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Psychostimulants for depression

  • Review
  • Intervention

Authors

  • Bridget Candy,

    Corresponding author
    1. Royal Free & University College Medical School , Marie Curie Palliative Care Research Unit, Department of Mental Health Sciences, London, UK
    • Bridget Candy, Marie Curie Palliative Care Research Unit, Department of Mental Health Sciences, Royal Free & University College Medical School , Hampstead Campus , Rowland Hill Street , London, NW3 2PF , UK. b.candy@medsch.ucl.ac.uk. bridget@metaclarity.com.

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  • Louise Jones,

    1. Royal Free & University College Medical School, Marie Curie Palliative Care Research Unit, Department of Mental Health Sciences, London, UK
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  • Rachael Williams,

    1. Royal Free & University College Medical School, Marie Curie Palliative Care Research Unit, Department of Mental Health Sciences, London, UK
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  • Adrian Tookman,

    1. Royal Free & University College Medical School, Marie Curie Palliative Care Research Unit, Department of Mental Health Sciences, London, UK
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  • Michael King

    1. Royal Free & University College Medical School, Marie Curie Palliative Care Research Unit, Department of Mental Health Sciences, London, UK
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Abstract

Background

Depression is common, disabling, costly and under-treated. There are problems in the current first-line drug treatment, antidepressants, for moderate or severe depression. There is a body of research that has evaluated the effect of psychostimulants (PS) in the treatment of depression. This has not been reviewed systematically.

Objectives

To determine the effectiveness of PS in the treatment of depression and to assess adverse events associated with PS.

Search methods

Databases CCDANCTR-Studies and CCDANCTR-References were searched on 21/6/2006. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, AMED, CINAHL, Dissertation Abstracts and the National Health Service Research Register were searched.

Selection criteria

Randomised controlled trials (RCTs) assessing the effectiveness of PS were included. The trial population comprised adults of either sex with a diagnosis of depression.

Data collection and analysis

Two review authors extracted the data independently and assessed trial quality. Meta-analysis was considered for trials with comparable key characteristics. The primary outcome was depression symptoms, based on a continuous outcome, using the standardised mean difference (SMD), or a dichotomous measure of clinical response, using odds ratios (OR), with 95% confidence intervals (CI).

Main results

Twenty-four RCTs were identified. The overall quality of the trials was low. Five drugs were evaluated; dexamphetamine, methylphenidate, methylamphetamine, pemoline and modafinil. Modafinil was evaluated separately as its pharmacology is different to that of the other PS. PS were administered as a monotherapy, adjunct therapy, in oral or intravenous preparation and in comparison with a placebo or an active therapy. Most effects were measured in the short term (up to four weeks). Thirteen trials had some usable data for meta-analyses. Three trials (62 participants) demonstrated that oral PS, as a monotherapy, significantly reduced short term depressive symptoms in comparison with placebo (SMD -0.87, 95% CI -1.40, -0.33, with non-significant heterogeneity. A similar effect was found for fatigue. In the short term PS were acceptable and well tolerated. Tolerance and dependence were under evaluated. No statistically significant difference in depression symptoms was found between modafinil and placebo.

Authors' conclusions

There is some evidence that in the short-term, PS reduce symptoms of depression. Whilst this reduction is statistically significant, the clinical significance is less clear. Larger high quality trials with longer follow-up and evaluation of tolerance and dependence are needed to test the robustness of these findings and, furthermore, to explore which PS may be more beneficial and in which clinical situations they are optimal.

摘要

背景

精神興奮劑使用於憂鬱症

憂鬱症是常見,造成失能,昂貴且常沒被適當治療。中度或重度憂鬱症目前的第一線治療抗憂鬱劑,常面臨一些問題。有研究評估關於精神興奮劑在憂鬱症治療的效果,但這些研究都沒有被系統性的回顧

目標

確定精神興奮劑在治療憂鬱症的效果及評估其相關的副作用

搜尋策略

2006年6月21日我們搜尋了CCDANCTRStudies及CCDANCTRReferences資料庫。Cochrane Central Register of Controlled Trials,MEDLINE,EMBASE,PsycInfo,AMED,CINAHL,Dissertation Abstracts及the National Health Service Research Register都被搜尋

