Literature DB >> 27232360

Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study.

Dawn F Ionescu1,2,3, Michaela B Swee2, Kara J Pavone2,4, Norman Taylor4,3, Oluwaseun Akeju4,5, Lee Baer2,3, Maren Nyer2,3, Paolo Cassano2,3, David Mischoulon2,3, Jonathan E Alpert2,3, Emery N Brown4,3, Matthew K Nock5,3, Maurizio Fava2,3, Cristina Cusin2,3.   

Abstract

BACKGROUND: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown.
METHODS: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥ 3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS₂₈-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up.
RESULTS: Over the course of the infusions (acute treatment phase), 7 of 14 patients (50%) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P < .001), which approached significance even after controlling for severity of 6-item Hamilton Depression Rating Scale (HDRS₆) core depression items (P = .05). Similarly, there were significant decreases in the C-SSRS Intensity (P < .01) and HDRS₂₈-SI (P < .001) scores during the acute treatment phase. Two of the 7 patients who achieved remission during the acute treatment phase (29%) maintained their remission throughout a 3-month naturalistic follow-up.
CONCLUSIONS: In this preliminary study, repeated doses of open-label ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01582945. © Copyright 2016 Physicians Postgraduate Press, Inc.

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Year:  2016        PMID: 27232360     DOI: 10.4088/JCP.15m10056

Source DB:  PubMed          Journal:  J Clin Psychiatry        ISSN: 0160-6689            Impact factor:   4.384


  32 in total

Review 1.  Neuropathology of suicide: recent findings and future directions.

Authors:  P-E Lutz; N Mechawar; G Turecki
Journal:  Mol Psychiatry       Date:  2017-07-11       Impact factor: 15.992

2.  Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.

Authors:  Nolan R Williams; Boris D Heifets; Brandon S Bentzley; Christine Blasey; Keith D Sudheimer; Jessica Hawkins; David M Lyons; Alan F Schatzberg
Journal:  Mol Psychiatry       Date:  2019-08-29       Impact factor: 15.992

3.  Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial.

Authors:  Michael F Grunebaum; Hanga C Galfalvy; Tse-Hwei Choo; John G Keilp; Vivek K Moitra; Michelle S Parris; Julia E Marver; Ainsley K Burke; Matthew S Milak; M Elizabeth Sublette; Maria A Oquendo; J John Mann
Journal:  Am J Psychiatry       Date:  2017-12-05       Impact factor: 18.112

Review 4.  Investigational drugs in recent clinical trials for treatment-resistant depression.

Authors:  Ricardo P Garay; Carlos A Zarate; Thomas Charpeaud; Leslie Citrome; Christoph U Correll; Ahcène Hameg; Pierre-Michel Llorca
Journal:  Expert Rev Neurother       Date:  2017-01-29       Impact factor: 4.618

5.  Modulation of DNA Methylation and Gene Expression in Rodent Cortical Neuroplasticity Pathways Exerts Rapid Antidepressant-Like Effects.

Authors:  Amanda J Sales; Izaque S Maciel; Angélica C D R Suavinha; Sâmia R L Joca
Journal:  Mol Neurobiol       Date:  2020-10-06       Impact factor: 5.590

Review 6.  Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant.

Authors:  Weili Zhu; Zengbo Ding; Yinan Zhang; Jie Shi; Kenji Hashimoto; Lin Lu
Journal:  Neurosci Bull       Date:  2016-11-22       Impact factor: 5.203

7.  Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine.

Authors:  Kenichi Fukumoto; Manoela V Fogaça; Rong-Jian Liu; Catharine Duman; Taro Kato; Xiao-Yuan Li; Ronald S Duman
Journal:  Proc Natl Acad Sci U S A       Date:  2018-12-17       Impact factor: 11.205

8.  Effects of N, N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression.

Authors:  Lindsay P Cameron; Charlie J Benson; Lee E Dunlap; David E Olson
Journal:  ACS Chem Neurosci       Date:  2018-04-24       Impact factor: 4.418

9.  Medial PFC AMPA receptor and BDNF signaling are required for the rapid and sustained antidepressant-like effects of 5-HT1A receptor stimulation.

Authors:  Kenichi Fukumoto; Manoela V Fogaça; Rong-Jian Liu; Catharine H Duman; Xiao-Yuan Li; Shigeyuki Chaki; Ronald S Duman
Journal:  Neuropsychopharmacology       Date:  2020-05-12       Impact factor: 7.853

Review 10.  The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis.

Authors:  Samuel T Wilkinson; Elizabeth D Ballard; Michael H Bloch; Sanjay J Mathew; James W Murrough; Adriana Feder; Peter Sos; Gang Wang; Carlos A Zarate; Gerard Sanacora
Journal:  Am J Psychiatry       Date:  2017-10-03       Impact factor: 18.112

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