Lai Rosalyn, Katalinic Natalie, Glue Paul, Somogyi Andrew A, Mitchell Philip B, Leyden John, Harper Simon, Loo Colleen K
South Eastern Sydney Local Health District and University of New South Wales , Sydney.
World J Biol Psychiatry. 2014 Sep;15(7):579-84. doi: 10.3109/15622975.2014.922697. Epub 2014 Jun 9.
Research studies have reported impressive antidepressant effects with ketamine but significant knowledge gaps remain over the best method of administering ketamine, and the relationships between dose, antidepressant response and adverse effects.
In this pilot dose-finding study, the efficacy and tolerability of ketamine given by rapid intravenous (i.v.) infusion were assessed in a double-blind, placebo-controlled, crossover design, in four subjects with treatment- resistant depression. Each subject received up to four i.v. doses of ketamine (0.1, 0.2, 0.3, 0.4 mg/kg), given over 2-5 min, 1 week apart, and one randomly inserted placebo treatment.
Three of four subjects achieved antidepressant response (≥ 50% decrease in Montgomery-Asberg Depression Rating Scale scores), two at the minimum 0.1 mg/kg dose, though all relapsed within a week. For two subjects, the greatest improvement occurred at the highest dose received. Rapid infusion over 2 min led to significant adverse psychotomimetic effects which also increased proportionately with ketamine dosage.
This is the first trial to present dose-response data of ketamine efficacy and psychomimetic effects in depressed subjects. Antidepressant efficacy may be dose-related. Psychotomimetic effects were dose-related. Rapid infusion over 2 min may not be a feasible clinical approach to treatment, given poor tolerability.
研究报告称氯胺酮具有显著的抗抑郁作用，但在氯胺酮的最佳给药方法以及剂量、抗抑郁反应和不良反应之间的关系方面，仍存在重大知识空白。
在这项初步剂量探索研究中，采用双盲、安慰剂对照、交叉设计，对4名难治性抑郁症患者评估了快速静脉输注氯胺酮的疗效和耐受性。每位受试者接受高达4次静脉注射氯胺酮（0.1、0.2、0.3、0.4mg/kg），在2 - 5分钟内给药，间隔1周，以及1次随机插入的安慰剂治疗。
4名受试者中有3名出现抗抑郁反应（蒙哥马利 - 阿斯伯格抑郁评定量表评分降低≥50%），2名在最低0.1mg/kg剂量时出现反应，不过所有患者在1周内均复发。对于2名受试者，最大改善出现在所接受的最高剂量时。2分钟内快速输注导致显著的拟精神病性不良反应，且这些反应也随氯胺酮剂量成比例增加。
这是第一项呈现氯胺酮在抑郁症患者中疗效和拟精神病性效应剂量反应数据的试验。抗抑郁疗效可能与剂量相关。拟精神病性效应与剂量相关。鉴于耐受性差，2分钟内快速输注可能不是一种可行的临床治疗方法。
