Department of Psychiatry, University of California Irvine, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Int J Neuropsychopharmacol. 2012 Jun;15(5):695-713. doi: 10.1017/S1461145711000927. Epub 2011 Jul 7.
Current antidepressants are ineffective in many depressed patients. Thus there is an urgent need to develop treatment strategies which have significantly faster response, can be sustained and have minimal side-effects. This paper reviews clinical data, potential biomarkers, mechanisms of action and future research directions for two proven strategies that produce marked improvement in severe depressive symptoms within 48 h, ketamine and sleep deprivation therapy (SDT). These treatments provide unequivocal evidence that the depressive process can be rapidly reversed in a subgroup of patients. Seventeen ketamine studies in over 150 patients showed a rapid response. Low-dose intravenous ketamine produced mild psychotomimetic effects but response has not been effectively sustained. SDT has been investigated in over 60 studies with a 40-60% response rate within 48 h. Although SDT is often used in Europe to initiate a rapid response, it is less utilized within the USA, in part, because it has a short duration when administered alone. We review data concerning chronotherapeutic strategies of bright-light therapy (BLT) and sleep-phase advance (SPA) which successfully sustain the antidepressant efficacy of SDT. Evidence is further discussed that a significant group of mood disorders have abnormal circadian rhythms which are known to be controlled by clock genes. It is hypothesized that chronotherapeutic manipulations can reset clock genes and thus, abnormalities in circadian rhythms. Further findings are reviewed that ketamine, in addition to its role as an NMDA antagonist, can also alter circadian rhythms. Thus, ketamine may share a critical mechanism with SDT.
目前的抗抑郁药物在许多抑郁症患者中无效。因此，迫切需要开发治疗策略，这些策略具有更快的反应速度、可持续性和最小的副作用。本文综述了两种已被证实的策略的临床数据、潜在生物标志物、作用机制和未来研究方向，这两种策略可在 48 小时内显著改善重度抑郁症状。这些治疗方法提供了明确的证据，表明在一小部分患者中，抑郁过程可以迅速逆转。17 项关于 150 多名患者的氯胺酮研究表明，氯胺酮治疗有迅速的反应。低剂量静脉内氯胺酮产生轻微的精神病样效应，但反应并未得到有效维持。睡眠剥夺疗法（SDT）已在 60 多项研究中进行了研究，在 48 小时内的反应率为 40-60%。尽管 SDT 通常在欧洲用于快速起效，但在美国的应用较少，部分原因是单独使用时持续时间较短。我们回顾了关于光疗法（BLT）和睡眠时相提前（SPA）的时间治疗策略的数据，这些策略成功地维持了 SDT 的抗抑郁疗效。进一步讨论了证据表明，一组显著的心境障碍存在异常的昼夜节律，这些节律已知由时钟基因控制。假设时间治疗可以重置时钟基因，从而纠正昼夜节律异常。还回顾了氯胺酮的进一步发现，除了作为 NMDA 拮抗剂的作用外，还可以改变昼夜节律。因此，氯胺酮可能与 SDT 有共同的关键机制。