選擇標準

納入關於評估精神興奮劑效果的臨床隨機對照試驗,試驗族群為成年人,男女不拘,診斷罹患憂鬱症者

資料收集與分析

兩位回顧作者獨立提取資料且評估試驗的品質,試驗有可比較特性時,會考慮做統合分析。首要結果是憂鬱症狀,以連續的結果來看,使用標準平均差異(SMD),獲以二分法測量臨床反應,以95%信賴區間(CI)來計算勝算比(OR)

主要結論

找到24個隨機對照試驗,整體試驗的品質是不佳的,有五個藥物被評估:dexamphetamine,methylphenidate,methylamphetamine,pemoline及modafinil。modafinil被分開評估,因為它的藥理作用和其他的精神興奮劑是不同的。精神興奮劑被當作單一治療藥物或加成治療藥物,以口服或靜脈注射,來跟安慰劑或其他有效的療法相比較。大部分的效果是測量短期的(最多至四週),13個試驗中有一些資料可用來做統合分析。3個試驗(62位試驗者)沒有明顯異質性,呈現口服的精神興奮劑,作為一個單一治療藥物跟安慰劑相比,明顯的減少短期的憂鬱症狀(標準平均差異SMD −0.87,95%信賴區間CI −1.40至−0.33),對於疲勞發現具有類似的效果,短期精神興奮劑的使用是被接受的且具良好的耐受性。modafinil及安慰劑之間對於憂鬱的症狀並沒有統計上明顯的差異

作者結論

有一些證據顯示短期精神興奮劑可以減少憂鬱症的症狀,雖然這減少有統計意義,但是臨床意義是不太清楚。較大的高品質試驗,有較長的後續追蹤,和評估耐受性和依賴是需要的,用來測試這些研究結果的強度,此外,探索精神興奮劑可能會更有其效果,並在臨床狀況下,他們是合適的選擇

翻譯人

本摘要由彰化基督教醫院許文郁翻譯

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

總結

精神興奮劑使用於憂鬱症。憂鬱症常見且常沒被適當治療。目前的第一線治療中度或重度憂鬱症的藥物是抗憂鬱劑,但在他們的使用仍有一些困境。這篇回顧從精神興奮劑治療憂鬱症效果的隨機對照試驗,來評估證據。共找到24個隨機對照試驗,其中14個的資料可拿來做統合分析。有五個藥物被評估:dexamphetamine,methylphenidate,methylamphetamine,pemoline及modafinil。modafinil被分開評估,因為它的藥理作用和其他的精神興奮劑是不一樣的。3個小型試驗,包括62位試驗者,呈現短期(最多至四週)口服的精神興奮劑跟安慰劑比較,顯著的減少憂鬱症狀,然而整體試驗品質不佳,限制了這些發現結果的可信度。2個試驗包括411位參與個案,比較modafinil及安慰劑分別加到抗憂鬱劑治療6至8週,發現減少憂鬱症狀並沒有明顯差異。1個小型試驗包括50位參與個案,比較modafinil及安慰劑,12週治療後,也顯示在減少憂鬱症狀並沒有明顯的差異。沒有試驗檢驗精神興奮劑的長期效果,進一步長期追蹤設計完善的試驗是必須的,以發現精神興奮劑在治療憂鬱症的更多效用及精神興奮劑是否在憂鬱症中的特定族群更有其療效

摘要

精神兴奋剂治疗抑郁症

研究背景

抑郁症是一种常见的疾病,损害人的正常功能、疾病负担大且缺乏足够的治疗。目前,中度或重度抑郁症的一线治疗药物抗抑郁剂,在使用上存在一些问题。已有大量研究评估了精神兴奋剂对抑郁症的疗效,但仍缺乏系统评价。

研究目的

确定精神兴奋剂治疗抑郁症的效果,并评价其不良反应。

检索策略

检索了CCDANCTR-Studies 及CCDANCTR-References数据库,检索截至2006年6月21日。同时还检索了Cochrane Central Register of Controlled Trials,MEDLINE,EMBASE,PsycInfo,AMED,CINAHL,Dissertation Abstracts以及National Health Service Research Register。

标准/纳入排除标准

纳入评价精神兴奋剂疗效的随机对照试验,试验对象为诊断为抑郁症的男女性成年人。

数据收集与分析

两位评价者独立提取数据并评价文献质量。对主要特征可比的研究进行Meta-分析。主要结局指标是抑郁症状,对连续性变量结果,计算SMD(标准化均数差);对于临床反应等二分类变量,计算比值比(OR)及其95%可信区间。

