Intervention Review

Lithium for maintenance treatment of mood disorders

  1. Sally SA Burgess2,
  2. John Geddes1,*,
  3. Keith KE Hawton3,
  4. Matthew J Taylor1,
  5. Ellen Townsend4,
  6. K Jamison5,
  7. Guy Goodwin1

Editorial Group: Cochrane Depression, Anxiety and Neurosis Group

Published Online: 23 JUL 2001

Assessed as up-to-date: 18 MAR 2001

DOI: 10.1002/14651858.CD003013


How to Cite

Burgess SSA, Geddes J, Hawton KKE, Taylor MJ, Townsend E, Jamison K, Goodwin G. Lithium for maintenance treatment of mood disorders. Cochrane Database of Systematic Reviews 2001, Issue 3. Art. No.: CD003013. DOI: 10.1002/14651858.CD003013.

Author Information

  1. 1

    University of Oxford, Department of Psychiatry, Oxford, UK

  2. 2

    Oxfordshire Mental Healthcare NHS Trust, Department of Psychiatry of Old Age, Oxford, UK

  3. 3

    Warneford Hospital, University Department of Psychiatry, Oxford, UK

  4. 4

    School of Psychology, University of Nottingham, Risk Analysis, Social Processes and Health Group, Nottingham, UK

  5. 5

    Oxford, UK

*John Geddes, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JK, UK. john.geddes@psych.ox.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 23 JUL 2001

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Mood disorders are common, disabling and tend to be recurrent. They carry a high risk of suicide. Maintenance treatment, aimed at the prevention of relapse, is therefore of vital importance. Lithium has been used for some years as the mainstay of maintenance treatment in bipolar affective disorder, and to a lesser extent in unipolar disorder. However, the efficacy and effectiveness of prophylactic lithium therapy has been disputed. Low suicide rates in lithium-treated patients have led to claims that lithium has a specific anti-suicidal effect. If so, this is of considerable importance as treatments for mental disorders in general have not been shown convincingly to be effective in suicide prevention.

Objectives

1. To investigate the efficacy of lithium treatment in the prevention of relapse in recurrent mood disorders.
2. To examine the effect of lithium treatment on consumers' general health and social functioning, its acceptability to consumers, and the side-effects of treatment.
3. To investigate the hypothesis that lithium has a specific effect in reducing the incidence of suicide and deliberate self-harm in persons with mood disorders.

Search methods

The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) and The Cochrane Controlled Clinical Trials Register (CCTR) were searched. Reference lists of relevant papers and major text books of mood disorder were examined. Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished. Specialist journals concerning lithium were hand searched.

Selection criteria

Randomised controlled trials comparing lithium with placebo, where the stated intent of treatment was maintenance or prophylaxis. Participants were males and females of all ages with diagnoses of mood disorder. Discontinuation studies (in which all participants had been stable on lithium for some time before being randomised to either continued lithium treatment or placebo substitution) were excluded.

Data collection and analysis

Data were extracted from the original reports independently by two reviewers. The main outcomes studied were related to the objectives stated above. Data were analysed for all diagnoses of mood disorder and for bipolar and unipolar disorder separately. Data were analysed using Review Manager version 4.0.

Main results

Nine studies were included in the review, reporting on 825 participants randomly allocated to lithium or placebo. Lithium was found to be more effective than placebo in preventing relapse in mood disorder overall, and in bipolar disorder. The most consistent effect was found in bipolar disorder (random effects OR 0.29; 95% CI 0.09 to 0.93 ). In unipolar disorder, the direction of effect was in favour of lithium, but the result (when heterogeneity between studies was allowed for) did not reach statistical significance. Considerable heterogeneity was found between studies in all groups of patients. The direction of effect was the same in all studies; no study found a negative effect for lithium. Heterogeneity may have been due to differences in selection of participants, and to differing exposures to lithium in the pre-study phase resulting in variable influence of a discontinuation effect. There was little reported data on overall health and social functioning of participants under the different treatment conditions, or on the participants' own views of their treatment. Descriptive analysis showed that assessments of general health and social functioning generally favoured lithium. Small absolute numbers of deaths and suicides, and the absence of data on non-fatal suicidal behaviours, made it impossible to draw meaningful conclusions about the place of lithium therapy in suicide prevention.

Authors' conclusions

This systematic review indicates that lithium is an efficacious maintenance treatment for bipolar disorder. In unipolar disorder the evidence of efficacy is less robust. This review does not cover the relative efficacy of lithium compared with other maintenance treatments, which is at present unclear. There is no definitive evidence from this review as to whether or not lithium has an anti-suicidal effect. Systematic reviews and large scale randomised studies comparing lithium with other maintenance treatments (e.g. anti-convulsants, antidepressants) are necessary. Outcomes relating to death and suicidal behaviour should be included in all future maintenance studies of mood disorder.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Lithium for maintenance treatment of mood disorders

