Abstracts

Bromides were a mainstay of seizure therapy from their discovery in 1857 until manufacture stopped in 1992, but long-term studies of its use are lacking. We examined the long-term tolerability and safety of bromides for patients prospectively enrolled in a long-term study. Subjects were patients with seizures that did not respond to available therapy or who were taking bromides in 1992 when its commercial manufacture was stopped. Triple salts of bromides (906 mg/5 ml) were administered in a slowly escalating dose and patients were evaluated every 4-6 months, including bromide levels. Adverse events (AEs) and seizure frequency were collected as spontaneously reported. Seizure type and frequency were collected posthoc. Seventeen patients were enrolled. Mean age was 26 years (range 10-52), 12 were men, and 12 were cognitively impaired. Generalized seizures were present in 10 (7 with multiple generalized types). Etiology was cryptogenic in 14. Mean bromide dose was 10 cc/day (range 2.5-25). Mean serum level was143 mg/dl at steady state, 167 at the maximum dose and 74 at the minimum dose. Mean duration of therapy was 3.2 years (range 0.08-9.75), for a total of 51 patient-years. 152 adverse events occurred in 16 subjects, but only 44 were considered drug related. Five subjects took bromides 2 months or less. All drug-related AEs were mild or moderate. The most common AEs were acne (14), lethargy (12), ataxia (4), difficulty concentrating or confusion (3), and behavioral changes (2). Six subjects reported lack of improvement but all who received it for [gt]2 months had reduction of seizure frequency. Median seizure frequency was reduced from 40 to 6 seizures/month (p= 0.04) with median reduction of 75%. Most subjects were withdrawn because seizures did not improve sufficiently, side effects were intolerable, or it was ineffective. Bromides are commonly associated with acne, lethargy and ataxia. Refractory patients who can tolerate the side effects at initiation of therapy gain long-term effectiveness and may find the side effects acceptable later in therapy. Bromides remain a useful antiepileptic drug.