Bauer Michael, Adli Mazda, Baethge Christopher, Berghöfer Anne, Sasse Johanna, Heinz Andreas, Bschor Tom
Department of Psychiatry and Psychotherapy, Charité University Hospital, Humboldt-University at Berlin, Schumannstr. 20/21, 10117 Berlin, Germany.
Can J Psychiatry. 2003 Aug;48(7):440-8. doi: 10.1177/070674370304800703.
This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research.
We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin.
Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% (P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways.
Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.
本系统评价旨在审查相关证据，并讨论锂盐增效作为难治性重度抑郁发作治疗策略的临床相关性。它还探讨了锂盐增效作用机制的假说，重点关注血清素（5-HT）和神经内分泌系统，并提出未来研究的建议。
我们检索了Medline计算机数据库和Cochrane图书馆，以查找1966年1月至2003年2月期间发表的英文相关原始研究。关键词如下：锂盐、增效策略、锂盐增效、重度抑郁症、难治性抑郁症、抗治疗性抑郁症、神经内分泌学和血清素。
自1981年以来发表的27项前瞻性临床研究中，10项为双盲、安慰剂对照试验，4项为随机对照试验，13项为开放标签试验。9项急性期安慰剂对照试验中有5项表明锂盐增效具有显著疗效。在急性治疗试验中，锂盐组的平均缓解率为45%，安慰剂组为18%（P<0.001）。一项安慰剂对照试验显示锂盐增效在维持期治疗中有疗效。综合开放和对照数据，约50%的患者在2至6周内对锂盐增效有反应。动物研究提供了有力证据，表明锂盐增效可能通过锂盐与抗抑郁药对脑5-HT通路的协同作用增加5-HT神经传递。
在难治性抑郁症的治疗中，锂盐联合抗抑郁药是记录最充分的增效治疗方法。动物研究新出现的数据表明，5-HT能系统参与了锂盐的增效作用。
