The rapid anti-suicidal ideation effect of ketamine: A systematic review

Prev Med. 2021 Nov;152(Pt 1):106524. doi: 10.1016/j.ypmed.2021.106524. Epub 2021 Sep 16.


In many countries suicide rates have been trending upwards for close to twenty years-presenting a public health crisis. Most suicide attempts and deaths are associated with psychiatric illness, usually a depressive disorder. Subanesthetic ketamine is the only FDA-approved antidepressant that works in hours not weeks-thus potentially transforming treatment of suicidal patients. We reviewed all randomized controlled trials of the effect of ketamine on suicidal ideation to determine if ketamine rapidly reduces suicidal ideation [SI] in depressed patients and how long the benefit persists after one dose and if the route of administration or dose affects the outcome. A systematic review was conducted as per PRISMA [preferred reporting items for systematic reviews and meta-analyses] criteria. PubMed search inclusive of "ketamine" and "suicide" yielded 358 results. Papers (N = 354) were then read by at least two authors, identifying 12 meeting eligibility requirements and eleven RCTs examining whether ketamine treatment ameliorated SI. Four of five RCTs examined racemic ketamine (0.5 mg/kg) given intravenously and found an advantage for ketamine over control for rapid reduction in SI in acutely depressed patients. Two studies examined intranasal esketamine in depressed suicidal patients and found no advantage over saline. One study examined outcome six weeks after a single intravenous dose of ketamine and found benefit for SI sustained relative to 24 h post-dose. Further research is warranted into: optimal dosing strategy, including number and frequency; and long-term efficacy and safety. Ultimately, it remains to be shown that ketamine's benefit for SI translates into prevention of suicidal behavior.

Keywords: Bipolar; Depression; Depressive disorder; Glutamate; Ketamine; Suicidal ideation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Depressive Disorder, Major*
  • Humans
  • Ketamine* / therapeutic use
  • Suicidal Ideation
  • Suicide, Attempted


  • Antidepressive Agents
  • Ketamine