Benzodiazepines for schizophrenia

 

Abstract

Background

Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them benzodiazepines.

Objectives

To review the effects of benzodiazepines for the treatment of schizophrenia and schizophrenia-like psychoses.

Search methods

The reviewers searched the Cochrane Schizophrenia Group's register (last search March 2005). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted authors of relevant studies in order to obtain missing data from existing trials.

Selection criteria

All randomised controlled trials comparing benzodiazepine to antipsychotics or to placebo (or no intervention), whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses.

Data collection and analysis

We independently inspected abstracts, selected studies and re-inspected and quality assessed the full reports. We independently extracted relevant outcomes. Dichotomous data were analysed using relative risks (RR) and the 95% confidence intervals (CI). Continuous data were analysed using weighted mean differences. Where possible the number needed to treat (NNT) or number needed to harm (NNH) statistics were calculated.

Main results

The review currently includes 31 studies with over 2000 participants. Most studies were small, of short duration - one to 13 weeks - and inconsistently and incompletely reported.

Eight studies compared benzodiazepines as a sole agent with placebo. More participants receiving benzodiazepines showed a clinically significant response (n=222, 4 RCTs, RR 0.54 CI 0.3 to 1.0, NNT 3 CI 2 to 17). Only one small study found a significant group difference in favour of benzodiazepines regarding the improvement in overall BPRS mental state. Different rating scales were used to assess general mental state, and therefore many outcomes could not be pooled and no overall direction of effect emerged. Some adverse events observed in these studies suggested that benzodiazepines were more harmful than placebos but again the data were incompletely reported and without overall effect.

Thirteen studies examined the effects of benzodiazepines in comparison to antipsychotics as a sole treatment. Trials that reported on clinical response found no advantage for any treatment group concerning improvement of the participants' global state, except of one small study that analysed the mean CGI severity score at one hour. This comparison is highly limited by the low numbers of studies reporting on global function and the short trial duration. Two studies showed a statistically significant superiority of antipsychotics in terms of relapse prevention at one year. Desired sedation occurred significantly more often among participants in the benzodiazepine group than among participants in the antipsychotic treatment group at 20 (n=301, 1 RCT, RR 1.32 CI 1.2 -1.5, NNT 5, CI 3 to 8) and 40 minutes(n= 301, 1 RCT, RR 1.13 CI 1.0 to 1.2, NNT 9 CI 6 to 33), but not at 30, 60 or 12 minutes. Other outcomes relating to the general or specific mental state revealed no significant differences between groups. As far as adverse events were reported there were no results in favour of any group.

Sixteen studies examined whether the augmentation of antipsychotics with benzodiazepines is more effective than antipsychotics as a sole treatment. During the first hour of treatment the combination treatment group benefited from the additional benzodiazepine in terms of the participants´ global state. This benefit diminished over time and was not reproducible at 2 hours or longer. No superior efficacy of benzodiazepine augmentation could be found regarding the general mental state. Specific aspects of the mental state showed no group difference except for desired sedation at 30 and 60 minutes. Somnolence affected the combination treatment group significantly more than the control group (n=118, 2 RCTs, RR 3.30 CI 1.0 to 10.4, NNH 8 CI 5 to 50). We found use of antiparkinson medication to be less frequently used in the combination treatment group (n=282, RR 0.68 CI 0.5 to 1.0, NNT 9 CI 6 to 48). Adverse events were poorly reported and the results were based on very little data.

Authors' conclusions

Randomised trial-derived evidence is currently too poor to recommend benzodiazepines neither as a sole nor as an adjunctive agent in schizophrenia or schizophrenia-like psychoses. The only significant effects were seen in terms of short-term sedation, at best. The evidence available on augmentation of antipsychotics with benzodiazepines is inconclusive and justifies large, simple and well-designed future trials focusing on clinical response, mental state, aggressive behaviour and adverse events.

 

Plain language summary

Benzodiazepines for schizophrenia

Schizophrenia is a long term, chronic illness with a worldwide lifetime prevalence of about one percent. It has a high disability rate and the cost to individuals, their carers and health services is considerable. Antipsychotics are the mainstay of treatment and are generally effective for 'positive' symptoms such as hallucinations, but 'negative' symptoms such as emotional withdrawal are fairly resistant to treatment. Additionally, antipsychotics are associated with disabling side effects such as movement disorders, making compliance with treatment more difficult. Benzodiazepines have been used alone or in combination with antipsychotic medication to treat schizophrenia. We reviewed the effects of benzodiazepines for the treatment of schizophrenia. The results from this review are inconclusive, and larger better designed trials are needed before firm conclusions can be made.

