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Meta-Analysis
. 2010 Feb 17;2010(2):CD003499.
doi: 10.1002/14651858.CD003499.pub3.

Antiepileptics for aggression and associated impulsivity

Nick Huband  1 , Michael Ferriter, Rajan Nathan, Hannah Jones
Affiliations
Meta-Analysis

Antiepileptics for aggression and associated impulsivity

Nick Huband et al. Cochrane Database Syst Rev. .

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 strategy: 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.

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 1 Overall clinical response: numbers classed as 'responders', at endpoint (8 weeks).
1.2
1.2. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 2 Adverse events, any.
1.3
1.3. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 3 Adverse events, rash.
1.4
1.4. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 4 Adverse events, headache.
1.5
1.5. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 5 Adverse events, weight gain.
1.6
1.6. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 6 Adverse events, increased appetite.
1.7
1.7. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 7 Non‐compliance: leaving the study early, any reason.
1.8
1.8. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 8 Aggression: number improved as > 69% reduction on MOAS + SCL‐90 'irritability', at 6 wks.
1.9
1.9. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 9 Adverse events, nausea.
1.10
1.10. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 10 Adverse events, somnolence.
1.11
1.11. Analysis
Comparison 1 Valproate/divalproex versus placebo, Outcome 11 Non‐compliance: leaving the study early, any reason; Cluster B PD subgroup.
2.1
2.1. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 1 Adverse events, any.
2.2
2.2. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 2 Adverse events, rash/dermatitis.
2.3
2.3. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 3 Adverse events, headache.
2.4
2.4. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 4 Adverse events, dizziness.
2.5
2.5. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 5 Adverse events, stomach ache.
2.6
2.6. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 6 Adverse events, weight loss.
2.7
2.7. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 7 Adverse events, weight gain.
2.8
2.8. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 8 Non‐compliance: leaving the study early, any reason.
2.9
2.9. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 9 Aggression (self‐reported): number with any aggression to others/objects, over last 3 wks of intervention.
2.10
2.10. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 10 Aggression (self‐reported): number with any aggression to others/objects/self, over last 3 wks of intervention.
2.11
2.11. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 11 Adverse events, leucopenia.
2.12
2.12. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 12 Anger: more than one angry outburst, over 6 weeks.
2.13
2.13. Analysis
Comparison 2 Carbamazepine versus placebo, Outcome 13 Anger: any angry outburst, over 6 weeks.
3.1
3.1. Analysis
Comparison 3 Phenytoin/diphenylhydantoin versus placebo, Outcome 1 Non‐compliance: leaving the study early, any reason.
3.2
3.2. Analysis
Comparison 3 Phenytoin/diphenylhydantoin versus placebo, Outcome 2 Adverse events, nausea.
4.1
4.1. Analysis
Comparison 4 Levetiracetam versus placebo, Outcome 1 Non‐compliance: leaving the study early (before 4 weeks), any reason.
4.2
4.2. Analysis
Comparison 4 Levetiracetam versus placebo, Outcome 2 Adverse events, sedation.
4.3
4.3. Analysis
Comparison 4 Levetiracetam versus placebo, Outcome 3 Adverse events, dizziness.
4.4
4.4. Analysis
Comparison 4 Levetiracetam versus placebo, Outcome 4 Adverse events, headache.
5.1
5.1. Analysis
Comparison 5 Oxcarbazepine versus placebo, Outcome 1 Aggression (self‐reported): OAS‐M‐revised, number of responders as > 49% reduction in Global Overt Aggression score, at 10 wks.
5.2
5.2. Analysis
Comparison 5 Oxcarbazepine versus placebo, Outcome 2 Non‐compliance: leaving the study early, any reason.
5.3
5.3. Analysis
Comparison 5 Oxcarbazepine versus placebo, Outcome 3 Non‐compliance: leaving the study early, due to adverse events.
5.4
5.4. Analysis
Comparison 5 Oxcarbazepine versus placebo, Outcome 4 Non‐compliance: leaving the study early, due to ineffectiveness.
6.1
6.1. Analysis
Comparison 6 Any epileptic drug versus placebo, Outcome 1 Non‐compliance: leaving the study early, any reason.
6.2
6.2. Analysis
Comparison 6 Any epileptic drug versus placebo, Outcome 2 Adverse events, any.
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