Depot fluspirilene for schizophrenia

 

Abstract

Background

Antipsychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders. Long-acting depot injections of drugs such as fluspirilene are extensively used as a means of long-term maintenance treatment.

Objectives

To review the effects of depot fluspirilene versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes.

Search methods

We searched the Cochrane Schizophrenia Group's Register (September 2005), inspected references of all identified studies, and contacted relevant pharmaceutical companies.

Selection criteria

We included all relevant randomised trials focusing on people with schizophrenia where depot fluspirilene, oral anti-psychotics, other depot preparations, or placebo were compared. Outcomes such as death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment were sought.

Data collection and analysis

Studies were reliably selected, quality rated and data extracted. For dichotomous data, we calculated relative risk (RR) with the 95% confidence intervals (CI). Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. We summated normal continuous data using the weighted mean difference (WMD). We presented scale data only for those tools that had attained pre-specified levels of quality.

Main results

We included twelve randomised studies in this update of which five are additional studies. One trial compared fluspirilene and placebo and did not report important differences in the global improvement (n=60, 1 RCT, RR "no important improvement "0.97 CI 0.9 to 1.1). Though movement disorders (n=60, 1 RCT, RR 31.0 CI 1.9 to 495.6, NNH 4) were found only in the fluspirilene group, there were no convincing data showing the advantage of oral chlorpromazine or other depot antipsychotics over fluspirilene decanoate. We found no difference between depot fluspirilene and other oral antipsychotics with regard to relapses or to the number of people leaving the study early. Global state data (CGI) were not significantly different, in the short term when comparing fluspirilene with other depots (n=90, 2 RCTs, RR "no important improvement" 0.80 CI 0.2 to 2.8). No significant difference were apparent between fluspirilene and other depots with respect to the number of people leaving the trial early (n=83, 2 RCTs, RR 0.55 CI 0.1 to 2.3) or relapse rates (n=109, 3 RCTs, RR 0.55 CI 0.1 to 2.3). Extrapyramidal adverse effects were significantly less prevalent in the fluspirilene groups (n=164, 4 RCTs, RR 0.50 CI 0.3 to 0.8, NNH 5). Other adverse effects were not significantly different. Attrition in the one comparison between fluspirilene in weekly versus biweekly administration (n=34, RR 3.00 CI 0.1 to 68.8) and relapse rates (n=34 RR 3.18 CI 0.1 to 83.8) were not significantly different. There were no significant difference for movement disorders in one short term study. No study reported on hospital and service outcomes or commented on participants' overall satisfaction with care. Economic outcomes were not recorded by any of the included studies.

Authors' conclusions

Participant numbers in each comparison were small and we found no clear differences between fluspirilene and oral medication or other depots. The choice of whether to use fluspirilene as a depot medication and whether it has advantages over other depots cannot, at present, be informed by trial-derived data. Well-conducted and reported randomised trials are still needed to inform practice.

 

Plain language summary

Depot fluspirilene for schizophrenia

Schizophrenia is a serious, chronic and relapsing mental illness with a worldwide lifetime prevalence of about one percent. Antipsychotic drugs are the mainstay of treatment for schizophrenia, but compliance with medication is often poor due to the adverse effects profile of the drugs and/or the patient's beliefs about their illness. Non-compliance with medication is a major cause of relapse with significant personal, social and economic costs.

Depot antipsychotics were developed in the 1960's specifically to promote treatment compliance and gave rise to extensive use of depots as a means of long-term maintenance treatment. Depot antipsychotics are administered intramuscularly and the drug is released into the body slowly over an extended period of time. These antipsychotics need to be injected only once every 2-4 weeks.

Fluspirilene is a relatively long-acting injectable depot antipsychotic drug used for schizophrenia. We updated the original systematic review (David 1999) on Depot fluspirilene for schizophrenia with five additional studies. Twelve randomised trials are included. Study sizes are small and most were of short term duration. This cannot be very informative for a drug that is meant for long-term maintenance treatment. However, from the studies we were able to include, fluspirilene decanoate does not differ greatly from other depot antipsychotics (fluphenazine decanoate, fluphenazine enathate, perphenazine onanthat, pipotiazine undecylenate) with respect to treatment efficacy, response or tolerability. Outcomes suggest that fluspirilene does not differ significantly from oral antipsychotics or in different weekly regimens, although much cannot be inferred because of the shortage of trials.

 

摘要

背景

使用長效針劑(Depot)fluspirilene治療精神分裂症(schizophrenia)

抗精神病藥物是精神分裂症及類似精神病的主要治療藥物。長效針劑藥物譬如fluspirilene被廣泛當作一種長期維持的治療方式

目標

回顧長效針劑fluspirilene之於安慰劑、口服抗精神病藥物及其他長效針劑對於精神分裂症患者的臨床、社交與經濟層面的療效比較

搜尋策略

我們搜尋Cochrane Schizophrenia Group's Register (September 2005)，同時審視所有合適的研究的參考文獻，並聯繫相關的藥廠

選擇標準

我們涵蓋所有比較長效針劑fluspirilene、口服抗精神病藥物及其他長效針劑的抗精神病藥物或安慰劑的相關隨機試驗。結果諸如死亡、整體功能有臨床顯著的變化、精神狀態、復發、住院治療、副作用及對治療的接受度都被找出來