 

摘要

背景

Benzodiazepines治療精神分裂症

許多精神分裂症的病人在使用一般抗精神藥物並無法達到令人滿意的治療反應。在這些案例中，許多額外加入藥物被使用，其中一種為Benzodiazepines。

目標

回顧benzodiazepines在治療精神分裂症和類精神分裂症精神病的效果。

搜尋策略

我們搜索了the Cochrane Schizophrenia Group's register (最後一次搜索為2005年三月)。這個登錄系統是藉由方法性的搜尋BIOSIS、CINAHL、 Dissertation abstracts、 EMBASE、 LILACS、MEDLINE、PSYNDEX、 PsycINFO、RUSSMED、Sociofile，手動收尋適合的期刊和許多正在進行的會議來完成的。我們也聯絡了藥廠公司和相關研究的作者來獲得現存研究中遺失的資料。

選擇標準

我們納入了所有比較benzodiazepine和抗精神病藥物或是安慰劑(或是步介入)的隨機對照試驗，無論是用來單一治療精神分裂症和/或類精神分裂症精神病或是額外加入用來輔助抗精神病藥物療效之用。

資料收集與分析

我們各自獨立檢視摘要,被選擇的研究和重新檢視與品質被確定的完整報告。我們各自獨立的擷取適當的結果。二分法資料以相對危險性(RR),95%信賴區間(CI)來分析。為了連續資料，我們也計算了加權平均差異(WMD)。

主要結論

回顧目前幫過了31個研究中的200個受試者。大部分的研究為小型,短期−1到13週和不一致地和不完全的報導。8個研究將benzodiazepines當作單一治療與安慰劑做比較。大部分接受benzodiazepines的受試者在臨床上顯現出明顯的反應(n = 222, 4 RCTs, RR 0.54 CI 0.3 to 1.0, NNT 3 CI 2 to 17). 只有一個小型的研究發現,如果就整體BPRS精神狀態而言，benzodiazepines有明顯的差異. 不同的評分量表被用來評估整體精神狀態，所以許多結果並無法被一起納入評估且效果的整體方向並未呈現。在這些研究觀察到一些副作用使人聯想到benzodiazepines可能較安慰劑更有害，但資料並未被完整報導且並無整體效應。13個研究檢視單獨使用benzodiazepines和抗精神病藥物比較的效果。除了一個分析在一小時平均CGI嚴重性的一個小型研究，實驗指出在臨床反應針對受試者的改善，整體狀態並無發現任何的治療組有較優勢的結果。這個比較被報導整體功能研究數量的稀少和試驗時間的短少而被高度限制。兩個研究顯示一年內的防止再復發，抗精神病藥有一個令人滿意的明顯優勢。在使用benzodiazepine比使用antipsychotic在20分鐘後(n = 301, 1 RCT, RR 1.32 CI 1.2 −1.5, NNT 5, CI 3 to 8)與40分鐘後(n = 301, 1 RCT, RR 1.13 CI 1.0 to 1.2, NNT 9 CI 6 to 33)可得到令人想要的鎮靜效果,但在30,60或是12分鐘後則否。其他和一般或是特別的精神狀態相關的結果則在這兩組之間無差別。兩組在被報告的副作用則無差異。16個研究顯示抗精神病藥物合併使用benzodiazepines比單獨使用抗精神病藥物更有效率。在第一個小時的治療中，合併使用、額外加入benzodiazepines對合併治療組在急性或是整體狀態有助益。這個助益隨著時間而減少，且在兩個小時或以上時消失。在考慮整體精神狀態下，在額外加入benzodiazepine並無較優的效率。在特別的精神狀態方面顯示除了需要的在30分鐘與60分鐘鎮靜效果之外並無差異. 合併治療組在嗜睡效果比對照組更明顯(n = 118, 2 RCTs, RR 3.30 CI 1.0 to 10.4, NNH 8 CI 5 to 50)。 我們發現在合併治療組有較低的頻率使用antiparkinson藥物(n = 282, RR 0.68 CI 0.5 to 1.0, NNT 9 CI 6 to 48)。額外作用很少被報告且結果是依據非常小的資料。

作者結論

目前的隨機試驗顯示來討論以benzodiazepines單獨或是外加治療治療精神分裂症或是類精神分裂精神病的證據太過薄弱。唯一有意義最好的效果為短期鎮靜方面. 在外加於抗精神病的benzodiazepines可獲得的證據仍為未定的而需要針對臨床反應,精神狀態,侵犯行為和副作用需要更大,簡單和設計良好的更進一步研究。

翻譯人

本摘要由彰化基督教醫院王智仁翻譯。

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

總結

精神分裂症是一個長期,慢性的疾病有著約1%的世界性的終生盛行率。他有高失能的機率和對個案，他們的照護者和健康照護的損失是可觀的。抗精神病藥物是為治療的支柱和對正性症狀如幻覺通常為有效的，但治療對負性症狀如情感退縮相當無效。此外，抗精神病藥物和失能的副作用如動作疾患使得對治療的遵從性更加的困難。Benzodiazepines被用來單獨使用或是與抗精神並藥物一起治療精神分裂症. 我們回顧了Benzodiazepines治療精神分裂症的效果。這個回顧的結果是為未下結論的，而在下確定的結論之前需要更大設計更好的試驗。