[Paradoxical aggressive reactions to benzodiazepine use: a review].

INTRODUCTION: With growing prescription and availability, benzodiazepine usage in France is on the increase among the general population. Although its anxiolytic action has long been proven, many side effects can be observed. TYPOLOGY AND PREVALENCE: Paradoxical reactions of aggressiveness under benzodiazepines have been discussed in the scientific literature since the 1960s. This term was introduced to describe reactions of agitation and disinhibition occurring during anxiolytic or hypnotic treatment. Physical aggression, rape, impulsive decision-making and violence have been reported, as well as autoaggressiveness and suicide. General population studies indicate a prevalence of these reactions of less than 1%, and meta-analysis has shown that use of benzodiazepines generates aggressiveness more frequently than it reduces it. It has also been shown that long-term memory (anterograde amnesia) can be impaired following the ingestion of a benzodiazepine. RISK FACTORS: Benzodiazepine-linked disinhibition, auto and heteroaggressiveness, anxiety and criminal acts have been associated with various vulnerability factors. Although the risk of these paradoxical reactions depends on the number of such factors present in a single patient, the effects of the type and dose of benzodiazepine on the frequency and the intensity of paradoxical symptoms are not clear. In terms of personality, several studies have demonstrated the role of low-stress control (specifically high-trait anxiety) on aggressiveness under benzodiazepines. Other authors underline the role of borderline personality disorder as a major risk factor predicting paradoxical reactions. Results of a study on borderline patients show a prevalence of benzodiazepine-linked disinhibition of 58%. On a neuropharmacological level, the influence of the GABA system on the serotonin control and the impact of alcohol seem to be established. Benzodiazepines, specifically when associated with alcohol, seem to facilitate GABAergic transmission, which can be at the origin of the disinhibited behaviours that have been reported. DISCUSSION: In 2000, France was the first country in terms of benzodiazepine use 17.4% of the adult population had been prescribed an anxiolytic. Implications for medicolegal and clinical practice are discussed.