Abou-Saleh Mohammed T, Müller-Oerlinghausen Bruno, Coppen Alec J
St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
Drug Commission of the German Medical Association, Freie Universität Berlin, Charité Universitäts-Medizin, Berlin, Germany.
Int J Bipolar Disord. 2017 Dec;5(1):11. doi: 10.1186/s40345-017-0080-x. Epub 2017 May 8.
Depressive disorders are a leading cause of the global burden of disease and are associated with high recurrent often continuing morbidity and high excess mortality by suicide and cardiovascular disease. Whilst there are established, effective and cost-effective treatments for depression, their long-term management is often neglected: there is continuing controversy over the case of need for long-term treatment including lifelong treatment and safety issues.
In this narrative review, we critically examine the evidence for the effectiveness and safety of lithium salts in the long-term management of unipolar depression. We refer to existing recent international guidelines as well as the scientific literature selectively and against the background of our longstanding experience with patients suffering from unipolar depression who are often under treated or inappropriately treated.
According to many studies mostly dating back to the 1970/1980s, lithium is efficacious in the prophylaxis of unipolar depression particularly depression with melancholia and delusional depression and showing a clearly episodic course. Also the efficacy of lithium maintenance treatment following recovery by ECT has been clearly shown. Moreover, convincing evidence exists that lithium has added value and benefit for its unique anti-suicidal effects as well as reducing mortality by other causes. The anti-suicidal effect has been convincingly demonstrated in bipolar as well as in unipolar patients. Nevertheless its use in the management of patients with unipolar depression has not been properly recognized by a majority of textbooks and guidelines. Whilst it has been well considered as an effective treatment for depression that has not responded to antidepressants as an adjunct treatment, also called augmentation, it has been much less recommended for the prevention of recurrent episodes of unipolar depression. One of the reasons for this neglect is the blurring of the diagnosis "unipolar depression" by modern diagnostic tools. Lithium will hardly work in a patient with "unipolar depression spectrum disease".
We conclude that lithium is an effective prophylactic treatment for carefully selected patients with unipolar depression and is safe when prescribed in recommended doses/plasma lithium levels and with regular, careful monitoring. We propose that lithium prophylaxis can be indicated in patients with unipolar depression and that the occurrence of 2 episodes of depression within 5 years is a practical criterion for starting lithium prophylaxis particularly in severe depression with psychotic features and high suicidal risk. Furthermore, an indication might be considered especially in unipolar patients in whom a bipolar background is suspected. In some cases, lithium prophylaxis may be recommended after a single episode of depression that is severe with high suicidal risk and continued life-long.
抑郁症是全球疾病负担的主要原因之一，与高复发率相关，常常持续发病，且因自杀和心血管疾病导致的额外死亡率很高。虽然有成熟、有效且具有成本效益的抑郁症治疗方法，但其长期管理往往被忽视：对于长期治疗（包括终身治疗）的必要性以及安全性问题仍存在持续的争议。
在本叙述性综述中，我们严格审查锂盐在单相抑郁症长期管理中的有效性和安全性证据。我们有选择地参考近期的国际指南以及科学文献，并结合我们长期以来对单相抑郁症患者的经验，这些患者常常治疗不足或治疗不当。
根据许多大多可追溯到20世纪70年代/80年代的研究，锂盐在预防单相抑郁症方面有效，尤其是伴有忧郁症和妄想性抑郁症且病程明显呈发作性的抑郁症。电休克治疗恢复后锂盐维持治疗的疗效也已得到明确证实。此外，有令人信服的证据表明，锂盐因其独特的抗自杀作用以及降低其他原因导致的死亡率而具有附加价值和益处。抗自杀作用在双相情感障碍患者以及单相抑郁症患者中均已得到令人信服的证明。然而，大多数教科书和指南并未正确认识到其在单相抑郁症患者管理中的应用。虽然它已被充分视为一种对未对抗抑郁药产生反应的抑郁症作为辅助治疗（也称为增效治疗）的有效方法，但对于预防单相抑郁症的复发发作，其推荐程度要低得多。这种忽视的原因之一是现代诊断工具使“单相抑郁症”的诊断变得模糊。锂盐对患有“单相抑郁症谱系疾病”的患者几乎无效。
我们得出结论，锂盐对于精心挑选的单相抑郁症患者是一种有效的预防性治疗方法，按照推荐剂量/血浆锂水平处方并进行定期、仔细监测时是安全的。我们建议，锂盐预防可用于单相抑郁症患者，5年内发生2次抑郁发作是开始锂盐预防的一个实用标准，特别是在伴有精神病性特征和高自杀风险的重度抑郁症患者中。此外，对于怀疑有双相情感障碍背景的单相患者，可能尤其应考虑给予该治疗指征。在某些情况下，对于单次发作且严重、有高自杀风险且需终身治疗的抑郁症患者，可能推荐锂盐预防。
