Antiepileptics for aggression and associated impulsivity

 

Abstract

Background

Aggression is a major public health issue and is integral to several mental health disorders. Antiepileptic drugs may reduce aggression by acting on the central nervous system to reduce neuronal hyper-excitability associated with aggression.

Objectives

To evaluate the efficacy of antiepileptic drugs in reducing aggression and associated impulsivity.

Search methods

We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, metaRegister of Controlled Trials (mRCT) and ClinicalTrials.gov to April 2009. We also searched Cochrane Schizophrenia Group's register of trials on aggression, National Research Record and handsearched for studies.

Selection criteria

Prospective, placebo-controlled trials of antiepileptic drugs taken regularly by individuals with recurrent aggression to reduce the frequency or intensity of aggressive outbursts.

Data collection and analysis

Three authors independently selected studies and two authors independently extracted data. We calculated standardised mean differences (SMDs), with odds ratios (ORs) for dichotomous data.

Main results

Fourteen studies with data from 672 participants met the inclusion criteria. Five different antiepileptic drugs were examined. Sodium valproate/divalproex was superior to placebo for outpatient men with recurrent impulsive aggression, for impulsively aggressive adults with cluster B personality disorders, and for youths with conduct disorder, but not for children and adolescents with pervasive developmental disorder. Carbamazepine was superior to placebo in reducing acts of self-directed aggression in women with borderline personality disorder, but not in children with conduct disorder. Oxcarbazepine was superior to placebo for verbal aggression and aggression against objects in adult outpatients. Phenytoin was superior to placebo on the frequency of aggressive acts in male prisoners and in outpatient men including those with personality disorder, but not on the frequency of 'behavioral incidents' in delinquent boys.

Authors' conclusions

The authors consider that the body of evidence summarised in this review is insufficient to allow any firm conclusion to be drawn about the use of antiepileptic medication in the treatment of aggression and associated impulsivity. Four antiepileptics (valproate/divalproex, carbamazepine, oxcarbazepine and phenytoin) were effective, compared to placebo, in reducing aggression in at least one study, although for three drugs (valproate, carbamazepine and phenytoin) at least one other study showed no statistically significant difference between treatment and control conditions. Side effects were more commonly noted for the intervention group although adverse effects were not well reported. Absence of information does not necessarily mean that the treatment is safe, nor that the potential gains from the medication necessarily balance the risk of an adverse event occurring. Further research is needed.

 

Plain language summary

Antiepileptic drugs for treating recurrent aggression

Various medicines, which are collectively termed 'antiepileptic drugs', have been used to treat persistent aggression. This review systematically examines the evidence supporting this practice. From the evidence available, we were unable to draw any firm conclusion about using these medicines to treat aggression. Four antiepileptic drugs (valproate/divalproex, carbamazepine, oxcarbazepine and phenytoin) helped to reduce aggression in at least one study. However, for three of these drugs (valproate, carbamazepine and phenytoin) we found at least one other study where there was no significant improvement. Further research is needed to clarify which antiepileptic drugs are effective for whom. Such research is best carried out using carefully designed clinical trials. Such trials need to take account of the type of aggression displayed, the severity of the aggression, and any other disorders experienced by the participants.

 

摘要

背景

以抗癲癇藥物治療攻擊行為及有關衝動

攻擊行為是一個重要的公共衛生問題，而且是不可或缺的幾個精神衛生疾病。抗癲癇藥物可能透過在中樞神經系統的作用，降低與攻擊有關的神經細胞過度興奮，進而減少攻擊行為。

目標

評估抗癲癇藥物對於減少攻擊行為及有關衝動之療效。

搜尋策略

我們搜尋了直到2009年4月份的CENTRAL、MEDLINE、EMBASE、CINAHL、PsycINFO、metaRegister of Controlled Trials (mRCT) ，以及 ClinicalTrials.gov。同時我們也搜尋了Cochrane Schizophrenia Group's register of trials on aggression、National Research Record，並且以人工搜尋研究。

選擇標準

具復發性攻擊行為之個體規律服用抗癲癇藥物以降低攻擊行為爆發之頻率與強度的前瞻性安慰劑對照試驗。

資料收集與分析

由3位作者獨立挑選研究，2位作者獨立擷取數據。我們計算標準平均差 (standardised mean differences，簡稱SMDs) ，二分性 (dichotomous) 數據則附帶勝算比 (odds ratios，簡稱ORs) 。

主要結論

14個研究共計672名受試者符合納入條件。共評估5種抗癲癇藥物。對於復發性衝動攻擊行為的門診男性病患、B型人格異常及衝動攻擊行為的成人、以及有品行疾患的年輕人來說，Sodium valproate/divalproex 的效果優於安慰劑組，不過在廣泛性發展障礙(pervasive developmental disorder)的兒童及青少年身上則非如此。具有邊緣性人格障礙的婦女，Carbamazepine在減少自我導向侵略行為上優於安慰劑組，不過在具有品行疾患的兒童上則非如此。Oxcarbazepine在門診成人病患當中，口頭攻擊和攻擊對象方面效果優於安慰劑組。Phenytoin在降低男囚犯以及具有人格疾患的的門診男性病患攻擊行為頻率方面，效果優於安慰劑組，但是在有違法傾向的男孩身上，其行為事件發生頻率則非如此。

作者結論

作者認為，本篇回顧所摘錄的證據不足以論斷抗癲癇藥物可以用於治療攻擊行為以及有關的衝動。雖然至少有一篇研究顯示valproate, carbamazepine和phenytoin等三種抗癲癇藥物的治療與對照組之間不具有統計顯著差異，但是至少有一篇研究顯示valproate/divalproex, carbamazepine, oxcarbazepine 和phenytoin等四種抗癲癇藥物用於減少攻擊行為方面是比安慰劑組有效。雖然藥品不良反應報導不全，不過介入組發生副作用的情形較為普遍。缺乏相關藥品資訊並不表示治療是安全的，也不表示潛在治療效益與不良事件發生風險可以平衡。因此有必要作進一步的研究。

翻譯人

本摘要由沈文歆翻譯。

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

總結

以抗癲癇藥物治療攻擊行為及有關衝動: 許多通稱為抗癲癇藥物的藥品被用來治療頑固型的攻擊行為。此篇系統性文獻回顧檢驗支持此一作法的證據。從可得的證據中，我們無法作出任何關於使用這些藥物治療攻擊行為肯定的結論。但是至少有一項研究顯示valproate/divalproex, carbamazepine, oxcarbazepine 和phenytoin等四種抗癲癇藥物有助於減少攻擊行為。然而又至少有一項研究顯示valproate, carbamazepine和phenytoin等三種抗癲癇藥物並不具有顯著改善效果。因此需要進一步的研究釐清哪一種抗癲癇藥物對哪一種人有效。此類研究最好以謹慎的研究設計來進行。這樣的試驗應該要考慮到所展現的攻擊行為的種類、攻擊的嚴重性以及受試者曾經罹患過的疾病。