Rapid Resolution of Suicidal Ideation After a Single Infusion of an N-Methyl-d-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder

Objective: Suicidal ideation is a medical emergency, especially when severe. Little research has been done on pharmacologic interventions that could address this problem. Ketamine, an N-methyl-d-aspartate antagonist, has been reported to have antidepressant effects within hours. We examined the effects of a single dose of ketamine on suicidal ideation in subjects with treatment-resistant major depressive disorder (MDD).

Method: Thirty-three subjects with DSM-IV-diagnosed MDD received a single open-label infusion of ketamine (0.5 mg/kg) and were rated at baseline and at 40, 80, 120, and 230 minutes postinfusion with the Scale for Suicide Ideation (SSI), the Montgomery-Åsberg Depression Rating Scale, the Hamilton Depression Rating Scale, and the Beck Depression Inventory. The study was conducted between October 2006 and January 2009.

Results: Suicidal ideation scores decreased significantly on the SSI as well as on the suicide subscales of other rating instruments within 40 minutes; these decreases remained significant through the first 4 hours postinfusion (P < .001). 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). For those patients with a starting score below 4 on the SSI, only 1 reached a score of 4. Depression, anxiety, and hopelessness were significantly improved at all time points (P < .001).

Conclusions: Suicidal ideation in the context of MDD improved within 40 minutes of a ketamine infusion and remained improved for up to 4 hours postinfusion. Future studies with ketamine in suicidal ideation are warranted due to the potential impact on public health.

Trial Registration: clinicaltrials.gov Identifier: NCT00088699

J Clin Psychiatry

Submitted: May 4, 2009; accepted July 14, 2009.

Online ahead of print: July 13, 2010 (doi:10.4088/JCP.09m05327blu).

Corresponding author: Carlos A. Zarate Jr, MD, 10 Center Drive, CRC, 7 Southeast Unit, Room 7-3465, Bethesda, MD 20892 ([email protected]).