PMID- 28452409
OWN - NLM
STAT- MEDLINE
DCOM- 20180222
LR  - 20220331
IS  - 1399-5618 (Electronic)
IS  - 1398-5647 (Linking)
VI  - 19
IP  - 3
DP  - 2017 May
TI  - Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot 
      midazolam-controlled randomized clinical trial.
PG  - 176-183
LID - 10.1111/bdi.12487 [doi]
AB  - 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 
      (rho=-.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, rho=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.
CI  - (c) 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Grunebaum, Michael F
AU  - Grunebaum MF
AUID- ORCID: 0000-0001-5940-3478
AD  - Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia 
      University Medical Center (CUMC) and New York State Psychiatric Institute, New 
      York, NY, USA.
FAU - Ellis, Steven P
AU  - Ellis SP
AD  - Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia 
      University Medical Center (CUMC) and New York State Psychiatric Institute, New 
      York, NY, USA.
FAU - Keilp, John G
AU  - Keilp JG
AD  - Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia 
      University Medical Center (CUMC) and New York State Psychiatric Institute, New 
      York, NY, USA.
FAU - Moitra, Vivek K
AU  - Moitra VK
AD  - Department of Anesthesiology, CUMC, New York, NY, USA.
FAU - Cooper, Thomas B
AU  - Cooper TB
AD  - Analytical Psychopharmacology Laboratory, Nathan Kline Institute, Research 
      Foundation for Mental Hygiene of New York State, Orangeburg, NY, USA.
FAU - Marver, Julia E
AU  - Marver JE
AD  - Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia 
      University Medical Center (CUMC) and New York State Psychiatric Institute, New 
      York, NY, USA.
FAU - Burke, Ainsley K
AU  - Burke AK
AD  - Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia 
      University Medical Center (CUMC) and New York State Psychiatric Institute, New 
      York, NY, USA.
FAU - Milak, Matthew S
AU  - Milak MS
AD  - Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia 
      University Medical Center (CUMC) and New York State Psychiatric Institute, New 
      York, NY, USA.
FAU - Sublette, M Elizabeth
AU  - Sublette ME
AD  - Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia 
      University Medical Center (CUMC) and New York State Psychiatric Institute, New 
      York, NY, USA.
FAU - Oquendo, Maria A
AU  - Oquendo MA
AD  - Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 
      USA.
FAU - Mann, J John
AU  - Mann JJ
AD  - Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia 
      University Medical Center (CUMC) and New York State Psychiatric Institute, New 
      York, NY, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170428
PL  - Denmark
TA  - Bipolar Disord
JT  - Bipolar disorders
JID - 100883596
RN  - 0 (Anesthetics, Dissociative)
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (GABA Modulators)
RN  - 690G0D6V8H (Ketamine)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - R60L0SM5BC (Midazolam)
SB  - IM
MH  - Adult
MH  - Anesthetics, Dissociative/administration & dosage/adverse effects
MH  - Biomarkers/analysis
MH  - *Bipolar Disorder/diagnosis/drug therapy/psychology
MH  - Brain-Derived Neurotrophic Factor/analysis
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Monitoring/methods
MH  - Female
MH  - GABA Modulators/administration & dosage/adverse effects
MH  - Humans
MH  - *Ketamine/administration & dosage/adverse effects
MH  - Male
MH  - Memory/*drug effects
MH  - *Midazolam/administration & dosage/adverse effects
MH  - Middle Aged
MH  - *Suicidal Ideation
MH  - Treatment Outcome
OTO - NOTNLM
OT  - bipolar disorder
OT  - depression
OT  - ketamine
OT  - midazolam
OT  - suicidal ideation
EDAT- 2017/04/30 06:00
MHDA- 2018/02/23 06:00
CRDT- 2017/04/29 06:00
PHST- 2016/10/31 00:00 [received]
PHST- 2017/03/12 00:00 [accepted]
PHST- 2017/04/30 06:00 [pubmed]
PHST- 2018/02/23 06:00 [medline]
PHST- 2017/04/29 06:00 [entrez]
AID - 10.1111/bdi.12487 [doi]
PST - ppublish
SO  - Bipolar Disord. 2017 May;19(3):176-183. doi: 10.1111/bdi.12487. Epub 2017 Apr 28.