資料收集與分析

所有的研究都被審慎地選擇、檢視並提取相關數據資料。對於二項式分布的資料，我們計算其相對風險(relative risk)並包含95%的信賴區間(confidence interval)，條件允許的話，也會去計算出需要被治療的病人數目NNT(the number needed to treat)這個統計量。分析方式採用治療意向分析法(intention to treat)。我們使用加權平均差來總結正常連續性資料。對於符合原先設定標準的量測工具才會呈現出它的尺度資料

主要結論

在這次更新的文章中我們總共納入12個採隨機分配的研究，其中5個是這次才新加入的研究。其中一個研究比較fluspirilene與安慰劑的效果，對於整體的改善程度並沒有顯示出特別的差異(n = 60, 1 RCT, RR “no important improvement” 0.97 CI 0.9 to 1.1)。雖然動作障礙(n = 60, 1 RCT, RR 31.0 CI 1.9 to 495.6, NNH 4)僅在長效針劑fluspirilene decanoate組發現，但是沒有具說服性的資料顯示口服chlorpromazine或其他種長效針劑的效果會比較好。就長效針劑depot fluspirilene與其他口服抗精神病藥物來比，在復發率及提前離開研究的人數上並沒有差異。以臨床整體臆斷(CGI)而言，短期使用fluspirilene與短期使用其他長效針劑並沒有顯著的差異(n = 90, 2 RCTs, RR “no important improvement” 0.80 CI 0.2 to 2.8)，同樣的情況也顯現在提前離開研究的人數(n = 83, 2 RCTs, RR 0.55 CI 0.1 to 2.3)或復發率(n = 109, 3 RCTs, RR 0.55 CI 0.1 to 2.3)這兩項指標上。使用fluspirilene顯著地較少發生椎體外徑副作用(n = 164, 4 RCTs, RR 0.50 CI 0.3 to 0.8, NNH 5)，至於其它的副作用則沒有顯著的差異。比較使用fluspirilene每週與每兩週給予的方式，在人數的退出率(n = 34, RR 3.00 CI 0.1 to 68.8)及復發率(n = 34 RR 3.18 CI 0.1 to 83.8)上都沒有顯著差異。此外，有一個短期的研究顯示動作障礙並沒有顯著差異。目前還沒有研究觸及住院和服務相關的指標或者受試者對治療的整體滿意度，而在本次涵蓋的研究裡，也沒有在經濟相關的指標上多所著墨

作者結論

受試者人數在每個比較都不大，我們發現fluspirilene與口服藥物或其他針劑沒有明顯的差異。從試驗上的資料無法顯示選擇fluspirilene作為長效針劑比其他的針劑更好。良好執行與報告的隨機試驗仍需要來確定這樣的臨床服務

翻譯人

本摘要由彰化基督教醫院李柏賢翻譯

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

總結

簡言之，精神分裂症是一個嚴重、慢性及高復發率的精神疾病，全球的終生盛行率約為1%。抗精神病藥物是目前主流的治療，但葯物順從性常常因為副作用及病人對疾病的認知而不佳。藥物不順從是復發的主因，伴隨明顯個人、社會及經濟的損失。抗精神病針劑從1960年代發展來特別增強治療的順從性而被廣泛當作長期維持治療的方式。長效針劑由肌肉注射，藥物以緩慢方式長時間在身體中釋放。這樣的抗精神病藥物只需每2到4週施打一次。fluspirilene是使用在精神分裂症的長效抗精神病藥物。我們更新原來對長效針劑fluspirilene的系統回顧(David 1999)，額外增加五篇研究。共包含了12個隨機試驗。試驗的樣本數都不大且多數為短期的研究。這對作為長期維持性治療而言，沒有提供太多的資料。然而從這些研究，我們的結論是長效針劑fluspirilene與其他長效抗精神病藥物(fluphenazine decanoate, fluphenazine enathate, perphenazine onanthat, pipotiazine undecylenate)在治療效果、反應、耐受性沒有明顯不同。結果建議fluspirilene與口服抗精神病藥物或不同週數的給予方式並沒有顯著差異，雖然因為缺乏研究而無法做更多的推論。 ◆簡言之，精神分裂症是一個嚴重，慢性及高復發的精神疾病，全球的終生盛行率約1%。抗精神病藥物是目前主流的治療，但藥物順從性常常因為副作用及/或病人對疾病的認知而欠佳。藥物順從度不佳是疾病復發的主因，並因此造成明顯個人、社會及經濟上的損失。長效抗精神病針劑發展於1960年代，主要用來增進對藥物的順從性並漸漸地被廣為使用在長期的維持性治療上。長效針劑由肌肉注射，藥物以緩慢方式長時間在身體中釋放。這樣的抗精神病藥物只需每2到4週施打一次。Fluspirilene是一種使用在精神分裂症相對長效的可注射性抗精神病藥物。我們對於原來有關使用flusipirilene治療精神分裂症的系統回顧文章(David 1999)做更新，同時額外增加五篇研究文章，所以總共包含了12個隨機試驗，不過試驗的樣本數都不大而且多為短期的研究，這對於有意作為長期維持性治療的此藥而言，並無法為這部分提供支持性的資料。然而從這些研究當中，我們的結論是長效針劑fluspirilene與其他長效抗精神病藥物(fluphenazine decanoate, fluphenazine enathate, perphenazine onanthat, pipotiazine undecylenate)在治療效果、反應及耐受性上沒有明顯不同，另外，雖然因為研究數量不多而無法做更多的推論，不過在預後的評量上，fluspirilene與口服抗精神病藥物或不同週數的注射頻率間並沒有顯著差異存在