• Michael F Grunebaum, Steven P Ellis, John G Keilp, Vivek K Moitra, Thomas B Cooper, Julia E Marver, Ainsley K Burke, Matthew S Milak, M Elizabeth Sublette, Maria A Oquendo, and J John Mann.
• Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia University Medical Center (CUMC) and New York State Psychiatric Institute, New York, NY, USA.
• Bipolar Disord. 2017 May 1; 19 (3): 176-183.

ObjectivesTo evaluate feasibility and effects of a sub-anesthetic infusion dose of ketamine versus midazolam on suicidal ideation in bipolar depression. Neurocognitive, blood and saliva biomarkers were explored.MethodsSixteen participants with bipolar depression and a Scale for Suicidal Ideation (SSI) score of ≥4 were randomized to ketamine (0.5 mg/kg) or midazolam (0.02 mg/kg). Current pharmacotherapy was maintained excluding benzodiazepines within 24 hours. The primary clinical outcome was SSI score on day 1 post-infusion.ResultsResults supported feasibility. Mean reduction of SSI after ketamine infusion was almost 6 points greater than after midazolam, although this was not statistically significant (estimate=5.84, SE=3.01, t=1.94, P=.074, 95% confidence interval ([CI)]=-0.65 to 12.31). The number needed to treat for response (SSI <4 and at least 50% below baseline) was 2.2, and for remission (SSI=0) was 3.2. The strongest neurocognitive correlation was between memory improvement on the Selective Reminding Test (SRT) and reduction in SSI score on day 1 after ketamine (ρ=-.89, P=.007). Pre- to post-infusion decrease in serum brain derived neurotrophic factor (BDNF) correlated with reduction in SSI from baseline to day 1 after ketamine (n=5, ρ=0.90, P=.037) but not midazolam (P=.087).ConclusionsThe study demonstrated feasibility. Suicidal thoughts were lower after ketamine than after midazolam at a trend level of significance, likely due to the small pilot sample. Memory improvement and BDNF are promising biomarkers. Replication is needed in an adequately powered full-scale trial.© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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