Active placebos versus antidepressants for depression

 

Abstract

Background

Although there is a consensus that antidepressants are effective in depression, placebo effects are also thought to be substantial. Side effects of antidepressants may reveal the identity of medication to participants or investigators and thus may bias the results of conventional trials using inert placebos. Using an 'active' placebo which mimics some of the side effects of antidepressants may help to counteract this potential bias.

Objectives

To investigate the efficacy of antidepressants when compared with 'active' placebos.

Search methods

CCDANCTR-Studies and CCDANCTR-References were searched on 12/2/2008. Reference lists from relevant articles and textbooks were searched.

Selection criteria

Randomised and quasi randomised controlled trials comparing antidepressants with active placebos in people with depression.

Data collection and analysis

Since many different outcome measures were used a standard measure of effect was calculated for each trial. A subgroup analysis of inpatient and outpatient trials was conducted. Two reviewers independently assessed whether each trial met inclusion criteria.

Main results

Nine studies involving 751 participants were included. Two of them produced effect sizes which showed a consistent and statistically significant difference in favour of the active drug. Combining all studies produced a pooled estimate of effect of 0.39 standard deviations (confidence interval, 0.24 to 0.54) in favour of the antidepressant measured by improvement in mood. There was high heterogeneity due to one strongly positive trial. Sensitivity analysis omitting this trial reduced the pooled effect to 0.17 (0.00 to 0.34). The pooled effect for inpatient and outpatient trials was highly sensitive to decisions about which combination of data was included but inpatient trials produced the lowest effects.

Authors' conclusions

The more conservative estimates from the present analysis found that differences between antidepressants and active placebos were small. This suggests that unblinding effects may inflate the efficacy of antidepressants in trials using inert placebos. Further research into unblinding is warranted.

 

Plain language summary

Tricyclic antidepressants compared with active placebos for depression

This review examined trials which compared antidepressants with 'active' placebos, that is placebos containing active substances which mimic side effects of antidepressants. Small differences were found in favour of antidepressants in terms of improvements in mood. This suggests that the effects of antidepressants may generally be overestimated and their placebo effects may be underestimated.

 

摘要

背景

積極安慰劑與抗鬱劑在憂鬱症的比較

雖然有共識即使抗鬱劑對憂鬱症是有效的，安慰劑效應也被認為是顯著的。來參加或評估者，可能從抗鬱劑的副作用知道可能的藥物，過去使用安慰劑的試驗可能會造成誤差。使用的是‘有作用’的安慰劑，它有一些抗鬱劑的副作用，可能有助於解決這一潛在的誤差。

目標

調查抗鬱劑跟‘積極’安慰劑的療效比較。

搜尋策略

於2008年12月2日搜尋CCDANCTR研究以及CCDANCTR參考文獻。並搜尋相關文獻的參考資料清單以及教科書。

選擇標準

隨機和半隨機對照試驗比較，抗抑鬱藥與積極安慰劑在抑鬱症的人的療效。

資料收集與分析

因為有許多不同的結果測量，於每個試驗以一個經過計算標準衡量的效果使用。一個住院和門診試驗分組分析在進行。兩個回顧者獨立評估是否每個試驗符合納入標準。

主要結論

9個研究，包括了751個參與者。其中兩個提出有影響的結果顯示一貫和統計學顯著性差異有利於活性藥物。結合所有的研究產生了統合的影響估計為0.39標準偏差(信賴區間為0.24到0.54)為抗鬱劑改善情緒。因為一個強烈有統計差異的試驗，產生很高的異質性的。敏感性分析省略這一試驗,降低了集合效應至0.17 (0.00至0.34)。住院和門診試驗的集合效應對於納入數據結合的決定是高度敏感，但住院試驗產生了最低的效果。

作者結論

從目前較為保守的估計分析發現，抗抑鬱劑和積極安慰劑之間的差異小。這表明， unblinding非盲效應可能誇大抗抑鬱藥物在使用惰性安慰劑試驗的療效。進一步研究unblinding是需要的。

翻譯人

本摘要由彰化基督教醫院廖慈凰翻譯。

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

總結

三環抗抑鬱劑僅略優於積極placebos.這回顧檢視了比較抗抑鬱劑與‘積極’安慰劑的試驗，這是安慰劑含有活性物質的模仿抗抑鬱藥的副作用。抗抑鬱藥物在改善情緒稍微有利。這表明，抗抑鬱劑可能普遍被高估和它們的安慰劑效應可能被低估。