Diamond Peter R, Farmery Andrew D, Atkinson Stephanie, Haldar Jag, Williams Nicola, Cowen Phil J, Geddes John R, McShane Rupert
Oxford Health NHS Foundation Trust, Oxford, UK.
Nuffield Department of Anaesthetics, University of Oxford, Oxford, UK.
J Psychopharmacol. 2014 Jun;28(6):536-44. doi: 10.1177/0269881114527361. Epub 2014 Apr 3.
Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medication on response rate and duration are not known.
Twenty-eight patients with uni- or bipolar TRD were treated over three weeks with either three or six ketamine infusions (0.5 mg/kg over 40 minutes) in the recovery room of a routine ECT clinic. Post-treatment memory assessments were conducted on day 21 (4-7 days after the final infusion). Patients were followed up for six months where possible, with severity of depression and side effects monitored throughout.
Eight (29%) patients responded of whom four remitted. Only three (11%) patients had responded within six hours after a single infusion, but in all responders, the response had developed before the third infusion. The duration of response from the final infusion was variable (median 70, range 25-168 days). Discontinuations included two (7%) because of acute adverse reactions during the infusion and five (18%) because of failure to benefit and increasing anxiety. Ketamine was not associated with memory impairment. The ECT clinic was rated suitable by patients and offered appropriate levels of monitoring.
This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop.
氯胺酮对难治性抑郁症（TRD）有快速抗抑郁作用。多次氯胺酮输注以及联合使用抗抑郁药物对认知功能、反应率和持续时间的影响尚不清楚。
28例单相或双相TRD患者在一家常规ECT诊所的恢复室接受为期三周的治疗，分别接受三次或六次氯胺酮输注（0.5mg/kg，40分钟内输注完毕）。在第21天（最后一次输注后4 - 7天）进行治疗后记忆评估。尽可能对患者进行为期六个月的随访，全程监测抑郁严重程度和副作用。
8例（29%）患者有反应，其中4例缓解。仅3例（11%）患者在单次输注后6小时内有反应，但所有有反应的患者在第三次输注前就已出现反应。最后一次输注后的反应持续时间各不相同（中位数70天，范围25 - 168天）。停药原因包括2例（7%）因输注期间出现急性不良反应，5例（18%）因未获益且焦虑加重。氯胺酮与记忆损害无关。患者对ECT诊所评价良好，其监测水平适宜。
这项小型、开放标签的观察性研究表明，在现有的英国国家医疗服务体系（NHS）临床结构中，对于正在服用抗抑郁药物的患者，最多可安全给予六次低剂量氯胺酮输注。反应率与在未服用抗抑郁药物的患者中进行的单剂量氯胺酮随机对照试验（RCT）相当，但反应出现时间稍长。
