Low dosage tricyclic antidepressants for depression

  • Review
  • Intervention

Authors

  • Toshi A Furukawa,

    Corresponding author
    1. Nagoya City University Graduate School of Medical Sciences, Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya, Aichi, Japan
    • Toshi A Furukawa, Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan. furukawa@med.nagoya-cu.ac.jp.

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  • Hugh McGuire,

    1. National Coordinating Centre for Women and Child Health, London, UK
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  • Corrado Barbui

    1. University of Verona, Department of Medicine and Public Health, Section of Psychiatry, Verona, Italy
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Abstract

Background

Tricyclic antidepressants are still extensively prescribed worldwide. Evidence for the recommended dosage of tricyclics, however, is poor.

Objectives

To compare the effects and side effects of low dosage tricyclic antidepressants with placebo and with standard dosage tricyclics in acute phase treatment of depression.

Search methods

Electronic search of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), incorporating results of group searches of MEDLINE (1966-), EMBASE (1980-), CINAHL (1982-), PsycLIT (1974-), PSYNDEX (1977-) and LILACS (1982-1999) and hand searches of major psychiatric and medical journals. Reference search and SciSearch of the identified studies. Personal contact with authors of significant papers.

Selection criteria

All randomised controlled trials 1) comparing low dosage TCA (=< 100 mg/d on average at the end of trial) with placebo or 2) comparing low and standard dosages of the same TCA, in acute phase treatment of depressive disorder

Data collection and analysis

Two independent reviewers examined eligibility of the identified studies, and extracted data for outcomes at 1 week, 2 weeks, 4 weeks, 6-8 weeks and later. Main outcome measures were relative risk of response in depression (random effects model), according to the original authors' definition but usually defined as 50% or greater reduction in severity of depression according to the last-observation-carried-forward intention-to-treat method, and relative risks of overall dropouts and dropouts due to side effects. Other outcome measures included worst-case-scenario intention-to-treat analysis of response as defined above (in which dropouts were considered non-responders in the active treatment group and as responders in the comparison group), and standardised weighted mean scores of continuous depression severity scales (usually calculated by last-observation-carried-forward method).

Main results

35 studies (2013 participants) compared low dosage tricyclics with placebo, and six studies (551 participants) compared low dosage tricyclics with standard dosage tricyclics. Low dosage tricyclics, mostly between 75 and 100 mg/day, were 1.65 (95% confidence interval 1.36 to 2.0) and 1.47 (1.12 to 1.94) times more likely than placebo to bring about response at 4 weeks and 6-8 weeks, respectively. Standard dosage tricyclics failed, however, to bring about more response but produced more dropouts due to side effects than low dosage tricyclics.

Authors' conclusions

Treatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of varying dosages.

摘要

背景

低劑量三環類抗鬱劑治療憂鬱症

三環類抗鬱劑仍於全球廣泛使用.建議劑量的證據仍不足.

目標

比較低劑量三環類抗鬱劑,安慰劑和標準劑量三環類抗鬱劑,對治療急性期憂鬱症的療效和副作用

搜尋策略

電子搜尋the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), incorporating results of group searches of MEDLINE (1966), EMBASE (1980), CINAHL (1982), PsycLIT (1974), PSYNDEX (1977) and LILACS (1982 – 1999).也手動搜尋主要精神和醫學期刊,文獻搜尋和挑中視驗的SciSearch.重要論文的作者也做私人接觸.

選擇標準

納入所有隨機對照試驗比較不同治療組別的對治療急性期憂鬱症的療效和副作用.比較組別包含:1)低劑量三環類抗鬱藥 (試驗期末劑量平均 = < 100 mg/d)和安慰劑或2)低劑量和標準劑量

資料收集與分析

兩個檢閱者獨立檢查選出試驗的正確性,擷取1,2,4,6 – 8週和之後的結果資料.主要結果測量值為憂鬱反應的RR(隨機效果模型),總退出RR和因副作用退出RR.反應定義根據各文章原作者的定義,但通常採用意圖治療病人的最後觀察,憂鬱症嚴重度減少50%以上.其他結果變項包含意圖治療病人中的最壞狀況假設分析(定義為:治療組退出者視為沒有反應,對照組退出者則視為有反應)和連續憂鬱嚴重量表標準化加權平均得分(採用意圖治療病人的最後觀察)

主要結論

35試驗(201受試者)比較低劑量三環類抗鬱劑和安慰劑, 6試驗(551受試者)比較 低劑量三環類抗鬱劑和標準劑量的三環類抗鬱劑. 4週和6 – 8週時,低劑量三環類抗鬱劑(大部分介於75和100 mg/day)有療效的機率分別為安慰劑組的1.65倍(95% confidence interval 1.36 to 2.0)和1.47倍(1.12 to 1.94). 與低劑量組相比,沒有較多受試者對標準劑量三環類抗鬱劑有反應,但此高劑量反而帶來使更多受試者因副作用退

作者結論

使用低劑量三環類抗鬱劑治療憂鬱症獲得證實.但需更多嚴謹試驗確定不同劑量間的相對效益和傷害

翻譯人

本摘要由成功大學附設醫院尹子真翻譯。

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

總結

低劑量三環類抗鬱劑治療憂鬱症有效.臨床醫師和心理學家常被批評對憂鬱症患者使用的三環類抗鬱劑劑量太低,系統回顧找到39個試驗(共2564 受試者),且發現三環類抗鬱劑劑量介於75 – 100 mg/day或甚至少於此劑量都比安慰劑能夠減少憂鬱.另方面,沒有強力證據顯示標準劑量三環類抗鬱比低劑量更有效.此發現證明低劑量三環類抗鬱劑治療憂鬱症獲得證實

Plain language summary

Low dose tricyclic antidepressants (TCAs) for depression

Practicing physicians and psychiatrists have often been criticised for administering too low a dosage of tricyclic antidepressants for people with depression. This systematic review of 39 studies (2564 participants) found that tricyclic antidepressants between 75-100 mg/day and possibly below this range result in more reduction in depression than placebo. On the other hand, there was no strong evidence to show that standard dosage tricyclic brings about more response than low dosage tricyclic. The findings suggest that administration of low dosage tricyclic antidepressant is a defensible practice.

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