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

Abstract

BackgroundIndividuals 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.AimsTo summarise and evaluate the evidence for the efficacy of mood stabilisers (anticonvulsants/lithium) in the treatment of impulsive or repetitive aggression in adults.MethodA 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.ResultsTen 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 (I2 = 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, I2 = 71.4%).ConclusionsThere 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.