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Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam‐controlled randomized clinical trial
Author(s) -
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
Publication year - 2017
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12487
Subject(s) - ketamine , midazolam , neurocognitive , anesthesia , medicine , randomized controlled trial , depression (economics) , suicidal ideation , psychology , psychiatry , poison control , sedation , cognition , injury prevention , environmental health , economics , macroeconomics
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.