A 2021 systematic review investigated the efficacy of topiramate as add-on therapy for refractory status epilepticus (RSE) based on studies that report response rate, mortality rate, or long-term outcomes. A total of 8 studies were included, with one being prospectively designed (see Table 1). The majority of studies included a small number of patients (N= 6 to 27) with the largest retrospective study including 106 patients (Fechner et al., Table 2). Studies varied in types of seizures and population characteristics were largely similar. Doses were highly variable with max daily doses ranging from 400-1600 mg while minimum daily dose ranged from 50-400 mg. The response rate, defined as termination in-hospital until 72 hours after administration, varied from 27% to 100% while mortality rate varied from 5.9% to 68%. Long-term positive outcomes such as discharge, return to baseline, or rehabilitation reported to range from 4% and 55%. The only notable adverse event was hyperammonemia that occurred in 35.8% of patients in the study conducted by Fechner et al. While treatment with topiramate for RSE seems effective, yet due to the wide heterogeneity in dosing and patient populations, the optimal treatment regimen cannot be determined. [1]
Another 2021 article discusses their literature review regarding the off-label use of topiramate for RSE and super-refractory status epilepticus (SRSE). Based on their review, there is insufficient data supporting topiramate based on 1 retrospective study and 6 case reports. In neonates and children, topiramate has shown promise in terminating seizures within 24 hours of enteral administration. Varying loading and maintenance doses are reported that include loading dose of 5 mg/kg BID for 2 days leading to maintenance dose of 2.5 mg/kg BID; and lower loading/maintenance dose of 2-3/5-6 mg/kg/day. [2]
In adults, the evidence for the use of topiramate in RSE is conflicting. Some studies have reported successful termination of RSE in over 70% of patients, while others have not observed meaningful efficacy. Fechner et al. evaluated the adjunctive use of topiramate in RSE and found a positive response in 32% of patients. However, hyperammonemia, mild hyperchloremic acidosis, and pancreatitis have been observed as potential side effects. Initial dose ranged from 25-500 mg (median 100 mg) and maintenance dose ranged from 25-900 mg/day (median 400 mg). [2]
The 2019 research paper by Fechner et al. outlined their large retrospective review, as well as a literature review of existing studies. The original retrospective review, conducted utilizing patient data from select German hospitals, reported an initial median oral topiramate dose of 100 mg/day, uptitrated to a median maintenance dose of 400 mg/day. Treatment time with topiramate spanned a median of 12 days. Included patients were diagnosed with RSE or SRSE. Data from 9 previous studies was included in the literature review, most of which were retrospective; this data is summarized in Table 3. The sole prospective study (Asadi-Pooya et al.) is presented in its entirety in Table 4. [3]