Efficacy Of Zonisamide Research Articles

Investigation of the Efficacy of Zonisamide in Alcohol Induced Hepatotoxicity

Subject: This research aims to evaluate the histological changes in liver tissue induced by alcohol consumption and to assess the effectiveness of zonisamide in treating alcohol-related hepatotoxicity. Materials and Methods: The study utilized 40 adult Wistar albino rats, divided into four groups: a control (sham), an ethanol group, a zonisamide group, and a combination of ethanol and zonisamide (ethanol+zonisamide). Each group underwent a four-day binge drinking protocol to mimic excessive alcohol intake observed in humans. Zonisamide was administered at a dose of 100 mg/kg daily. Post-treatment, the liver tissues were collected, stained with hematoxylin and eosin, and examined for histopathological changes. Results: The control and zonisamide-only groups showed no abnormal liver or vascular alterations, indicating zonisamide's safety. In contrast, the ethanol group displayed significant liver damage, including vascular dilatation, congestion, and extensive cellular degeneration. Conversely, the ethanol+zonisamide group exhibited substantial histological improvements with noticeable reductions in vascular impairments and signs of hepatocyte regeneration, suggesting that zonisamide mitigates the detrimental effects of alcohol on the liver. Conclusion: The study concludes that zonisamide has a protective effect against alcohol-induced liver damage. It appears to preserve the structural integrity of hepatocytes and supports cellular survival, potentially through its anti-inflammatory and antioxidant properties. These promising results advocate for further exploration of zonisamide as a therapeutic option for managing liver injuries associated with alcohol abuse. This study contributes significant insights into the therapeutic potential of zonisamide, encouraging more comprehensive investigations into its clinical applications in hepatology. Keywords: Alcohol, Zonisamide, Hepatotoxicity

Retracted: Zonisamide's Efficacy and Safety on Parkinson's Disease and Dementia with Lewy Bodies: A Meta-Analysis and Systematic Review.

[This retracts the article DOI: 10.1155/2022/4817488.].

Zonisamide: A Comprehensive, Updated Review for the Clinician.

Zonisamide (ZNS) was first approved in the United States in 2000 for the adjunctive treatment of patients aged 16 years or older with partial (focal) seizures. Although ZNS has been proven to treat multiple seizure types, it has been largely underutilized in US clinical practice. Published literature demonstrated that antiseizure medications (ASMs) acting on Na+ and Ca2+ channels may add beneficial effects in many seizure types by reducing seizure frequency and leading to overall improvements. In addition, effects of ZNS may lead to clinical improvements in Parkinson disease, alcohol and sleep disorders, pain, and migraine. ZNS is available in multiple formulations and is a safe and effective, broad spectrum ASM. The purpose of this review was to provide an update to what is known about the efficacy of ZNS and where it shows benefits in the treatment of patients with epilepsy and other CNS disorders through its many unique mechanisms of action.

Zonisamide for the Efficacy of Sleep Abnormality in Parkinson's Disease (ZEAL Study): A Protocol for Randomized Controlled Trials

Background: Sleep disorders are one of the most frequent non-motor symptoms of Parkinson's disease (PD), and the efficacy of dopaminergic agents remains controversial. Clinical randomized control trials for the treatment of sleep disorders in PD are limited. Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) improved motor symptoms and wearing-off in patients with PD. Patients with PD were reported to have dream-enacting behavior that was resolved after treatment with zonisamide. This study aimed to verify the safety and efficacy of zonisamide for sleep disorders and rapid eye movement (REM) sleep behavioral disorders using a mobile two-channel electroencephalography (EEG)/electrooculography (EOG) recording system.Methods and Analysis: The present study is a randomized placebo-controlled trial to determine the efficacy of zonisamide for sleep disorders in patients with PD. This study was designed to be single-blind, but the subject allocation is randomized by an independent allocation manager via computer-generated block randomization. The subjects in the treatment group took zonisamide (25 mg per day) before bedtime for 28 days. The sleep index is analyzed using a portable EEG/EOG recording system collected on two consecutive nights within 7 days prior to the intervention and reobtained on one night within 2 days after the 28-day administration of zonisamide. The amount of change in sleep efficiency before and after the 28-day administration will be compared between the zonisamide treatment group and placebo group concerning the primary endpoint. As for the secondary endpoint, the change in the ratio of other sleep parameters, including REM sleep without atonia, or sleep architecture will be evaluated.Ethics and Dissemination: The protocol was approved by the Nara Medical University Certified Review Board (CRB5200002). The trial was notified and registered with the Japan Registry of Clinical Trials (jRCTs051200160). Written informed consent will be obtained from every participant using informed consent approved by the CRB. The results of this trial will be disseminated through peer-reviewed scientific journals.

