Polyunsaturated fatty acid supplementation for schizophrenia

 

Abstract

Background

Limited evidence supports a hypothesis suggesting that the symptoms of schizophrenia may be the result of altered neuronal membrane structure and metabolism. The structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites.

Objectives

To assess the effects of polyunsaturated fatty acids for people with schizophrenia.

Search methods

We have updated the initial searches of 1998, 2002 and 2005 with a search of the Cochrane Schizophrenia Group's Register, November 2008, which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO.

Where necessary, we contacted authors and relevant pharmaceutical companies for additional information.

Selection criteria

We included all randomised controlled trials of polyunsaturated fatty acid treatment for schizophrenia.

Data collection and analysis

Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI) and estimated the number needed to treat (NNT). For continuous data we calculated weighted mean differences (WMD) and their 95% confidence intervals. We also inspected the data for heterogeneity.

Main results

Eight studies are now included in this review. When any dose omega-3 (E-EPA or EPA) is compared with placebo, small short trials suggest that the need for neuroleptics appears to be reduced for people allocated omega-3 supplementation (n=30, 1 RCT, RR 0.73 CI 0.54 to 1.00) and mental state may improve (n=30, 1 RCT, RR not gaining 25% change in PANSS scores 0.54 CI 0.30 to 0.96, NNT 3 CI 2 to 29). There are no differences in the number of people leaving the study early (n=595, 6 RCTs, RR 0.86 CI 0.50 to 1.48). There are few data on the comparison of any dose omega-6 (GLA) with placebo. For movement disorder outcomes, the one small study we found does not show any difference for average short-term endpoint AIMS score (n=16, 1 RCT, WMD 1.30 CI -1.96 to 4.56). When any dose omega-3 (E-EPA or EPA) is compared with any dose omega-3 (DHA) there is no significant difference for mental state outcome of not gaining 25% change in PANSS scores (n=31, 1 RCT, RR 0.66 CI 0.39 to 1.11). When different doses of omega-3 (E-EPA) are compared with placebo there are no differences in measures of global and mental state between the studies. For the outcome of 'experiencing at least one adverse effect' no differences between groups are found for any dose (1 g/day E-EPA vs placebo n=63, 1 RCT, RR 0.97 CI 0.60 to 1.56; 2 g/day E-EPA vs placebo n=63, 1 RCT, RR 0.67 CI 0.37 to 1.20; 4 g/day E-EPA vs placebo n=58, 1 RCT, RR 1.15 CI 0.72 to 1.82).

Authors' conclusions

Three updates of this review have resulted in more included studies and more people randomised but still relatively little useful additional data. The results remain inconclusive. The new trials all compare the omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid and its ester, ethyl-eicosapentaenoic acid. The use of omega-3 polyunsaturated fatty acids for schizophrenia still remains experimental and this review highlights the need for large, well designed, conducted and reported studies.

 

Plain language summary

Polyunsaturated fatty acid supplementation for schizophrenia

Schizophrenia is a serious mental health problem that affects about one percent of any population. For some people it can become an illness that they have to live with for their entire life. Early research has suggested that supplementing the diet with omega 3 or omega 6 fatty acids may have a positive effect on the symptoms of schizophrenia. This review looks at randomised control trials where omega 3 or omega 6 were used in combination with antipsychotic medication, or as a treatment in their own right for schizophrenia. Eight studies were found which included a total of 517 people who had a diagnosis of schizophrenia or schizoaffective disorder (combined symptoms of schizophrenia and a mood disorder). They ranged from six to 16 weeks in length and were in both hospital and community settings.

The majority of the trials compared two different types of omega 3 fatty acids, EPA (usually as E-EPA) and DHA with placebo, in people with schizophrenia who are stable on antipsychotic medication. Some of these trials show some improvement in general functioning and in mental state but not to a statistically significant degree. In the longest trial there was no difference between the two groups at the end of the study.  One trial compared E-EPA with DHA and found a suggestion that E-EPA works better than DHA, but again it was not statistically significant.  Where EPA was compared to placebo as a first line treatment for schizophrenia (30 people), those taking EPA had a better overall outcome and improvement in mental state.  However, this was a short trial with few people. Finally, one trial compared a type of omega 6 with placebo in men who had the movement disorder tardive dykinesia (16 people). There was no improvement in the symptoms of movement adverse effects in either group at the end of six weeks.       

These trials were both small and short.  In addition most of the data they reported were not able to be used, and half of the trials were funded by the group supplying the trial medication. Therefore it is still not clear whether taking manufactured omega 3 or 6 improves overall functioning or mental state in people with schizophrenia.

(Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org)

 

摘要

背景

精神分裂症的多元不飽和脂肪酸補充

有限的證據支持精神分裂症症狀可能是神經膜結構和代謝的改變所致.結構和代謝有賴於必需脂肪酸在血中濃度和他們的代謝物.

