Trazodone for agitation in dementia
Editorial Group: Cochrane Dementia and Cognitive Improvement Group
Published Online: 19 JUL 2004
Assessed as up-to-date: 10 APR 2008
Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Martinón-Torres G, Fioravanti M, Grimley Evans J. Trazodone for agitation in dementia. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD004990. DOI: 10.1002/14651858.CD004990.
- Publication Status: New search for studies and content updated (no change to conclusions)
- Published Online: 19 JUL 2004
Behavioural and psychiatric disturbances affect at least 50% of people with Alzheimer's disease and other dementias. Neuroleptic drugs are extensively prescribed to treat behavioural manifestations of dementia in spite of only modest efficacy and a high frequency of adverse effects. There is clearly a need for safer and more effective remedies. Trazodone is a psychoactive compound with sedative and antidepressant properties, and with mixed serotonin agonist and antagonist effects. Functional serotonergic deficits may be related to the genesis of behavioural disturbances in dementia.
To determine the clinical efficacy and safety of trazodone, for any type of behavioural or psychological cognition in people with dementia without an additional diagnosis of depression.
The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 23 March 2008 using the terms: trazodone* OR beneficat OR desirel OR sideril OR trazodil OR trazalon. The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources.
All unconfounded, double-blind, randomised controlled trials, comparing trazodone with placebo in managing behavioural and psychiatric symptoms (except depression) in any type of dementia.
Data collection and analysis
Available data for this analysis were extracted from the two included studies and odds ratios or average differences, with 95% confidence intervals, calculated. Intention-to-treat analysis was undertaken where possible.
Two studies were included, comprising 104 participants with dementia. The trials differed in design: one a parallel-group study of patients with Alzheimer's disease and another a cross-over study of patients with frontotemporal dementia with an-open label follow-up trial of three years. The results from this extension study have not been used in the analysis. It was not possible to pool the data. The studies were respectively of 16 and six weeks duration, using trazodone from 50 to 300 mg daily. Both trials examined global clinical state, behavioural disturbances and cognitive function. The parallel study also assessed activities of daily living and caregiver burden. Compared with placebo, the use of trazodone was not associated with statistically significant benefits for behavioural manifestations as measured by various rating scales. Analysis of changes from baseline for clinical impression of change and for cognitive function did not produce statistically significant results in favour of trazodone. A variety of adverse effects were recorded with no significant differences between trazodone and placebo.
There is insufficient evidence to recommend the use of trazodone as a treatment for behavioural and psychological manifestations of dementia. In order to assess effectiveness and safety of trazodone, longer-term randomized controlled trials are needed, involving larger samples of participants with a wider variety of types and severities of dementia.
Plain language summary
Insufficient evidence from randomized, placebo-controlled studies to support a recommendation that trazodone should be prescribed, or not prescribed, for BPSD
The rationale for using trazodone is that it is a sedating atypical serotonergic antidepressant with a low rate of adverse effects and some behavioural and psychological symptoms in people with dementia (BPSD) are associated with serotonergic dysfunction. The conclusion is based on limited data from two small studies. The larger of the studies, conducted in 73 patients with Alzheimer's disease, showed no beneficial effect of trazodone at all. A smaller cross-over study in patients with frontal lobe dementia showed a trend for reduction in some symptoms in the first study period. Larger, longer studies are needed to explore the efficacy, effectiveness and safety of trazodone.
至少50%阿茲海默症及其他癡呆症患者會出現行為及精神障礙。儘管Neuroleptic療效不大而且副作用發生率高，不過卻廣泛用於治療癡呆症患者行為表現，因此實在需要更為安全及有效的藥物。 Trazodone是一種精神刺激性的化合物，具有鎮痛與抗憂鬱的特性，並且具有混合血清胺作用劑(serotonin agonists)及結抗劑的效果。血清氨酸類缺乏可能與癡呆症行為障礙的基因有關。
於2006年6月2日使用trazodon*、beneficat、desirel、sideril、trazodil、trazalon等字彙，搜尋Specialized Register of the Cochrane Dementia and Cognitive Improvement Group以找出試驗。 這個資料庫包含所有主要健康照護資料庫及許多進行中試驗資料庫，此外並且定期更新。
這分析可利用的資料係摘錄自兩納入的研究且預測其可能性或平均差(average differences)，以及其95% CI。合適時會進行治療意向(intentiontotreat)分析。
共納入了2個研究，比較104位失智症患者。試驗在設計上有所差異： – 1個採用平行試驗以失智症患者進行研究，而另外一個則是採用列聯分析以額顳葉失智患者進行研究。因此無法合併數據。 而研究之間的期間從16∼6周都有，而使用trazodone的劑量則由50mg300mg/天，而兩個試驗都檢驗了整體臨床狀況；行為障礙以及認知功能。而該平行試驗還評估了日常活動以及照顧者的負荷程度。 當使用了各種評量尺度評估後發現trazodone與安慰劑相比，並沒有顯著改善行為問題。進行臨床重要結果分析，顯示在臨床印象改變與認知功能方面並沒有偏好支持使用trazodone，不過記錄顯示trazodone與安慰劑有各種不良反應，不過兩者間並沒有顯著差異。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
來自隨機分配、安慰劑對照研究的數據並不足以建議是否應該開立trazodone 治療失智症行為及精神症狀(Behavioural and Psychological Symptoms of Dementia，BPSD)。 使用trazodone的原因在於它是鎮靜用非典型血清抗憂鬱藥物，並且不良反應發生率很低， 而一些失智症患者行為及精神症狀即與血清素障礙有關。 結論是以兩個小型研究為基礎；較大的那個研究以73位阿茲海默症患者進行試驗，顯示trazodone並沒有效益；較小的那個交叉研究以額葉失智患者為對像，顯示某些症狀在研究第一期時有減少的趨勢。 需要大型長期的研究探討trazodone的療效、效益以及安全性。