Efficacy, tolerability, and safety of zonisamide in children with epileptic spasms: A systematic review and meta-analysis.

Background: Valproate, levetiracetam, benzodiazepines, and topiramate are antiseizure medications (ASMs) considered to have definite efficacy in reducing the frequency of epileptic spasm frequency, apart from ketogenic dietary therapies. Although zonisamide has also been shown to have efficacy as second-line ASM for epileptic spasms, various studies have conflicting results in literature. This systematic review aims to summarize clinical studies regarding the efficacy of zonisamide for epileptic spasms. Methods: We conducted a systematic literature search collating all available literature. The primary objective was to determine efficacy in terms of proportion with complete spasm resolution, we also intended to determine proportion with at least 50% spasm reduction, hypsarrhythmia resolution, and nature/frequency of adverse effects. All prospective/retrospective, controlled/uncontrolled studies describing the use of zonisamide with epileptic spasms were included in the qualitative review excluding case reports, but for metanalysis pertaining to key outcomes, we included studies with at least 10 participants. Results: A total of nineteen publications were found eligible for inclusion in the qualitative review, out of 101 search items. A total of 401 children with epileptic spasms were tried up to a maximum of 9.9-35 mg/kg/day dose with only mild adverse effects in a few patients. Total 20.8% (95% CI-11.4%-29.2%) and 23.4% (95% CI-17.8%-29.1%) patients had complete cessation of spasms and at least a 50% reduction in total spasm frequency as compared to baseline after starting zonisamide. Similarly, 20.3% (95% CI-10.1%-30.5%) had resolution of hypsarrhythmia in EEG after starting zonisamide. Conclusion: Zonisamide can reduce spasms in 21% of children with epileptic spasms, without major adverse effects. But there are only limited studies on epileptic spasms of sufficient quality to give high confidence in meta-analysis. Large controlled trials are needed in this regard to provide high-quality evidence favoring/disfavoring its use in patients with epileptic spasms.

Long-term effects of zonisamide in adult patients with intellectual disability.

This study aimed to evaluate the tolerability and efficacy of zonisamide (ZNS) in adult patients with drug-resistant epilepsy and intellectual disability (ID) at our epilepsy centre. By conducting a monocentric, open-label observational study based on standardized seizure records we retrospectively assessed 87 patients (39 female, mean age 40.6±13.6, range 18-75years) with ID and drug-resistant epilepsy. Evaluation, including calculation of retention rate, was performed for the intervals 3-6, 9-12 and 21-24months after ZNS initiation. The Clinical Global Impressions Scale-Improvement (CGI-I) was used to detect qualitative changes in seizure severity and clinical status. Via regression analysis and the generalized estimating equations approach, we examined changes in body weight and impact of patient age also considering associations with other patient characteristics. The retention rate after 24months was 60%. 28% discontinued ZNS therapy due to increasing seizure frequency, lack of efficacy or adverse events (AEs). Sedation (38%), language impairment (19%), challenging behaviour (10%), mild rash (10%) and dizziness (10%) were the commonest AEs. The responder rate was 40%, eight patients (9%) became seizure free. We found CGI-I to be dose-dependent. Regarding changes in body weight, we observed no difference between patients continuing or withdrawing ZNS therapy and responders or non-responders. Though, we identified older age as a significant risk factor for weight loss. Zonisamide may provide a safe and efficient therapeutic option for patients with ID and drug-resistant epilepsy. However, weight status should be carefully monitored, especially in elderly patients.

