Samuel T Wilkinson1, Elizabeth D Ballard1, Michael H Bloch1, Sanjay J Mathew1, James W Murrough1, Adriana Feder1, Peter Sos1, Gang Wang1, Carlos A Zarate1, Gerard Sanacora1. 1. From the Department of Psychiatry and the Child Study Center, Yale School of Medicine, New Haven, Conn.; the Experimental Therapeutics and Pathophysiology Branch, NIMH, Bethesda, Md.; the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston; the Michael E. Debakey VA Medical Center, Houston; the Mood and Anxiety Disorders Program, Icahn School of Medicine at Mount Sinai, New York; the Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic; and the Beijing Anding Hospital, Capital University of Medical Sciences, Beijing.
Abstract
OBJECTIVE: Suicide is a public health crisis with limited treatment options. The authors conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation. METHOD: Individual participant data were obtained from 10 of 11 identified comparison intervention studies that used either saline or midazolam as a control treatment. The analysis included only participants who had suicidal ideation at baseline (N=167). A one-stage, individual participant data, meta-analytic procedure was employed using a mixed-effects, multilevel, general linear model. The primary outcome measures were the suicide items from clinician-administered (the Montgomery-Åsberg Depression Rating Scale [MADRS] or the Hamilton Depression Rating Scale [HAM-D]) and self-report scales (the Quick Inventory of Depressive Symptomatology-Self Report [QIDS-SR] or the Beck Depression Inventory [BDI]), obtained for up to 1 week after ketamine administration. RESULTS: Ketamine rapidly (within 1 day) reduced suicidal ideation significantly on both the clinician-administered and self-report outcome measures. Effect sizes were moderate to large (Cohen's d=0.48-0.85) at all time points after dosing. A sensitivity analysis demonstrated that compared with control treatments, ketamine had significant benefits on the individual suicide items of the MADRS, the HAM-D, and the QIDS-SR but not the BDI. Ketamine's effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms. CONCLUSIONS: Ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation. Ketamine's effects on suicidal ideation were partially independent of its effects on mood, although subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation. Additional research on ketamine's long-term safety and its efficacy in reducing suicide risk is needed before clinical implementation.
OBJECTIVE: Suicide is a public health crisis with limited treatment options. The authors conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation. METHOD: Individual participant data were obtained from 10 of 11 identified comparison intervention studies that used either saline or midazolam as a control treatment. The analysis included only participants who had suicidal ideation at baseline (N=167). A one-stage, individual participant data, meta-analytic procedure was employed using a mixed-effects, multilevel, general linear model. The primary outcome measures were the suicide items from clinician-administered (the Montgomery-Åsberg Depression Rating Scale [MADRS] or the Hamilton Depression Rating Scale [HAM-D]) and self-report scales (the Quick Inventory of Depressive Symptomatology-Self Report [QIDS-SR] or the Beck Depression Inventory [BDI]), obtained for up to 1 week after ketamine administration. RESULTS:Ketamine rapidly (within 1 day) reduced suicidal ideation significantly on both the clinician-administered and self-report outcome measures. Effect sizes were moderate to large (Cohen's d=0.48-0.85) at all time points after dosing. A sensitivity analysis demonstrated that compared with control treatments, ketamine had significant benefits on the individual suicide items of the MADRS, the HAM-D, and the QIDS-SR but not the BDI. Ketamine's effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms. CONCLUSIONS:Ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressedpatients with suicidal ideation. Ketamine's effects on suicidal ideation were partially independent of its effects on mood, although subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation. Additional research on ketamine's long-term safety and its efficacy in reducing suicide risk is needed before clinical implementation.
Authors: Charles H Kellner; Max Fink; Rebecca Knapp; Georgios Petrides; Mustafa Husain; Teresa Rummans; Martina Mueller; Hilary Bernstein; Keith Rasmussen; Kevin O'connor; Glenn Smith; A John Rush; Melanie Biggs; Shawn McClintock; Samuel Bailine; Chitra Malur Journal: Am J Psychiatry Date: 2005-05 Impact factor: 18.112
Authors: Gregory K Brown; Thomas Ten Have; Gregg R Henriques; Sharon X Xie; Judd E Hollander; Aaron T Beck Journal: JAMA Date: 2005-08-03 Impact factor: 56.272
Authors: Adriana Feder; Michael K Parides; James W Murrough; Andrew M Perez; Julia E Morgan; Shireen Saxena; Katherine Kirkwood; Marije Aan Het Rot; Kyle A B Lapidus; Le-Ben Wan; Dan Iosifescu; Dennis S Charney Journal: JAMA Psychiatry Date: 2014-06 Impact factor: 21.596
Authors: J W Murrough; L Soleimani; K E DeWilde; K A Collins; K A Lapidus; B M Iacoviello; M Lener; M Kautz; J Kim; J B Stern; R B Price; A M Perez; J W Brallier; G J Rodriguez; W K Goodman; D V Iosifescu; D S Charney Journal: Psychol Med Date: 2015-08-12 Impact factor: 7.723
Authors: Rebecca B Price; Dan V Iosifescu; James W Murrough; Lee C Chang; Rayan K Al Jurdi; Syed Z Iqbal; Laili Soleimani; Dennis S Charney; Alexandra L Foulkes; Sanjay J Mathew Journal: Depress Anxiety Date: 2014-03-25 Impact factor: 6.505
Authors: Gerard Sanacora; Mark A Frye; William McDonald; Sanjay J Mathew; Mason S Turner; Alan F Schatzberg; Paul Summergrad; Charles B Nemeroff Journal: JAMA Psychiatry Date: 2017-04-01 Impact factor: 21.596
Authors: Chadi G Abdallah; Lynnette A Averill; Teddy J Akiki; Mohsin Raza; Christopher L Averill; Hassaan Gomaa; Archana Adikey; John H Krystal Journal: Annu Rev Pharmacol Toxicol Date: 2018-09-14 Impact factor: 13.820
Authors: Jessica R Gilbert; Elizabeth D Ballard; Christina S Galiano; Allison C Nugent; Carlos A Zarate Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2019-12-03
Authors: Elizabeth D Ballard; Julia S Yarrington; Cristan A Farmer; Erica Richards; Rodrigo Machado-Vieira; Bashkim Kadriu; Mark J Niciu; Peixiong Yuan; Lawrence Park; Carlos A Zarate Journal: J Affect Disord Date: 2018-07-30 Impact factor: 4.839
Authors: Jennifer B Dwyer; Argyris Stringaris; David A Brent; Michael H Bloch Journal: J Child Psychol Psychiatry Date: 2020-02-04 Impact factor: 8.982