Abstracts

Rationale: Focal onset epilepsy impairs patient quality of life via seizures and medication side effects. Patients are initially or quickly become refractory to anti-epileptic drugs (AEDs) that reduce frequency, but rarely eliminate seizures, and impart significant side effects. Thus, improvement in quality of life (treatment utility) stems from a reduction of seizure frequency and side effects. Transcranial Magnetic Stimulation (TMS) directed at the seizure onset zone, as an adjunct to AEDs, has recently emerged as a non-invasive treatment to reduce seizure frequency with a favorable side effect profile. Here, we employ a meta-analytic strategy to determine the relative efficacy, safety, and utility of AEDs versus adjunctive TMS for treatment of focal onset refractory epilepsy.  Methods: A PubMed/Medline search was performed for English language clinical studies of refractory focal onset epilepsy patients initiating a new anticonvulsant or adjunctive TMS. Inclusion criteria were: clinical studies of more than one patient, patients above 16 years of age, refractory to at least one AED, and reported baseline and post-treatment seizure frequency. Medication side effects and complications of TMS were collected when reported. Efficacy and side effect data from AED (n = 29) and TMS (n = 7) studies meeting inclusion criteria were pooled. Placebo patients represent either sham TMS or inactive pills. Published utility values for seizure reduction and side effects as well as pooled efficacy data were used as parameters in a decision-analysis model comparing utility of AEDs, TMS, and placebo.  Results: A total of 6975 patients were included in the analysis, representing 5487 AEDs, 193 TMS, and 1295 placebo patients. Patient groups were similar in sex and time since epilepsy diagnosis, but varied in age, seizure frequency, and length of medication/TMS trial (p < 0.001). TMS patients had higher baseline seizure frequency and shorter trial duration. With regards to seizure frequency; AEDs, TMS, and placebo demonstrated 48.4% (SD 20.4), 34.4% (SD 39.9), and 26.3% (SD 11.4) reductions, respectively. On average, AED patients experienced 2.1 side effect events, TMS 0.12, and placebo 1.0 during the treatment period. The overall utility improvement was 32.4 % (SD 1.3), 33.0 % (SD 0.6), and 26.3% (0.1 SD), respectively amongst the groups (F = 1936, p < 0.001). Conclusions: For refractory focal epilepsy patients, anti-epileptic drugs maintain only a weak non-significant advantage in reducing seizure frequency over adjunctive TMS. However, given significant morbidity imparted by AEDs from increased side effects, our model predicts adjunctive TMS imparts superior improvement in quality of life (overall utility), through a moderate reduction of seizure frequency with a dominant contribution from less frequent side effects. Given these data, clinicians may accept a lower threshold for seizure reduction efficacy for side-effect sparing therapies. Our studies emphasize continued clinical investigation of TMS for focal epilepsy. Further, we support the application of utility analyses in the prospective clinical evaluation of medical and surgical therapies for epilepsy patients. Funding: None