Randomised Controlled Trial Comparing Efficacy of Zonisamide 25 mg given in addition to standard treatment with standard treatment alone in Tremor dominant Parkinson’s Disease-A Pilot study. (5198)

Randomised Controlled Trial Comparing Efficacy of Zonisamide 25 mg given in addition to standard treatment with standard treatment alone in Tremor dominant Parkinson’s Disease-A Pilot study. (5198)

Zonisamide Therapy for Patients With Paroxysmal Kinesigenic Dyskinesia

BackgroundWe evaluated zonisamide therapy in patients with paroxysmal kinesigenic dyskinesia (PKD). MethodsWe analyzed zonisamide therapy in 17 patients with PKD at Saitama Children’s Medical Center between November 1994 and April 2020. We collected information regarding family history, previous history, age at onset, age at zonisamide commencement, dyskinesia characteristics, brain magnetic resonance imaging, interictal electroencephalography, treatment lag, zonisamide efficacy, zonisamide dose, serum zonisamide concentration, and adverse effects. We evaluated PKD frequency at six months after zonisamide therapy commencement. ResultsFourteen patients met the inclusion criteria. The median age at zonisamide therapy commencement was 12.8 (9.4 to 16.3) years. Zonisamide therapy was effective in 13 of 14 (92.9%) patients: complete remission for more than three months after zonisamide therapy (n = 7), decreased dyskinesia frequency by more than 90% (n = 4), dyskinesia frequency by 75% to 90% (n = 2), and no change of dyskinesia frequency (n = 1). The initial and maintenance zonisamide doses were 2.0 (1.4 to 3.8) and 2.0 (1.5 to 5.9) mg/kg/day, respectively. The median duration between zonisamide therapy commencement and dyskinesia decrease or cessation was 4 (1 to 60) days: 10 of 14 (71.4%) patients responded to zonisamide within one week after zonisamide therapy commencement. Regarding adverse effects, two patients experienced somnolence and one developed reduced perspiration. ConclusionsWe suggest that zonisamide monotherapy is effective for patients with PKD as a first-line treatment. We can evaluate the efficacy of zonisamide therapy within one week. Because zonisamide lacks the enzyme-inducing effects of carbamazepine and phenytoin, it may be useful for PKD treatment.

Zonisamide as an Adjunctive Treatment to Cognitive Processing Therapy for Veterans With Posttraumatic Stress Disorder and Comorbid Alcohol Use Disorder: A Pilot Study.

There are high rates of comorbid alcohol use disorder (AUD) among those who have posttraumatic stress disorder (PTSD). Ideally, treatment for comorbidity should address both disorders simultaneously. Zonisamide, an anticonvulsant, may be effective in decreasing alcohol use and may attenuate symptoms of PTSD. Treatment strategies can include medication in combination with a proven evidence-based psychotherapy designed to treat PTSD, such as cognitive processing therapy (CPT). This 12-week pilot study was designed to test feasibility, acceptability, and preliminary efficacy of zonisamide (400 mg) as an adjunct to CPT for veterans with PTSD and comorbid AUD. Veterans (n = 24) with PTSD and current alcohol dependence were randomized in a 3:1 ratio to receive zonisamide or placebo in a double-blind fashion. All subjects received CPT enhanced to include sessions addressing drinking behavior. Subjects overall reported a significant decrease in drinking outcomes, craving, and symptoms of PTSD. Zonisamide was well-tolerated and easily administered with CPT, which was also well-tolerated. Exploratory analysis of comparison of groups suggests there was no advantage of zonisamide vs placebo in drinking or PTSD outcomes. There was a numeric but nonsignificant higher rate of abstinence with zonisamide (50%) vs placebo (33%). The interpretation of the results is limited by the pilot nature of this study. The combination of psychosocial treatment with medication management mimics real-world treatment. In order to isolate the individual contributions of medication vs psychotherapy a much larger study would need to be conducted. (Am J Addict 2020;29:515-524).

Comparative analysis of zonisamide and topiramate use in treatment of pediatric epilepsy in real clinical practice: the results of a retrospective study and related clinical cases

Background. Comparative study of antiepileptic drugs allows to make the optimal choice in therapy.The aim of the study: a comparative analysis of the administration of two similar by chemical structure antiepileptic drugs (zonisamide and topiramate) in the outpatient practice in epilepsy in children, taking into account the efficacy and tolerability.Materials and methods. A retrospective analysis of outpatient charts of equal in number (n = 18) groups of patients with different forms of epilepsy treated with zonisamide and topiramate in monotherapy and in combined therapy was carried out.Results. In general, no statistically significant difference in the efficacy of zonisamide and topiramate was obtained (p = 0.692). Efficacy in structural focal epilepsy was also comparable (absence of seizures 54.6 % and 45.5 %, respectively). With comparable efficacy, zonisamide was administered to patients much later in the antiepileptic drugs (Me = 5) than topiramate (Me = 3). Side effects on zonisamide were registered in 27.8 %, side effects on topiramate – in 38.9 % (p = 0.480). The difference in the effect of these drugs on cognitive functions was noted.Conclusions. Zonisamide shows its effectiveness in different forms of epilepsy in children, despite the later appointment in practice. The drug is well tolerated and probably has less negative effect on children’s cognitive functions than topiramate.

