Management and monitoring of patients treated with zonisamide: the OZONE study

Abstract

To characterise patients treated with zonisamide in everyday practice and describe the effectiveness and tolerability of treatment. Methods. This was an observational, longitudinal, naturalistic study, conducted by neurologists in France. Patients who had started zonisamide treatment at least three months prior to inclusion were eligible. Data were collected at routine consultations at inclusion (Visit 1) and three to six months later (Visit 2). At Visit 1, investigators documented epilepsy-related variables based on patient records before initiation of zonisamide and at inclusion. At Visit 2, the investigators re-evaluated seizure activity and rated effectiveness. Adverse events were also documented. Results. A total of 428 patients were included in the study based on evaluation by 132 neurologists. Zonisamide was initiated at a daily dose of 50 mg and 25 mg in 61% and 31.8% of patients, respectively. The median maintenance dose was 300 mg/day. Prior to initiation of zonisamide, the mean seizure frequency was 16.0 seizures/month. This was reduced to 8.7 seizures/month at Visit 1 and to 7.1 seizures/month at Visit 2. The response rate and proportion of seizure-free patients was 61.9 and 31.1% at Visit 1 and 65.9 and 25.6% at Visit 2, respectively. The frequency of seizures at Visit 2 decreased significantly (p<0.05) for all seizure type subgroups, except for simple partial seizures. Responder rates were >60% for all analysed subgroups. The proportion of seizure-free patients was significantly higher in patients receiving bitherapy, compared to the others (p=0.007). The most frequently reported adverse event was somnolence (5.1%); three serious adverse events were reported. Conclusion. In everyday practice, zonisamide is principally used in association with other antiepileptic drugs for the treatment of focal epilepsy in adults. It is effective in improving seizure control and quality of life, and is generally well-tolerated.

Evaluation of safety and efficacy of zonisamide in adult patients with partial, generalized, and combined seizures: an open labeled, noncomparative, observational Indian study

“…The primary outcome of this study was impressive with more than approximately 80% of patients achieving ≥50% reduction in seizure frequency, whereas seizure freedom was achieved in approximately 41% of patients after 24 weeks of zonisamide treatment. The responder rate and proportion of patients who achieved seizure freedom with zonisamide were 40.9% and 15%, respectively, in ZEUS; 12 79% and 34% in ZADE study; 13 65.9% and 25.6% in OZONE study; 14 and 79.7% and 43.6% in ZOOM study. 15 This difference may be attributable to inclusion of patients with less severe and less refractory epilepsies in our study.…”

Mechanisms and Pharmacotherapy for Ethanol-Responsive Movement Disorders

“…Zonisamide has a clear advantage over ethanol in that it has been proved relatively safe, effective, and well-tolerated in long-term treatments as monotherapy or adjunctive therapy (115,116). Additionally, zonisamide has a pharmacokinetic characteristic favorable for clinical use.…”

Anticonvulsant Agents: Zonisamide

“…The results of the pivotal add-on studies are shown in Table 1. Long-term efficacy of ZNS as add-on therapy in adults with focal epilepsy could be documented both in open-label extension studies completing fixed-dose, randomized, double-blind clinical trials (Brodie 2004;Wroe et al 2008) and in several openlabel real-world studies (Dupont et al 2010(Dupont et al , 2013Hamer et al 2016;Helmstaedter et al 2011). In these studies, responder rates and proportions of seizure-free patients were 40.9-44.2% and 15.0-15.9% in the ZEUS study (281 patients, follow-up 19 weeks) (Dupont et al 2010), 79% and 34% in the ZADE study (207 patients, follow-up 4 months) (Helmstaedter et al 2011), 65.9% and 25.6% in the OZONE (Dupont et al 2013), and 79.7% and 43.6% in the ZOOM study (100 patients, follow-up 6 months) (Hamer et al 2016).…”