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Intervention Review

Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents

  1. Sarah E Hetrick1,*,
  2. Sally N Merry2,
  3. Joanne McKenzie3,
  4. Per Sindahl4,
  5. Michelle Proctor5

Editorial Group: Cochrane Depression, Anxiety and Neurosis Group

Published Online: 18 JUL 2007

Assessed as up-to-date: 29 MAR 2007

DOI: 10.1002/14651858.CD004851.pub2


How to Cite

Hetrick SE, Merry SN, McKenzie J, Sindahl P, Proctor M. Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004851. DOI: 10.1002/14651858.CD004851.pub2.

Author Information

  1. 1

    Orygen Youth Health Research Centre; Headspace (The National Youth Mental Health Foundation), Centre of Excellence in Youth Mental Health, Melbourne, Victoria, Australia

  2. 2

    University of Auckland, Department of Psychological Medicine, Auckland, New Zealand

  3. 3

    Monash Institute of Health Services Research, Australasian Cochrane Centre, Clayton, Victoria, Australia

  4. 4

    LEO Pharma A/S, Pharmacovigilance, Copenhagen OE, Denmark

  5. 5

    Department of Corrections , Psychological Service , Auckland, New Zealand

*Sarah E Hetrick, Centre of Excellence in Youth Mental Health, Orygen Youth Health Research Centre; Headspace (The National Youth Mental Health Foundation), University of Melbourne, Locked Bag 10, 35 Poplar Road, Parkville, Melbourne, Victoria, 3052, Australia. shetrick@unimelb.edu.au.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 18 JUL 2007

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Depressive disorders are common in young people and are associated with significant negative impacts. Selective serotonin reuptake inhibitors (SSRIs) are often used, however, evidence of their effectiveness in children and adolescents is not clear. Furthermore, there have been warnings against their use in this population due to concerns about increased risk of suicidal ideation and behaviour.

Objectives

To determine the efficacy and adverse outcomes, including definitive suicidal behaviour and suicidal ideation, of SSRIs compared to placebo in the treatment of depressive disorders in children and adolescents.

Search methods

We searched the CCDAN Trials Register, MEDLINE, PSYCHINFO and CENTRAL. Reference lists were checked, letters were sent to key researchers and internet databases searched.

Selection criteria

We included published and unpublished randomised controlled trials.

Data collection and analysis

Two or three review authors selected the trials, assessed the quality and extracted trial and outcome data. We used a fixed-effect meta-analysis. The relative risk was used to summarise dichotomous outcomes and the mean difference to summarise continuous measures.

Main results

Twelve trials were eligible for inclusion, with ten providing usable data. At 8-12 weeks, there was evidence that children and adolescents 'responded' to treatment with SSRIs (RR 1.28, 95% CI 1.17 to 1.41). There was also evidence of an increased risk of suicidal ideation and behaviour for those prescribed SSRIs (RR 1.80, 95% CI 1.19 to 2.72). Fluoxetine was the only SSRI where there was consistent evidence from three trials that it was effective in reducing depression symptoms in both children and adolescents (CDRS-R treatment effect -5.63, 95% CI -7.38 to -3.88), and 'response' to treatment (RR 1.86, 95% CI 1.49 to 2.32). Where rates of adverse events were reported, this was higher for those prescribed SSRIs.

Authors' conclusions

Caution is required to interpret the results. First, there were methodological issues, including high attrition, issues regarding measurement instruments and clinical usefulness of outcomes, often variously defined across trials. Second, patients seen in clinical practice are likely to be more unwell, and at greater risk of suicide, compared to those in the trials, and it is unclear how this group would respond to SSRIs. This needs to be considered, along with the evidence of an increased risk of suicide related outcomes in those treated with SSRIs. It is unclear what the effect of SSRIs is on suicide completion. While untreated depression is associated with the risk of completed suicide and impacts on functioning, it is unclear whether SSRIs would modify this risk in a clinically meaningful way.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Selective serotonin reuptake inhibitors (new generation antidepressants) for depressive disorders in children and adolescents

Depressive disorders are common in young people and have significant negative impacts. Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of depressive disorder in children and adolescents. The review of 12 trials highlighted limitations with the data, making it difficult to answer questions about the effectiveness and safety of SSRIs in clinical practice. Overall, there was evidence of greater reduction in depressive symptoms to a predetermined level deemed a "response" on SSRI compared to placebo. However, response was variously defined across trials making interpretation of this outcome difficult. Fluoxetine was the only SSRI where there was consistent evidence from three trials showing that it was effective in reducing symptoms of depressive disorder in both children and adolescents. Those receiving fluoxetine had a greater improvement, scoring on average 5.63 lower on the Children's Depression Rating Scale-Revised (CDRS-R) scale (range 17-113) than those on placebo. It is unclear whether this small difference is a meaningful outcome for children and adolescents with depressive disorders. Nor is it apparent how children and adolescents with co-morbid conditions and at risk of suicide would respond to SSRIs, given this group were largely excluded from the trials.

There is evidence that those prescribed SSRIs are at an increased risk of suicidal ideation and attempts (RR 1.80, 95% CI 1.19 to 2.72) consistent with a number of similar reviews in the area. Additionally, there was an increased risk of other adverse events. It is unclear how this relates to the risk of suicide completion. The trials were not designed to measure any of the suicide related outcomes adequately. At the same time, untreated depression is associated with the risk of completed suicide and impacts on academic and social functioning, however, it is not clear whether treatment with an SSRI will modify this risk in a clinically meaningful way for children and young people.

