Efficacy of mood stabilisers in the treatment of impulsive or repetitive aggression: systematic review and meta-analysis

Abstract

Background: Individuals with repetitive or impulsive aggression in the absence of other disorders may be diagnosed with intermittent explosive disorder according to DSM-IV, but no such diagnostic category exists in ICD-10. Mood stabilisers are often used off-license for the treatment of aggression associated with a variety of psychiatric conditions, but their efficacy in these and in idiopathic aggression is not known.

Aims: To summarise and evaluate the evidence for the efficacy of mood stabilisers (anticonvulsants/lithium) in the treatment of impulsive or repetitive aggression in adults.

Method: A meta-analysis of randomised controlled trials that compared a mood stabiliser with placebo in adults without intellectual disability, organic brain disorder or psychotic illness, identified as exhibiting repetitive or impulsive aggression.

Results: Ten eligible trials (489 participants) were identified A pooled analysis showed an overall significant reduction in the frequency/severity of aggressive behaviour (standardised mean difference (SMD) = -1.02, 95% CI -1.54 to -0.50), although heterogeneity was high (I(2) = 84.7%). When analysed by drug type, significant effects were found in the pooled analysis of three phenytoin trials (SMD = -1.34, 95% CI -2.16 to -0.52), one lithium trial (SMD = -0.81, 95% CI -1.35 to -0.28), and two oxcarbazepine/carbamazepine trials (SMD = -1.20, 95% CI -1.83 to -0.56). However, when the results of only those studies that had a low risk of bias were pooled (347 participants), there was no significant reduction in aggression (SMD = -0.28, 95% CI -0.73 to 0.17, I(2) = 71.4%).

Conclusions: There is evidence that mood stabilisers as a group are significantly better than placebo in reducing aggressive behaviour, but not all mood stabilisers appear to share this effect. There is evidence of efficacy for carbamazepine/oxcarbazepine, phenytoin and lithium. Many studies, however, were at risk of bias and so further randomised controlled trials are recommended.