Table 5.

Most relevant clinical studies reporting the antidepressant efficacy of ketamine on suicidality in patients with TRD.

Author(s), Year	Design	Sample Characteristics	Main Results	Limitations	Conclusions
DiazGranados et al. 2010b [46]	Open-label study	Thirty-three patients with TRD received a single open-label infusion of ketamine (0.5 mg/kg) and were rated at baseline and 40, 80, 120, and 230 minutes post-infusion with the SSI, MADRS, HDRS, and BDI.	Suicidal ideation scores decreased significantly after 40 minutes following ketamine infusion (MADRS and BDI suicide items: p <.001). This reduction remained significant through the first 4 hours post-infusion. Ten subjects (30%) had an SSI score ≥ 4 at baseline; all these scores dropped below 4 (9 dropped by 40 minutes and 1 by 80 minutes). Significant improvements at all time points have been found for depression, anxiety, and hopelessness.	The sample size was relatively small but the effect sizes were large. The open-label nature of the study may have biased the reported response. Whether ketamine may also reduce suicidal ideation in patients with a diagnosis other than TRD is unclear.	Suicidal ideation in TRD patients improved after 40 minutes of ketamine infusion and remained significantly improved for up to 4 hours post-infusion.
Price et al. 2009 [45]	Open-label study	Twenty-six patients with TRD were assessed using the suicidality item of the MADRS 2 hours before and 24 hours following a single subanesthetic dose of intravenous ketamine. Ten patients also completed the Implicit Association assessing implicit suicidal associations at comparable time points. In a second study, nine patients received twice-weekly ketamine infusions over a 12-day period.	MADRS scores were significantly reduced after 24 hours of a single infusion of ketamine and 81% of patients received a rating of 0 or 1 post-infusion. Specifically, of the 13 patients with clinically significant suicidal ideation at baseline, 62% reported a clinically significant improvement on suicidal ideation postinfusion. Implicit suicidal associations were also reduced following ketamine. MADRS reductions were sustained for 12 days by repeated-dose ketamine.	The sample size was relatively small. The sample of patients with TRD may be not representative of the entire population of depressed subjects.	Ketamine has rapid beneficial effects on suicidal cognition.
Larkin and Beautrais, 2011 [47]	Open-label study	Fourteen depressed emergency department patients with suicide ideation were treated with a single i.v. bolus of ketamine (0.2 mg/kg) over 1-2 minutes.	Mean MADRS scores reduced significantly from 40.4 at baseline to 11.5 at 240 minutes. Median time to MADRS score ≤10 was 80 minutes. Suicidal ideation according to the item 10 of MADRS decreased significantly from 3.9 at baseline to 0.6 after 40 min post-administration. Suicidal ideation improvements were reported for the course of 10 days after ketamine infusions.	The open-label and preliminary nature of the study did not allow the generalization of findings.	Intravenous ketamine may rapidly improve suicidal ideation in depressed emergency department patients.