Clinicians need to provide accurate information to children and adolescents and their families about the uncertainties regarding the benefits and risks of SSRI medication for depressive disorders.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

使用選擇性血清素再回收抑制劑(SSRIs)治療兒童與青少年的憂鬱疾患

憂鬱疾患常見於年輕人,而且會造成明顯的負面影響。選擇性血清素再回收抑制劑(SSRIs)雖然常被使用,不過用在兒童與青少年身上的療效如何仍然不甚清楚。由有甚者,有報告指出,使用這類藥物會增加兒童與青少年的自殺意念及行為而發出警語。

目標

為了瞭解選擇性血清素再回收抑制劑(SSRIs)之於安慰劑對於兒童與青少年憂鬱疾患的療效以及包括自殺意念及行為等的副作用。

搜尋策略

我們搜尋幾個電子資料庫,包括CCDAN試驗登錄、MEDLINE、PSYCHINFO以及CENTRAL等,也找尋文章的參考文獻,也會寄信給主要的研究者詢問,同時搜尋網路的資料庫。

選擇標準

我們納入了發表與未發表的隨機對照試驗

資料收集與分析

有兩到三位審核的人來挑選研究試驗、評估品質以及擷取研究的成效評估數據。我們使用固定效應模式來執行後設(統合)分析,同時分別使用相對危險性(relative risk)以及平均差來總結二元資料以及連續變項資料。

主要結論

12個試驗合乎納入標準,其中10個試驗的數據無法使用。有證據顯示,兒童和青少年在8 – 12週時對選擇性血清素再回收抑制劑(SSRIs)的治療‘有反應’(RR 1.28, 95% CI 1.17 to 1.41);證據也顯示出處方選擇性血清素再回收抑制劑(SSRIs)也增加了自殺想法和行為的風險(RR 1.80, 95% CI 1.19 to 2.72)。有三個試驗持續顯示出Fluoxetine是惟一一種對兒童與青少年均可減少憂鬱症狀(CDRSR treatment effect −5.63, 95% CI −7.38 to −3.88)以及對治療‘有反應’(RR 1.86, 95% CI 1.49 to 2.32)的選擇性血清素再回收抑制劑(SSRIs)。另外,使用選擇性血清素再回收抑制劑(SSRIs)的副作用比較高。

作者結論

解釋這些結果時需要留意:第一,這裡有些方法學上的問題,包括了高縮減率(attrition rate)、使用的測量工具以及成效評估的臨床實用性等,這在不同的試驗中會有不同的定義。第二,臨床患者的實際情況會比實驗的受試者還糟,而且自殺的危險性也比較高,所以這群患者對於選擇性血清素再回收抑制劑(SSRIs)的反應如何還不得而知,同樣地,對於增加自殺危險性這點來說也是如此。至於選擇性血清素再回收抑制劑(SSRIs)對於自殺成功的影響也同樣並不清楚,特別是未經治療的憂鬱疾患與自殺成功的危險性以及功能受損有關,所以選擇性血清素再回收抑制劑(SSRIs)究竟可否改善自殺成功的危險性也是不甚清楚的。

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

選擇性血清素再回收抑制劑(SSRIs)(新一代抗憂鬱劑)治療兒童與青少年的憂鬱疾患。憂鬱疾患常見於年輕人,而且會造成明顯的負面影響。選擇性血清素再回收抑制劑(SSRIs)經常被用來治療兒童與青少年的憂鬱疾患。本篇回顧的12個試驗凸顯出這些資料的侷限性,使得回答有關臨床實務中SSRIs的效果和安全性這種問題變得有困難。不過整體而言,是有證據顯示SSRI比起安慰劑可以大幅減少憂鬱症狀到事前設定的所謂‘有反應’的程度,然而,對於反應的定義每個試驗各自不同,使得在解釋結果上變的不容易。Fluoxetine是唯一一種在三個試驗當中都顯示出可以有效減少兒童與青少年憂鬱疾患症狀的SSRI;接受fluoxetine的(比起安慰劑)可以減少Children Depression Rating ScaleRevised (CDRSR) scale 5.63分(範圍17 – 113),這小小的差異不曉得對於兒童與青少年憂鬱症的預後是否有意義,也不曉得對於有合併症及自殺風險有沒有影響,畢竟這一類的患者大部分是被排除在研究之外的。目前的證據指出,接受SSRIs處方的人有較高的自殺意念與企圖(RR 1.80, 95% CI 1.19 to 2.72),這跟一些類似的回顧文章結論相同,此外,接受藥物也會增加產生其他副作用的機會,不過並不清楚這是否與自殺成功有關,因為這些試驗並沒有嘗試去量測有關自殺的任何指標;此外,未經治療的憂鬱與自殺成功、學業及社會功能受損有關,可惜的是對於兒童及青少年,我們也並不清楚使用SSRI是否會改變這樣的情形而達到臨床上有意義的結果。所以臨床醫師在治療憂鬱疾患時必須要告知患者及他們的家屬有關使用SSRI治療時所面臨的這些不確定性。