Abstracts

RATIONALE: It is sometimes better to introduce new antiepileptic drugs (AEDs), in a limited timeframe utilizing rapid titration while patients are hospitalized, thereby obtaining better seizure control and limiting adverse events (AEs). Zonisamide (ZNS), a new AED, is used in this study. The objective is to better understand the rapid titration within a hospital setting for patients treated with ZNS.
METHODS: Fifty-five adult patients with medically intractable epilepsy, aged 20-91 years (average age 43.5) (24 male, 31 female patients), were admitted to the hospital for the addition of ZNS to obtain better seizure control. The titration schedule was individualized for each patient based on his/her tolerability for the drug, AEs and seizure control. ZNS was started at 100mg/day on day one of the titration. Days to complete titration ranged from 1 to 9 days with the average being 5.8 days. Maximum ZNS doses ranged from 100 to 700mg/day with the average being 350mg/day. Patients were on from 1 to 4 other AEDs. Five patients were on 1 (AED) (9%), 27 on 2 (AEDs) (49%), 16 on 3 (AEDs) (29%) and 4 were on 4 (AEDs) (13%). In-patient ZNS blood levels were available on 28 patients with the average level being 11.7mcg/ml.
RESULTS: Of the 55 patients started on ZNS while in the hospital only three (6%) were discontinued prior to discharge: 1 for a noticeable increase in seizure activity, 1 for confusion, and 1 for a decreased spontaneity and sleepiness. Nine patients (16%) discontinued ZNS prior to or at the first clinic visit. Normal timeframe for first clinic visit after hospitalization was 6-8 weeks. Reasons for discontinuation were: 2 patients with noticeable increase in seizure activity, 2 with tinnitus, 2 with no noticeable improvement in seizures, 1 with active EEG and incontinence, and one with incontinence, vomiting, mood swings and appetite fluctuations. The last patient switched back to her previous AEDs one week after hospital discharge. Twenty-one of the 55 patients (38%) had a greater than or equal to 50% reduction in seizures including 6 patients who were seizure free. Nine patients (16%) had improved seizure control and 6 (11%) had no change. Seven (13%) had a decrease in seizure control including 2 patients who were noncompliant with their medications, and 1 who needed a replacement of the Vagus Nerve Stimulator. Thirty-six patients had blood levels drawn by their first clinic visit. The average level was 21.9mcg/ml, which reflects the average dose of 386mgs of ZNS.
CONCLUSIONS: A rapid titration of Zonisamide in the hospital environment can be achieved safely with minimal adverse effects along with the expectation of significantly improved seizure control.