title: Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  ClinicalTrials.gov identifier: NCT01582945.
authors.affiliation: Massachusetts General Hospital, Depression Clinical and Research Program, 1 Bowdoin Sq, 6th Floor, Boston, MA 02114. dionescu@partners.org.|Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Dawn F
authors.initials: DF
authors.lastname: Ionescu
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Michaela B
authors.initials: MB
authors.lastname: Swee
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.|Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston.
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Pavone
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Taylor
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston.|Department of Psychology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Akeju
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Baer
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Maren
authors.initials: M
authors.lastname: Nyer
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cassano
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mischoulon
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Alpert
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.affiliation: Department of Psychology, Harvard University, Cambridge, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Nock
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cusin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D061218:Depressive Disorder, Treatment-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011594:Psychometrics; D012074:Remission Induction; D059020:Suicidal Ideation; D055815:Young Adult
chemical_list: D007649:Ketamine