Lamotrigine for schizophrenia
Editorial Group: Cochrane Schizophrenia Group
Published Online: 18 OCT 2006
Assessed as up-to-date: 22 AUG 2006
Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Premkumar TS, Pick J. Lamotrigine for schizophrenia. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD005962. DOI: 10.1002/14651858.CD005962.pub2.
- Publication Status: Edited (no change to conclusions)
- Published Online: 18 OCT 2006
Treating the 20-30% of people with schizophrenia whose symptoms are resistant to treatment can be problematic. Adding lamotrigine to ongoing antipsychotic treatment has shown to be of benefit in preliminary studies.
To evaluate the effects of adjuvant lamotrigine for people with schizophrenia and schizophrenia-like psychoses.
We searched the Cochrane Schizophrenia Group's Register (February 2006) and inspected references of all identified studies for further trials. We contacted relevant authors of trials for additional information.
We included all clinical randomised trials comparing lamotrigine with placebo or other antipsychotic augmentation strategies.
Data collection and analysis
We extracted data independently. For homogenous dichotomous data we calculated random effects relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD).
We found five relevant trials (total n=537), but no usable data on service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment or economic outcomes. Overall, reporting of data was poor. Those data we were able to use suggested that equal proportions of people allocated lamotrigine or placebo had no global response (n=208, 1 RCT, RR 1.06 CI 0.73 to 1.54). There was no significant difference between groups in the proportions of people whose mental state did not improve (n=297, 3 RCT, RR 1.26 CI 0.81 to 1.97). There was, however, a significant reduction in the PANSS total scores (n=67, 2 RCT, WMD -16.88 CI -8.57 to -25.18, p=0.0001), positive symptom sub-scale scores (n=65, 2 RCTs, WMD -5.10 CI -8.86 to -1.34) and negative symptom sub-scale scores (n=67, 2 RCTs, WMD -5.25, CI -7.07 to -3.43). Most cognitive measures showed no differences (n=329, 2 RCTs, RR not attaining BACS composite score of 0.5 1.10 CI 0.59 to 2.04). The proportion of participants leaving studies was about 25% at 12 weeks (n=537, 5 RCTs, RR 0.96 CI 0.71 to 1.29). The lamotrigine group did experience the outcome of any adverse effects significantly more frequent than people allocated placebo (n=429, 2 RCTs, RR 1.19 CI 1.02 to 1.38, NNH 10 CI 5 to 90). Among the many effects listed, only nausea was found to be significantly more (9%) in the lamotrigine group compared with placebo (n=465, 3 RCTs, RR 2.26 CI 1.05 to 4.88).
Evidence for use of lamotrigine as an adjuvant for people with schizophrenia is not robust and large well-designed, conducted and reported real-world randomised trials are needed to determine its place in everyday clinical practice.
Plain language summary
Lamotrigine for schizophrenia
Schizophrenia is a major mental disorder affecting about 1% of the general population. The symptoms of the disorder significantly affect the social, occupational and interpersonal functioning of the affected person. In spite of promising treatments for schizophrenia over the last fifty years, at least one-fifth to one-third of affected people fail to respond to treatment. In such cases, additional drugs may be administered to improve treatment response. One such drug is lamotrigine, which was introduced primarily for epilepsy ('fits'). So far there has not been any systematic analysis of those reports that have suggested the benefit of lamotrigine for people with schizophrenia, hence we undertook this review.
We searched major medical databases for studies that have examined the use of lamotrigine for people with schizophrenia. We identified five relevant studies that were conducted according to existing standards of research. A total of 537 people with schizophrenia participated in these five studies. The participants were resistant to various degrees to usual treatments and were randomised to receive either lamotrigine or placebo in addition to their usual drugs. The data regarding effectiveness could only be usefully analysed in less than 70 participants. Lamotrigine was considered to be effective if the questionnaire scores showed a greater reduction than for those who received placebo. The magnitude of this effect was small when compared to placebo.
