Treatment for amphetamine withdrawal

 

Abstract

Background

Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different.

Objectives

To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes.

Search methods

MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles.

Selection criteria

All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms.

Data collection and analysis

Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes.

Main results

Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear.  One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms.  

Authors' conclusions

No medication is effective for treatment of amphetamine withdrawal. Amineptine showed reduction in discontinuation rates and improvement in clinical presentation compared to placebo, but had no effect on reducing withdrawal symptoms or craving. In spite of these limited benefits, amineptine is not available for use due to concerns over abuse liability when using the drug. The benefits of mirtazapine as a withdrawal agent are less clear based on findings from two randomised controlled trials: one report showed improvements in amphetamine withdrawal symptoms over placebo; a second report showed no differences in withdrawal symptoms compared to placebo.  Further potential treatment studies should examine medications that increase central nervous system activity involving dopamine, norepinephrine and/or serotonin neurotransmitters, including mirtazapine.

 

Plain language summary

Treatment for amphetamine withdrawal

Symptoms of amphetamine withdrawal during the initial days of abstinence from chronic amphetamine use can prompt individuals to return to regular drug use. No medications demonstrate significant effects over placebo in reducing symptoms of acute amphetamine withdrawal.

Amphetamines can make people feel more alert, and are prescribed for problems like depression and attention deficit order. Amphetamines can produce euphoria, and so are manufactured for recreational use. Ongoing use can lead to dependence, which can be as hard to recover from as dependence on heroin or cocaine.  The only randomized trials of amphetamine withdrawal agents have been of antidepressant drugs (amineptine and mirtazapine).   Amineptine was found to have limited benefits, showing improvement only on some subjective effects but is no longer on the market because of concerns over its abuse liability. The benefits of mirtazapine have been less clear based on two randomised controlled trials, with one showing improvements in amphetamine withdrawal symptoms and the other showing no differences in withdrawal outcomes when compared to placebo.  More research is needed.

 

摘要

背景

安非他命戒斷之治療

探討安治療非他命戒斷的研究不多，雖然這在安非他命使用者間是一個常見的問題。其症狀，尤其是強烈的渴求，也許是導致安非他命使用者復發的一個重要因素。臨床上的做法，通常以用於古柯鹼戒斷的藥物來管理安非他命戒斷，雖然這兩種非法藥物的藥物學及藥物動力學的特性不同。

目標

評估單一的藥理或合併心理社會治療對於安非他命戒斷的中斷率，整體狀態，戒斷症狀，渴求感與其他結果的效果。

搜尋策略

MEDLINE (1966 – 2008年)，CINAHL (1982 – 2008年)，PsycINFO (1806 – 2008年)，CENTRAL (考科藍圖書館，2008年，第2期)，取得文章的參考文獻。

選擇標準

所有相關的隨機對照試驗(randomised controlled trials (RCTs))與對照臨床試驗(controlled clinical trials (CCTs))。研究對象為經由任何一套標準診斷之安非他命戒斷的病患。評估單一或合併任何類型的生物與心理治療。考量各種結果，例如，有療效反應的人數，分數變化。

資料收集與分析

兩名作者分別評估並摘錄資料。從意圖治療分析中摘錄資料。使用相對風險(Relative Risk (RR))與95%信賴區間(95% confidence interval (95% CI))來評估類別變項的結果。使用加權平均差(Weighted Mean Difference (WMD))與95% CI來評估連續變項的結果。

主要結論

四篇隨機對照試驗(包含125名研究對象)符合納入標準。兩篇研究發現，相較於安慰劑，amineptine可以顯著減少中斷率並改善整體的臨床表現，但不會減少戒斷症狀或渴求感。Mirtazapine相較於安慰劑對於減少安非他命戒斷症狀的好處並不清楚。一篇研究認為mirtazapine也許會減少因安非他命戒斷造成的過度反應與焦慮症狀。最近的一篇研究沒有發現mirtazapine相較於安慰劑對於持續治療或安非他命戒斷症狀的任何效益。

作者結論

沒有藥物對於治療安非他命戒斷是有效的。顯示相較於安慰劑，amineptine會減少中斷率並改善臨床表現，但對於減少戒斷症狀或渴求感則沒有效果。儘管這些有限的效益，但amineptine並不適合使用，因為考量使用這類藥物時容易有濫用的情形。依據兩篇隨機對照試驗的結果，mirtazapine作為戒斷劑的效益並不清楚：一篇報告顯示，相較於安慰劑，mirtazapine可以改善安非他命的戒斷症狀；第二篇報告顯示，mirtazapine與安慰劑沒有差異。進一步可能治療的研究應評估增加中樞神經系統活動的藥物，包含dopamine，norepinephrine與/或serotonin neurotransmitters，包括mirtazapine。

翻譯人

本摘要由高雄榮民總醫院金沁琳翻譯。

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

總結

在禁止長期安非他命使用的剛開始幾天，安非他命戒斷症狀會造成個人重返常規的藥物使用。沒有藥物證實比安慰劑對於減少急性安非他命戒斷症狀有顯著效果。 安非他命會使人較為警覺，並開立處方給予像憂鬱症與注意力缺乏症的問題患者。安非他命可產生欣快感，因此也被製造為娛樂的用途。持續使用會造成依賴性，其難以康復如海洛因或古柯鹼依賴性。安非他命戒斷製劑的隨機試驗只有抗憂鬱藥物(amineptine與mirtazapine)。發現amineptine具有限的效益，顯示只改善某些主觀的效果，但不再需要這種藥物，因為考量到容易有濫用的情形。根據兩篇隨機對照試驗的結果，mirtazapine的效益並不清楚，一篇顯示對於安非他命戒斷症狀有改善，而另一篇顯示相較於安慰劑對於戒斷症狀沒有差異。需要更多的研究。