{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:25:39Z","timestamp":1790637939134,"version":"4.1.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-\u00c5sberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median\u2009=\u200955.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours;\n                    <jats:italic>\u03b2<\/jats:italic>\n                    *(95% CI)\u2009=\u20090.58 (0.44, 0.72);\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001] and post-acute [~7 days;\n                    <jats:italic>\u03b2<\/jats:italic>\n                    *(95% CI)\u2009=\u20090.38 (0.23, 0.54);\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (\u22652 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size\n                    <jats:italic>r<\/jats:italic>\n                    \u2009\u2264\u20090.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Review Registration:<\/jats:bold>\n                    PROSPERO Identifier: CRD42021235630\n                  <\/jats:p>","DOI":"10.1038\/s41380-022-01757-7","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T07:05:14Z","timestamp":1662534314000},"page":"5096-5112","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-4325","authenticated-orcid":false,"given":"Rebecca B.","family":"Price","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4521-7903","authenticated-orcid":false,"given":"Nicholas","family":"Kissel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Baumeister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Rohac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L.","family":"Woody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5304-0127","authenticated-orcid":false,"given":"Elizabeth D.","family":"Ballard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Carlos A.","family":"Zarate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-962X","authenticated-orcid":false,"given":"William","family":"Deakin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5783-6181","authenticated-orcid":false,"given":"Chadi G.","family":"Abdallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2931-310X","authenticated-orcid":false,"given":"Adriana","family":"Feder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis S.","family":"Charney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5940-3478","authenticated-orcid":false,"given":"Michael F.","family":"Grunebaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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CAZ is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2\u2009R,6\u2009R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2\u2009R,6\u2009R)-hydroxynorketamine and (2\u2009S,6\u2009S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. CGA has served as a consultant, speaker and\/or on advisory boards for Aptinyx, Genentech, Janssen, Psilocybin Labs, Lundbeck, Guidepoint, and FSV7, and as editor of <i>Chronic Stress<\/i> for Sage Publications, Inc. He also filed a patent for using mTORC1 inhibitors to augment the effects of antidepressants (Aug 20, 2018). AF is named co-inventor on an issued patent in the United States and several issued patents outside of the United States, filed by the Icahn School of Medicine at Mount Sinai (AF\u2019s employer) for the use of ketamine as therapy for posttraumatic stress disorder; this intellectual property has not been licensed. DSC is named as co-inventor on patents filed by the Icahn School of Medicine at Mount Sinai (ISMMS) relating to the treatment for treatment-resistant depression, suicidal ideation and other disorders. ISMMS has entered into a licensing agreement with Janssen Pharmaceuticals, Inc. and it has and will receive payments from Janssen under the license agreement related to these patents for the treatment of treatment-resistant depression and suicidal ideation. Consistent with the ISMMS Faculty Handbook (the medical school policy), DSC is entitled to a portion of the payments received by the ISMMS. Since SPRAVATO has received regulatory approval for treatment-resistant depression, ISMMS and thus, through the ISMMS, DSC, will be entitled to additional payments, beyond those already received, under the license agreement. DSC is a named co-inventor on several patents filed by ISMMS for a cognitive training intervention to treat depression and related psychiatric disorders. The ISMMS has entered into a licensing agreement with Click Therapeutics, Inc. and has and will receive payments related to the use of this cognitive training intervention for the treatment of psychiatric disorders. In accordance with the ISMMS Faculty Handbook, DSC has received a portion of these payments and is entitled to a portion of any additional payments that the medical school might receive from this license with Click Therapeutics. DSC is a named co-inventor on a patent application filed by the ISMMS for the use of intranasally administered Neuropeptide Y (NPY) for the treatment of mood and anxiety disorders. This intellectual