Psychiatric adverse events during vigabatrin therapy

Objective: To determine the incidence of psychiatric adverse events associa ted with vigabatrin therapy, we reviewed data from US and non-US double-bli nd, 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 adver se event dictionary. Terms for psychiatric events were then combined into c ategories 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 betwe en treatment groups for aggressive reaction, manic symptoms, agitation, emo tional lability, anxiety, or suicide attempt. Although depression and psych osis were typically observed during the first 3 months, most studies were 1 2 to 18 weeks long, so that definitive conclusions could not be reached abo ut timing of events. Psychosis was generally transient and reported to be r esponsive to reduction or discontinuation of vigabatrin or to neuroleptic t reatment. Depression was typically mild. Serious depression, defined as dis continued from the study, hospitalized, or suicide attempt, or coded as psy chotic depression, occurred in only 9 of the 49 vigabatrin-treated patients with depression. Conclusions: Vigabatrin use in treatment-refractory parti al epilepsy is associated with increased occurrence of depression and of ps ychosis, although the frequency of psychosis is apparently lower than previ ously reported. Clinical experience suggests that these adverse events resp ond to reduction of vigabatrin dose or to counteractive psychotropic treatm ent.