This systematic review investigated the efficacy of lithium compared to that of placebo in the maintenance treament of mood disorders (unipolar and bipolar disorder). Nine randomised studies (reporting on 825 participants) were included in the review. Lithium was more effective than placebo in preventing relapse in mood disorder overall. Lithium was more effective than placebo in bipolar disorder, though estimates of the size of the effect varied between studies. In unipolar disorder, lithium appeared to be more effective than placebo but the evidence for this was less clear cut.
Lithium should be considered for maintenance treatment in bipolar disorder and, although the evidence is less reliable, it may be considered as one of a range of treatments with possible benefit in preventing relapse in unipolar disorder. When considering lithium maintenance therapy, patients and clinicians should take into account the evidence of efficacy, side effects and the individual's likely adherence to the recommended treatment regimen. Caution should be exercised in abruptly stopping lithium therapy in patients who have been taking it successfully for some time, due to the high risk of relapse.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

鋰鹽對於情感性疾病的維持治療

情感性疾病是常見的、造成失能的以及會反復發作。它們造成了高自殺風險。維持治療,目的在預防復發,是非常重要的。鋰鹽數年來一直是治療雙極性情感性疾病的主流藥物,但對單極性疾病就比較少用。然而,預防性鋰鹽治療的效力以及有效性一直被爭論著。鋰鹽治療的病人的低自殺率使得鋰鹽被宣稱有特別抗自殺的效果。雖然如此,但是這樣的重要性對一般精神疾病治療上,在預防自殺方面並沒有令人信服的效果。

目標

1.為了檢視鋰鹽治療在預防情感性疾病復發上的效力。2.為了檢驗鋰鹽治療的效果,在使用者的整體健康和社會功能、使用者的接受度以及治療的副作用上的影響。3.為了檢視鋰鹽具有以下假設:在情感性疾病患者有降低自殺和蓄意自傷發生率的特殊效果。

搜尋策略

The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) and The Cochrane Controlled Clinical Trials Register (CCTR) 被搜尋。相關文獻參考資料清單以及主要情感性疾病的教科書都被檢視。作者和其他藥廠專家被聯繫來確認發表或未發表的合適試驗。關於鋰鹽的專業期刊則是以手動搜尋。

選擇標準

隨機對照試驗比較了鋰鹽和安慰劑在維持治療和預防的差異。受試者包含所有年齡被診斷出情感性疾病的男性或女性。終止的研究(所有受試者在隨機分配到繼續鋰鹽治療或安慰劑替代治療之前已經在鋰鹽下穩定一段時間)被排除。

資料收集與分析

資料由兩位評論者從原始文獻報告摘錄出來。研究的主要結果和上述提到的目標是相關的。資料對所有情感性疾病的診斷,雙極性或單極性疾病做個別分析。使用Review Manager version 4.0做資料分析。

主要結論

九個研究被納入此回顧,報告了825位受試者隨機分配到鋰鹽或是安慰劑。對整體情感性疾病和雙極性疾病的預防復發而言,鋰鹽發現比安慰劑更有效。在雙極性疾病有最持續的效果(random effects OR 0.29; 95% CI 0.09 to 0.93)。在單極性疾病方面,直接的治療效果還是偏好鋰鹽,但是結果(研究間的異質性是被允許的)未達到統計上的意義。相當的異質性存在於包含所有族群的研究之間。治療效果的傾向在所有的研究都相同;沒有研究發現鋰鹽有負向的效果。異質性可能是因為受試者選擇不同的差異或是研究前對鋰鹽暴露的不同,導致了終止效應的不同影響。由於不同的治療狀況或是受試者對治療看法不同的影響下,在整體健康和社會功能方面只有少許的資料。描述性分析顯示,整體健康和社會功能的評估一般還是偏好鋰鹽使用。由於死亡或自殺個案的極小數目以及缺乏非致死性自殺行為的資料,使得做出鋰鹽治療具預防自殺的角色這樣有意義的結論是不可能的。

作者結論

這篇系統性回顧文章指出鋰鹽對雙極性疾病是一個有效的維持治療。在單極性疾病方面,有效的證據就不是那麼強而有力。這篇回顧並沒有涵蓋鋰鹽和其他維持治療(目前還不清楚)比較的相對效力。從這篇回顧並沒有確切的證據指出鋰鹽是否有抗自殺的效果。系統性回顧以及大規模隨機研究來比較鋰鹽和其他維持治療(抗痙攣劑,抗憂鬱劑)是需要的。和死亡以及自殺行為相關的結果都應該納入在所有未來情感性疾病維持治療的研究中。

翻譯人

本摘要由彰化基督教醫院謝明翰翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

這篇系統性回顧檢視了鋰鹽和安慰劑在情感性疾病(單極性以及雙極性疾病)維持療法上治療效力的比較。九個隨機研究(825位受試者)被納入此篇回顧。對整體情感性疾病的預防復發而言,鋰鹽發現比安慰劑更有效。對雙極性疾病而言,鋰鹽也比安慰劑更有效,雖然效用大小的評估在研究間不同。在單極性疾病,鋰鹽似乎比安慰劑有效,但是證據不是很清楚。鋰鹽應該被認為是雙極性疾病的維持治療,雖然可靠證據較少,但還是被認為治療範圍內對單極性疾病的預防復發可能有幫助。當考慮到鋰鹽的維持治療,病人和臨床醫師應該考慮到治療效力的證據,副作用以及個人對建議治療方式可能會有順從性的問題。對於已經成功服用鋰鹽一段時間的病人,突然的停藥必須非常謹慎小心,因為復發的風險很高。