Lithium for maintenance treatment of mood disorders
Editorial Group: Cochrane Depression, Anxiety and Neurosis Group
Published Online: 23 JUL 2001
Assessed as up-to-date: 18 MAR 2001
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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.
- Publication Status: Edited (no change to conclusions)
- Published Online: 23 JUL 2001
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.
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.
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other experts in the field and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished.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.
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.
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.
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
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.
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。
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。
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。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。