Limited efficacy of zonisamide in the treatment of refractory infantile spasms.

A series of relatively small studies collectively suggest that zonisamide may be effective in the treatment of infantile spasms. Using a large single‐center cohort of children with infantile spasms, we set out to evaluate the efficacy and safety of zonisamide. We retrospectively identified all patients with infantile spasms who were treated with zonisamide at our center. For each patient, we recorded dates of birth, infantile spasms onset, response (if any), and most recent follow‐up. To quantify zonisamide exposure, we recorded daily dosage and patient weight at each sequential encounter so as to allow calculation of peak and weighted‐average weight‐based dosage. We identified 87 children who were treated with zonisamide, of whom 78 had previously been treated with hormonal therapy or vigabatrin. Peak and weighted‐average zonisamide dosage were 7.1 (interquartile range 3.6, 10.2) and 5.4 (interquartile range 3.0, 8.9) mg/kg/day, respectively. Whereas five (6%) patients exhibited resolution of epileptic spasms, only two (2%) patients exhibited video‐EEG confirmed resolution of both epileptic spasms and hypsarrhythmia (electroclinical response). Importantly, both electroclinical responders had not previously been treated with hormonal therapy or vigabatrin; in contrast, none of the 78 children with prior failure of hormonal therapy or vigabatrin subsequently responded to zonisamide. Zonisamide was well tolerated, and there were no deaths. This study suggests that zonisamide exhibits favorable tolerability but very limited efficacy among patients who do not respond to first‐line therapy.

Effect of zonisamide on parkinsonism in patients with dementia with Lewy bodies: A phase 3 randomized clinical trial

IntroductionZonisamide is approved in Japan for treating motor dysfunction in Parkinson's disease, and might also be effective for parkinsonism in patients with dementia with Lewy bodies (DLB). Our study evaluated the safety and efficacy of zonisamide for treating parkinsonism in patients with DLB. MethodsThis multicenter, randomized, double-blind, phase 3 trial was conducted in Japan between April 2015 and November 2017. Following a 4-week run-in period, outpatients diagnosed with probable DLB who had developed parkinsonism were randomized to receive oral zonisamide (25 or 50 mg/day) or placebo for 12 weeks, followed by a 40-week open-label extension. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part III total score at Week 12. ResultsOf 351 patients randomized, 346 (mean age, 77.2 years; 188 males) were included in the modified intention-to-treat population. At Week 12, the group difference (least squares mean ± SEM) for changes from baseline (vs placebo) in UPDRS part III total score was −2.7 ± 0.9 (95% confidence interval [CI]: −4.4, −0.9, P = 0.005) in the zonisamide 25-mg group and −2.6 ± 0.9 (95% CI: −4.4, −0.8, P = 0.005) in the zonisamide 50-mg group. Adverse events were reported in 47.1%, 48.7%, and 54.5% of patients in the placebo and zonisamide 25- and 50-mg groups, and led to treatment discontinuation in 5.0%, 4.3%, and 9.8% of patients, respectively. ConclusionDaily administration of 25- or 50-mg zonisamide significantly improved motor function compared with placebo; both doses were safe and well tolerated in patients with DLB.

Long-term Efficacy of Zonisamide on Parkinsonism in Dementia with Lewy Bodies: A Post-hoc Analysis of Phase 3 Trial (P4.1-012)

Long-term Efficacy of Zonisamide on Parkinsonism in Dementia with Lewy Bodies: A Post-hoc Analysis of Phase 3 Trial (P4.1-012)

Current Status of Antiepileptic Drugs as Preventive Migraine Therapy.

Antiepileptic drugs (AEDs) are an important class of agents used in the treatment of migraine, a neurological disorder that imparts significant socioeconomic burden. It is important for neurologists to understand the rationale for AEDs in migraine-preventive treatment, as well as each agent's efficacy and tolerability profile, in order to best determine clinical care. This article specifically provides the following: (1) a review of the mechanism of action, efficacy, and tolerability of topiramate and divalproex sodium/sodium valproate, the most widely used AEDs for migraine prevention, (2) a discussion on emerging evidence regarding the efficacy of zonisamide and levetiracetam, and (3) comments on gabapentin, pregabalin, carbamazepine, oxcarbazepine, and lamotrigine, AEDs which have insufficient evidence for use in migraine prevention. The potential role for new extended-release formulations of topiramate in migraine prevention is discussed. There is substantial evidence supporting the use of AEDs in migraine prevention. Specific agents should be chosen based on their efficacy and tolerability profiles. Further studies are needed to determine the efficacy of the newer AEDs, zonisamide and levetiracetam, in migraine prevention and to clarify the role of gabapentinoids in headache management.

