Citation

Grunebaum MF, Ellis SP, Keilp JG, Moitra VK, Cooper TB, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Bipolar Disord. 2017; 19(3): 176-183.

Copyright

(Copyright © 2017, John Wiley and Sons)

DOI

10.1111/bdi.12487

PMID

28452409

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.

Language: en

Keywords

Humans; Adult; Female; Male; Middle Aged; Treatment Outcome; Suicidal Ideation; Biomarkers; bipolar disorder; Double-Blind Method; ketamine; suicidal ideation; depression; Ketamine; Brain-Derived Neurotrophic Factor; Dose-Response Relationship, Drug; Bipolar Disorder; Memory; midazolam; Drug Monitoring; Midazolam; Anesthetics, Dissociative; GABA Modulators