Data regarding adverse effects were available from three studies. There was a higher occurrence of nausea in those receiving lamotrigine. Apart from this the common side effects were headache and dizziness.
The current evidence does not suggest that the addition of lamotrigine is a remarkable strategy for people with resistant schizophrenia, but the results are suggestive of a positive effect on the symptoms of schizophrenia. However, more studies with larger number of participants are needed to confirm the true magnitude of benefit and safety. This review is limited by the poor presentation of data from the individual studies.
20 – 30%的治療頑抗型精神分裂症患者，其治療是一個問題。Lamotrigine加上現行的抗精神病藥，在初步研究顯示是有益處的。
我們搜尋了Cochrane Schizophrenia Group's Register(2006年2月)及審查所有確定研究進一步試驗的相關文獻，我們也接洽試驗相關作者以獲得額外資訊。
我們發現5個相關試驗(總共537位個案)，但沒有治療結果、一般功能、行為、治療的配合、治療的滿意及經濟結果的資料。整體而言，資料報告顯示是不佳的，這些數據我們可以推論平均比例分配在lamotrigine及安慰劑兩組整體上並無反應(n = 208, 1 RCT, RR 1.06 CI 0.73 to 1.54)。在並無改善的人所佔比例，在兩組並無差異(n = 297, 3 RCT, RR 1.26 CI 0.81 to 1.97)。然而在PANSS整體(n = 67, 2 RCT, WMD −16.88 CI −8.57 to −25.18, p = 0.0001)，PANSS正向症狀次量表(n = 65, 2 RCTs, WMD −5.10 CI −8.86 to −1.34)，PANSS負向症狀次量表(n = 67, 2 RCTs, WMD −5.25, CI −7.07 to −3.43)有顯著差異。大部分認知測量顯示兩組並無差異(n = 329, 2 RCTs, RR not attaining BACS composite score of 0.5 1.10 CI 0.59 to 2.04)。參與試驗個案在12週統計離開試驗約為25%(n = 537, 5 RCTs, RR 0.96 CI 0.71 to 1.29)。所有副作用方面，lamotrigine組並沒有比安慰劑組明顯出現頻繁(n = 429, 2 RCTs, RR 1.19 CI 1.02 to 1.38, NNH 10 CI 5 to 90)。在眾多副作用中，只有噁心在lamotrigine組(9%)有明顯多餘安慰劑組(n = 465, 3 RCTs, RR 2.26 CI 1.05 to 4.88)。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
精神分裂症是重大心理疾患，影響了1%的人口，它的症狀顯著影響社會、職業及人際功能，儘管在這50年精神分裂症的治療有重大的進展，至少五分之ㄧ到三分之ㄧ的患者對治療反應無效，這些個案，額外其他藥物的使用可能可以改善治療反應，其中之ㄧ就是lamotrigine，它原本是被用來處理癲癇的(小發作)，到目前為止，沒有關於這些lamotrigine可能有益於精神分裂症研究的系統回顧分析，因此我們作此回顧。 我們搜尋主要醫學資料庫，找關於lamotrigine使用在精神分裂症患者的研究，我們找到了5個依照現存標準研究執行的相關試驗，參與者對各種程度治療到一般治療反應頑抗，然後隨機被分配到額外加上lamotrigine或安慰劑，關於成效資料只有在70位參與者以下能被有效分析，lamotrigine較安慰劑在問卷量表分數顯示大量減低被認為是有效，當和安慰劑比較，這個效果強度是小的。 關於副作用的資料，從三個試驗中可獲得，在接受lamotrigine有比較高的機會出現噁心，除了這是常見的副作用外，另外是頭痛和頭暈。 目前證據並不意味著使用加成lamotrigine在頑抗治療精神分裂症患者是個傑出的策略，但回顧結果顯示在精神分裂症的症狀是有正面的效果的，然而，更多大量參與者的試驗是必要的，以確定益處及安全性真正的強度。這個回顧受限於各別試驗資料呈現的不足。