Adjunctive brivaracetam in focal and generalized epilepsies: A single-center open-label prospective study in patients with psychiatric comorbidities and intellectual disability.

Clinical studies suggest that the antiepileptic drug (AED) brivaracetam (BRV) is associated with fewer behavioral and psychiatric adverse events (AEs) compared with levetiracetam (LEV) in treating epilepsy. There are, however, few comparative studies of treatment-emergent AEs between patients on BRV with preexisting psychiatric or behavioral comorbidities to those without. Our study compared longer-term tolerability over a 26-month period between these patient groups and assessed the overall efficacy of BRV as add-on therapy. Patients with intellectual disabilities in whom the prevalence of epilepsy is higher, are often excluded from randomized controlled trials, and our study further assessed comparative effectiveness between this patient group and those with normal range intellect. We collected prospective data on 134 patients prescribed add-on BRV for epilepsy at a tertiary UK center over a 26-month period. All patients had previously received LEV. Sixty-three patients were on LEV at the start of the data collection period. Levetiracetam was withdrawn and switched to BRV in 39 patients because of inefficacy and 24 patients because of behavioral or psychiatric side effects. Seventy-three patients (54%) had a preexisting psychiatric or behavioral disorder compared with 64 patients (46%) without. The retention rate at last follow-up [mean: 11 months (0.5-26 months)] was 60% in the psychiatric/behavioral disorders group versus 67% in those without (p = 0.68). Forty-one patients had diagnosed intellectual disabilities. The retention rate was 66% in this group versus 62% in patients without intellectual disabilities (p = 0.36). The commonest treatment-emergent AEs were somnolence (26%), aggression (23%), and depression (9%). There were similar frequencies reported for these specific events across the groups. The proportion with a 50% responder rate was 29% in patients with focal epilepsy and 47% in patients with generalized and combined focal and generalized epilepsies. However, fifteen patients (11%) reported increased seizure activity leading to withdrawal of treatment. This study showed evidence that BRV may be an effective adjunctive therapy in patients with drug-resistant focal or generalized epilepsies whose seizures have previously not responded or tolerated LEV therapy. We demonstrated a higher incidence of treatment-emergent AEs leading to lower retention rates compared with previous studies across all patient groups. There were, however, no significant differences in tolerability between patients with preexisting psychiatric or behavioral comorbidities, or intellectual disability to those without.