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
Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia University Medical Center (CUMC) and New York State Psychiatric Institute, New York, NY, USA.
Department of Anesthesiology, CUMC, New York, NY, USA.
Bipolar Disord. 2017 May;19(3):176-183. doi: 10.1111/bdi.12487. Epub 2017 Apr 28.
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.
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 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).
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.
评估亚麻醉剂量的氯胺酮与咪达唑仑对双相抑郁患者自杀观念的可行性及效果。同时探究神经认知、血液及唾液生物标志物。
16例双相抑郁患者，自杀观念量表（SSI）评分≥4，被随机分为氯胺酮组（0.5mg/kg）或咪达唑仑组（0.02mg/kg）。维持当前药物治疗，但24小时内排除苯二氮䓬类药物。主要临床结局为输注后第1天的SSI评分。
结果支持该研究的可行性。氯胺酮输注后SSI的平均降低值比咪达唑仑输注后几乎高6分，尽管这无统计学意义（估计值=5.84，标准误=3.01，t=1.94，P=0.074，95%置信区间[CI]=-0.65至12.31）。达到反应（SSI<4且至少比基线低50%）所需治疗人数为2.2，达到缓解（SSI=0）所需治疗人数为3.2。最强的神经认知相关性存在于选择性提醒测试（SRT）中的记忆改善与氯胺酮输注后第1天SSI评分降低之间（ρ=-0.89，P=0.007）。氯胺酮输注前后血清脑源性神经营养因子（BDNF）的降低与SSI从基线到输注后第1天的降低相关（n=5，ρ=0.90，P=0.037），而与咪达唑仑无关（P=0.087）。
该研究证明了可行性。在具有趋势性显著水平上，氯胺酮治疗后自杀想法低于咪达唑仑治疗后，可能是由于样本量小。记忆改善和BDNF是有前景的生物标志物。需要在有足够样本量的全面试验中进行重复研究。
