- ketamine, midazolam, suicidal ideation, major depressive disorder, mood improvement, anxiety symptoms, rapid antidepressant effects
- MeSH terms
- Depression, Major Depressive Disorder, Humans, Ketamine, Midazolam, Suicidal Ideation
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