目標

評估在精神分裂症病人補充多元不飽和脂肪酸的效果

搜尋策略

我們已經更新1998,2002, 2005年一開始的搜尋,搜尋2008年11月考科藍精神分裂症族群的登錄,此登錄是奠基於規則的搜尋CINAHL, EMBASE, MEDLINE 及 PsycINFO. 有需要時，我們與作者和相關藥廠接觸以獲得額外的資訊

選擇標準

將所有給予精神分裂症多元不飽和脂肪酸的隨機對照試驗納入

資料收集與分析

我們獨立地針對研究做品質評估和擷取相關的資料. 計算相對風險(Relative Risk) 及其 95% confidence intervals (CI),並估算number needed to treat (NNT).針對連續變項,我們計算weighted mean differences (WMD) 及其95% confidence intervals.我們也檢視資料的異質性.

主要結論

早期離開研究的病人數目並沒有差異. (n = 595, 6 RCTs, RR 0.86 CI 0.50 to 1.48). 鮮少資料去比較不同劑量的omega6 (GLA)與安慰劑.針對運動性疾患的結果,有一篇小的研究顯示,短期的AIMS平均分數沒有任何差異(n = 16, 1 RCT, WMD 1.30 CI −1.96 to 4.56).當不同劑量的omega3 (EEPA or EPA)與不同劑量的omega3 (DHA) 時,並未顯示在心理狀態的這個結果有任何顯著差異,這是以PANSS的分數達25%來定義. (n = 31, 1 RCT, RR 0.66 CI 0.39 to 1.11). 當以不同劑量的omega3 (EEPA)與安慰劑做比較時,在整體心理狀態的這個量測方面並無差異.在至少經歷一種副作用的這個結果,不同劑量的族群也沒有差異. (1 g/day EEPA vs placebo n = 63, 1 RCT, RR 0.97 CI 0.60 to 1.56; 2 g/day EEPA vs placebo n = 63, 1 RCT, RR 0.67 CI 0.37 to 1.20; 4 g/day EEPA vs placebo n = 58, 1 RCT, RR 1.15 CI 0.72 to 1.82).

作者結論

此篇文獻的三份更新導致有更多的研究及更多隨機的病人被納入，但依舊得到相對而言幫助不大的資料.結果仍舊沒有共識.這篇新的試驗比較全部的omega3 多元不飽和脂肪酸(polyunsaturated fatty acids),尤其是二十碳五烯酸及其酯、乙基二十碳五烯酸.以omega3 多元不飽和脂肪酸治療精神分裂症依舊是試驗性的,此篇文獻強調了需要大型的,完善設計及執行的研究.

翻譯人

本摘要由彰化基督教醫院李冠瑩翻譯

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

總結

精神分裂症的多元不飽和脂肪酸補充 :精神分裂症是一嚴重的心理健康問題,影響達任何族群的1%.對某些人來講,它可能變成需終生共存的疾病.早期研究已經建議在飲食中補充omega 3或omega 6脂肪酸對精神分裂症症狀有正向效果.此篇文獻回顧檢視結合omega 3(或omega 6)與抗精神用藥或是他們自己選擇omega 3(或omega 6)作為治療的隨機控制試驗, 有八篇研究被納入,共517位診斷精神分裂症或分裂情感性疾患(結合精神分裂症與情感性疾患)。試驗的天數範圍為6到16週,包含住院和社區病人.試驗大部分是比較兩種安慰劑與不同類型的omega 3 fatty acids EPA (usually as EEPA) and DHA,對象是穩定接受抗精神用藥的精神分裂症患者. 這些試驗有些顯示在一般功能及心理狀態有些改善,但未達統計學上顯著程度.在最長的試驗,兩個族群到研究結束時並未顯示差異.有一個試驗比較EEPA和 DHA,結果建議EEPA優於DHA,但同樣地未達統計學上顯著差異. 當EPA與安慰劑比較,用作精神分裂症的第一線治療時,(針對30個病人),服用EPA的那組整體結果及心理狀態改善程度較佳.然而,這是短期試驗,病人數也較少.最後,有一試驗針對16名運動性疾患遲發性自主運動異常(tardive dykinesia),比較服用omega 6與安慰劑,結果在6週試驗結束時,兩組在運動方面的副作用皆沒有改善. 這些皆是小型且短期的試驗.除此之外,大部分發表的資料都不能夠使用.而且有一半的試驗是由提供試驗藥物的廠商贊助經費.因此究竟服用omega 3 或omega 6 對精神分裂症患者整體功能和心理狀態的改善程度仍舊不清楚.(Janey Antoniou of RETHINK, UK 提供此篇文獻回顧的簡明版摘要說明,見 www.rethink.org)