主要结果

纳入24个随机对照试验,但总体质量较低。共评价了5种药物: dexamphetamine(右旋安非他明), methylphenidate(哌醋甲酯),methylamphetamine(甲基苯丙胺), pemoline(匹莫林)和modafinil(莫达非尼)。因为modafinil的药理作用不同于其他几种精神兴奋剂,故对其单独进行评价。在这些试验中,精神兴奋剂或单独使用或联合用药,或口服或静脉注射,或与安慰剂对照或与其他疗法比较。大多数试验测量的是短期效果(最多4周)。其中13个试验可做Meta-分析。3个试验(n=62)的结果显示,与安慰剂相比,单独口服精神兴奋剂可明显减少短期的抑郁症状(SMD= −0.87,95%CI: −1.40∼−0.33 ),且试验组间无明显的异质性。对于疲劳这一结局指标,也发现类似的效果。短期使用精神兴奋剂是可接受的且有良好的耐受性。其耐受性和依赖性仍在评价中。Modafinil与安慰剂相比,对于抑郁症状的改善并无差异。

作者结论

有证据显示短期使用精神兴奋剂可以减少抑郁症状。不过尽管这种效果有统计学上的意义,但其临床意义却不甚明了。需要开展更大样本、更长随访时间和更高质量的研究,并评价其耐受性和依赖性,从而验证本次研究结果的证据强度,并进一步探讨哪种精神兴奋剂可能会有更好的效果,以及在不同临床状况下的适用性。

Plain language summary

Psychostimulants for depression

Depression is common and under-treated. The current first-line drug treatment for moderate or severe depression is antidepressants, but there are problems with their use. This review evaluated the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of psychostimulants (PS) in the treatment of depression. Twenty-four RCTs were identified, of which 14 had data for meta-analysis. Five drugs were evaluated, including dexamphetamine, methylphenidate, methylamphetamine, pemoline and modafinil. Modafinil was evaluated separately as its pharmacology differs from other PS. Three small trials of PS involving a total of 62 participants indicated that oral treatment with PS in the short term (up to four weeks) significantly reduced depressive symptoms when compared with placebo, however, the overall quality of the trials was poor, limiting confidence in the findings. Two trials involving 411 participants compared modafinil against placebo when combined with antidepressant treatment at 6-8 weeks, and showed a non-significant difference in reducing depression symptoms. One small trial of 50 participants compared oral modafinil against placebo after 12 weeks of treatment, and also showed a non-significant difference in reducing depression symptoms. No trials examined the longer-term effect of PS. Further well conducted trials with long term follow-up are required to find out which PS may be more effective in the treatment of depression, and whether PS are more effective in certain subgroups of depressed patients.

概要

精神兴奋剂治疗抑郁症

抑郁症是常见的,且缺乏足够治疗的疾病。目前用于治疗中度和重度抑郁症的一线药物是抗抑郁剂,但是这些药物的使用存在一些问题。本文评价了精神兴奋剂治疗抑郁症的随机对照试验。共找到24个随机对照试验,其中14个可进行Meta-分析。这些试验评价了5种药物,包括dexamphetamine(右旋安非他明),methylphenidate(哌醋甲酯),methylamphetamine(甲基苯丙胺),pemoline(匹莫林)和modafinil(莫达非尼)。因为modafinil的药理作用不同于其他几种精神兴奋剂,所以单独进行评估。3个小样本试验(共包含62名研究对象)的结果显示,与安慰剂相比,短期(最多4周)口服精神兴奋剂明显减少了抑郁症状。但这些试验的总体质量较低,限制了结果的可信度。两个试验(n=411)比较了modafinil与安慰剂分别与抗抑郁剂联用6–8周的效果,结果发现两者对抑郁症状的控制效果没有显著差异。一个包含50名受试者的小型试验,比较了口服modafinil与安慰剂治疗12周后,也未发现减少抑郁症状的疗效差异。尚无试验研究精神兴奋剂的长期效果。需要进一步开展设计完善的长期随访试验,以发现哪种精神兴奋剂治疗抑郁症更有效,以及精神兴奋剂是否在特殊类型的抑郁患者中更有效。

翻译注解

本摘要由重庆医科大学中国循证卫生保健协作网(China Effective Health Care Network)翻译。

Translated by: China Effective Health Care Network

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