title: Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder.
abstract: OBJECTIVE
  Insomnia and disrupted sleep are associated with increased risk of suicide. The N-methyl-d-aspartate antagonist ketamine has been associated with reduced suicidal thoughts, but the mechanism of action is unknown. This study sought to evaluate differences in nocturnal wakefulness in depressed individuals who did and did not have an antisuicidal response to ketamine.
  
  
  METHODS
  Thirty-four participants with baseline suicidal ideation diagnosed with either DSM-IV major depressive disorder (n = 23) or bipolar depression (n = 11) between 2006 and 2013 completed nighttime electroencephalography (EEG) the night before and the night after a single ketamine infusion (0.5 mg/kg over 40 minutes). Suicidal ideation was assessed at baseline and the morning after ketamine infusion via several measures, including the Hamilton Depression Rating Scale suicide item, the suicide item of the Montgomery-Asberg Depression Rating Scale, and the first 5 items of the Scale for Suicide Ideation. A generalized linear mixed model evaluated differences in nocturnal wakefulness, as verified by EEG, between those who had an antisuicidal response to ketamine and those who did not, controlling for baseline nocturnal wakefulness. Results were also compared to the sleep of healthy controls (n = 22).
  
  
  RESULTS
  After analyses adjusted for baseline sleep, participants with an antisuicidal response to ketamine showed significantly reduced nocturnal wakefulness the night after ketamine infusion compared to those without an antisuicidal response (F₁,₂₂ = 5.04, P = .04). Level of nocturnal wakefulness after antisuicidal response to ketamine did not differ significantly from nocturnal wakefulness in the control sample but did differ at a trend level (F₁,₄₀ = 3.15, P = .08).
  
  
  CONCLUSIONS
  Reductions in wakefulness following ketamine may point to a biological mechanism underlying the effect of ketamine on suicidal ideation.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00088699.
authors.affiliation: Mayo Clinic, 200 First St SW, Rochester, MN 55902. vandevoort.jennifer@mayo.edu.|Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.|Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Vande Voort
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Ballard
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Bernert
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Richards
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Park
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Wallace C
authors.initials: WC
authors.lastname: Duncan
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D001714:Bipolar Disorder / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D003865:Major Depressive Disorder / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D016903:Drug Monitoring / Q000379:methods; D004351:Drug Resistance; D004569:Electroencephalography / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D059020:Suicidal Ideation; D013405:Suicide / Q000523:psychology; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects*; D000092864:Suicide Prevention
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine