Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression

Biol Psychiatry. 2009 Sep 1;66(5):522-6. doi: 10.1016/j.biopsych.2009.04.029. Epub 2009 Jul 9.


Background: Intravenous ketamine has shown rapid antidepressant effects in early trials, making it a potentially attractive candidate for depressed patients at imminent risk of suicide. The Implicit Association Test (IAT), a performance-based measure of association between concepts, may have utility in suicide assessment.

Methods: Twenty-six patients with treatment-resistant depression were assessed using the suicidality item of the Montgomery-Asberg Depression Rating Scale (MADRS-SI) 2 hours before and 24 hours following a single subanesthetic dose of intravenous ketamine. Ten patients also completed IATs assessing implicit suicidal associations at comparable time points. In a second study, nine patients received thrice-weekly ketamine infusions over a 12-day period.

Results: Twenty-four hours after a single infusion, MADRS-SI scores were reduced on average by 2.08 points on a 0 to 6 scale (p < .001; d = 1.37), and 81% of patients received a rating of 0 or 1 postinfusion. Implicit suicidal associations were also reduced following ketamine (p = .003; d = 1.36), with reductions correlated across implicit and explicit measures. MADRS-SI reductions were sustained for 12 days by repeated-dose ketamine (p < .001; d = 2.42).

Conclusions: These preliminary findings support the premise that ketamine has rapid beneficial effects on suicidal cognition and warrants further study.

Trial registration: ClinicalTrials.gov NCT00419003 NCT00548964.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cohort Studies
  • Depression / drug therapy
  • Depression / psychology*
  • Drug Resistance
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Female
  • Humans
  • Infusions, Intravenous
  • Ketamine / administration & dosage
  • Ketamine / pharmacology*
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Suicide / psychology
  • Suicide Prevention*


  • Excitatory Amino Acid Antagonists
  • Ketamine

Associated data

  • ClinicalTrials.gov/NCT00419003
  • ClinicalTrials.gov/NCT00548964