Antiepileptics for aggression and associated impulsivity.
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.


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


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.


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


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


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.


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.
Huband
Nick
N
Section of Forensic Mental Health, Institute of Mental Health, Nottinghamshire Healthcare Trust, Room B06, The Gateway Building, University of Nottingham, Innovation Park, Triumph Road, Nottingham, UK, NG7 2TU.
Ferriter
Michael
M
Nathan
Rajan
R
Jones
Hannah
H
D000293:Adolescent; D000328:Adult; D000374:Aggression / Q000187:drug effects* / Q000523:psychology; D000786:Anger / Q000187:drug effects; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D000987:Antisocial Personality Disorder / Q000188:drug therapy*; D002648:Child; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000188:drug therapy*; D005260:Female; D006791:Hostility; D006801:Humans; D008297:Male; D055118:Medication Adherence; D016032:Randomized Controlled Trials as Topic
D000927:Anticonvulsants