Psychiatric adverse events during vigabatrin therapy

Objective: To determine the incidence of psychiatric adverse events associated with vigabatrin therapy, we reviewed data from US and non-US double-blind, placebo-controlled trials of vigabatrin as add-on therapy for treatment-refractory partial epilepsy. Methods: "Verbatim" terms from investigators' reports had been translated into standard "preferred" terms using an adverse event dictionary. Terms for psychiatric events were then combined into categories for analysis of rates during vigabatrin versus placebo treatment. Results: Compared with placebo, vigabatrin subjects had a higher incidence of events coded as depression (12.1% versus 3.5%, p < 0.001) and psychosis (2.5% versus 0.3%, p = 0.028); there were no significant differences between treatment groups for aggressive reaction, manic symptoms, agitation, emotional lability, anxiety, or suicide attempt. Although depression and psychosis were typically observed during the first 3 months, most studies were 12 to 18 weeks long, so that definitive conclusions could not be reached about timing of events. Psychosis was generally transient and reported to be responsive to reduction or discontinuation of vigabatrin or to neuroleptic treatment. Depression was typically mild. Serious depression, defined as discontinued from the study, hospitalized, or suicide attempt, or coded as psychotic depression, occurred in only 9 of the 49 vigabatrin-treated patients with depression. Conclusions: Vigabatrin use in treatment-refractory partial epilepsy is associated with increased occurrence of depression and of psychosis, although the frequency of psychosis is apparently lower than previously reported. Clinical experience suggests that these adverse events respond to reduction of vigabatrin dose or to counteractive psychotropic treatment.