Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam‐controlled randomized clinical trial. (28th April 2017)

• Record Type: Journal Article
• Authors: Grunebaum, Michael F.; Ellis, Steven P.; Keilp, John G.; Moitra, Vivek K.; Cooper, Thomas B.; Marver, Julia E.; Burke, Ainsley K.; Milak, Matthew S.; Sublette, M. Elizabeth; Oquendo, Maria A.; Mann, J. John
• Is Part Of: Bipolar disorders. Volume 19:Number 3(2017)
• Page Start: 176
• Page End: 183
• Publication Date: 2017-04-28
• Subjects: bipolar disorder -- depression -- ketamine -- midazolam -- suicidal ideation; Manic-depressive illness -- Periodicals; Depression, Mental -- Periodicals; 616.895
• DOI: 10.1111/bdi.12487
• Languages: English
• ISSNs: 1398-5647

Abstract

Abstract : Objectives: To 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. Methods: Sixteen 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. Results: Results 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). Conclusions: The 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.