property has not been licensed. DSC is a named co-inventor on a patent application in the US, and several issued patents outside the US filed by the ISMMS related to the use of ketamine for the treatment of post-traumatic stress disorder (PTSD). This intellectual property has not been licensed. DSC is a named co-inventor on a patent application filed by ISMMS for systems and methods for providing a resilience building application to support mental health of subjects. This intellectual property has not been licensed. In the past 5 years, JWM has provided consultation services and\/or served on advisory boards for Boehreinger Ingelheim, Clexio Biosciences, Engrail Therapeutics, FSV7, Global Medical Education (GME), Otsuka, and Sage Therapeutics. JWM is named on a patent pending for neuropeptide Y as a treatment for mood and anxiety disorders and on a patent pending for the use of KCNQ channel openers to treat depression and related conditions. The Icahn School of Medicine (employer of JWM) is named on a patent and has entered into a licensing agreement and will receive payments related to the use of ketamine or esketamine for the treatment of depression. The Icahn School of Medicine is also named on a patent related to the use of ketamine for the treatment of PTSD. JWM is not named on these patents and will not receive any payments. JJM receives royalties for commercial use of the C-SSRS from the Research Foundation for Mental Hygiene. SJM is supported through the use of resources and facilities at the Michael E. Debakey VA Medical Center, Houston, Texas and receives support from The Menninger Clinic, Houston, Texas. SJM has served as a consultant to Allergan, Alkermes, Axsome Therapeutics, BioXcel Therapeutics, Clexio Biosciences, Eleusis, EMA Wellness, Engrail Therapeutics, Greenwich Biosciences, Intra-Cellular Therapies, Janssen, Levo Therapeutics, Perception Neurosciences, Praxis Precision Medicines, Neumora, Neurocrine, Relmada Therapeutics, Sage Therapeutics, Seelos Therapeutics, Signant Health, and Worldwide Clinical Trials. SJM has served as an investigator for clinical trials funded by Janssen, Merck, NeuroRx, and Sage Therapeutics, and has received research support from Biohaven Pharmaceuticals and VistaGen Therapeutics. DMM has received speaker\u2019s honoraria from MECTA, Otsuka and Janssen and an honorarium from Janssen for participating in an esketamine advisory board meeting. GP has served as a consultant for Abbott Laboratories, Acadia Pharmaceuticals, Inc, Alkermes, Inc, Alphasigma USA, Inc, AstraZeneca PLC, Avanir Pharmaceuticals, Axsome Therapeutics, Boston Pharmaceuticals, Inc., Brainsway Ltd, Bristol-Myers Squibb Company, Cala Health, Cephalon Inc., Dey Pharma, L.P., Eleusis health solutions ltd, Eli Lilly Co., Genentech, Inc, Genomind, Inc, GlaxoSmithKline, Evotec AG, H. Lundbeck A\/S, Inflabloc Pharmaceuticals, Janssen Global Services LLC, Jazz Pharmaceuticals, Johnson & Johnson Companies, Methylation Sciences Inc, Monopteros Therapeutics, Mylan Inc, Novartis Pharma AG, One Carbon Therapeutics, Inc, Osmotica Pharmaceutical Corp., Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer Inc., Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sage Therapeutics, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Taisho Pharmaceutical Co, Ltd, Takeda Pharmaceutical Company LTD, Theracos, Inc., and Wyeth, Inc. GP has received honoraria (for lectures or consultancy) from Abbott Laboratories, Acadia Pharmaceuticals Inc, Alkermes Inc, Alphasigma USA Inc, Asopharma America Cntral Y Caribe, Astra Zeneca PLC, Avanir Pharmaceuticals, Bristol-Myers Squibb Company, Brainsway Ltd, Cephalon Inc., Dey Pharma, L.P., Eli Lilly Co., Evotec AG, Forest Pharmaceuticals, GlaxoSmithKline, Inflabloc Pharmaceuticals, Grunbiotics Pty LTD, Hypera S.A., Jazz Pharmaceuticals, H. Lundbeck A\/S, Medichem Pharmaceuticals, Inc, Meiji Seika Pharma Co. Ltd, Novartis Pharma AG, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pharma Trade SAS, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company LTD, Theracos, Inc., Titan Pharmaceuticals, and Wyeth Inc. GP has received research support (paid to hospital) from Alphasigma USA, Inc, AstraZeneca PLC, Bristol-Myers Squibb Company, Cala Health, Forest Pharmaceuticals, the National Institute of Mental Health, Mylan Inc, Neuralstem, Inc, PAMLAB LLC, PCORI, Pfizer Inc., Johnson & Johnson Companies, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sunovion Pharmaceuticals, Tal Medical, and Theracos, Inc. GP has served (not currently) on the speaker\u2019s bureau for BristolMyersSquibb Co and Pfizer, Inc. STW has received contract funding from Janssen, Sage Therapeutics, and Oui Therapeutics for the conduct of clinical trials administered through Yale University; he has received consulting fees from Biohaven Pharmaceuticals, Sage Therapeutics, Janssen, and Oui Therapeutics. No other authors have conflicts of interest to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}