Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial

Psychol Med. 2015 Dec;45(16):3571-80. doi: 10.1017/S0033291715001506. Epub 2015 Aug 12.

Abstract

Background: Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression.

Method: We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point.

Results: The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period.

Conclusions: The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.

Keywords: Depression; glutamate; ketamine; suicide; treatment.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Bipolar Disorder / epidemiology
  • Depression / drug therapy*
  • Depressive Disorder, Major / epidemiology
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists / administration & dosage*
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Female
  • Humans
  • Ketamine / administration & dosage*
  • Ketamine / therapeutic use
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Stress Disorders, Post-Traumatic / epidemiology
  • Suicidal Ideation*
  • Treatment Outcome

Substances

  • Excitatory Amino Acid Antagonists
  • Ketamine