Safety And Efficacy of Zonisamide in Refractory Epilepsy Patients: Clinical Experience from A Tertiary Center

Safety And Efficacy of Zonisamide in Refractory Epilepsy Patients: Clinical Experience from A Tertiary Center

Efficacy of zonisamide on interictal electroencephalography in familial spontaneous epileptic cats.

Objectives The effectiveness of zonisamide (ZNS) against spontaneous epilepsy in cats has not yet been described. The purpose of this study was to investigate the effect of ZNS on interictal paroxysmal discharges (PDs) using scalp electroencephalography (EEG) in familial spontaneous epileptic cats (FSECs). Methods Eight FSECs were evaluated (six males and two females). Scalp EEG measurements were performed once a week for 3 weeks before ZNS administration (Pre-ZNS). Thereafter, administration of ZNS was started and an adjustment period was instituted until the drug in plasma achieved the steady state. When ZNS in plasma was confirmed to be within 10-40 μg/ml, scalp EEG measurements were performed once a week for 3 weeks (Post-ZNS). The number of PDs (counts/min) were compared between Pre-ZNS and Post-ZNS treatment. Results The median number of PDs for Pre-ZNS and Post-ZNS were 0.43/min (0.13-0.82/min) and 0.28/min (0.07-0.87/min), respectively. The number of PDs Post-ZNS was significantly reduced compared with Pre-ZNS ( P = 0.02). Conclusions and relevance This study showed that ZNS, within the recommended therapeutic range suggested for use in humans and dogs (10-40 µg/ml), reduced the number of PDs recorded on EEG in FSECs that are considered a model for cats with idiopathic epilepsy. Although phenobarbital is the antiepileptic drug of choice for epileptic cats, the results of this research provide evidence to support the use of ZNS in cats with phenobarbital-resistant epilepsy or for cats that cannot use phenobarbital due to adverse side effects.

ZonisamideによるLewy小体型認知症の行動・心理症状への効果の検証 ―有効性探索試験―

ZonisamideによるLewy小体型認知症の行動・心理症状への効果の検証 ―有効性探索試験―

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

A prospective, multicentric, noncomparative open-label observational study was conducted to evaluate the safety and efficacy zonisamide in Indian adult patients for the treatment of partial, generalized, or combined seizures. A total of 655 adult patients with partial, generalized, or combined seizures from 30 centers across India were recruited after initial screening. Patients received 100 mg zonisamide as initiating dose as monotherapy/adjunctive therapy for 24 weeks, with titration of 100 mg every 2 weeks if required. Adverse events, responder rates, and seizure freedom were observed every 4 weeks. Efficacy and safety were also assessed using Clinicians Global Assessment of Response to Therapy and Patients Global Assessment of Tolerability to Therapy, respectively. Follow-up was conducted for a period of 24 weeks after treatment initiation. A total of 655 patients were enrolled and received the treatment and 563 completed the evaluation phase. A total of 20.92% of patients received zonisamide as monotherapy or alternative monotherapy and 59.85% patients received zonisamide as first adjunctive therapy. Compared with baseline, 41.22% of patients achieved seizure freedom and 78.6% as responder rate at the end of 24 week study. Most commonly reported adverse events were loss of appetite, weight loss, sedation, and dizziness, but discontinuation due to adverse events of drug was seen in 0.92% of patients. This open label real-world study suggests that zonisamide is an effective and well-tolerated antiepileptic drug in Indian adults for treatment of partial, generalized as well as combined seizures type. No new safety signals were observed.

Safety and Efficacy of Zonisamide in Patients with Epilepsy: A Post-Marketing Surveillance Study.

Background and Purpose:Zonisamide (ZNS) is one of new antiepileptic drug, which is known to inhibit seizure through multiple mechanisms of action. In Korea, ZNS was approved as an antiepileptic drug in 1992 and has been used for epilepsy patients with partial and generalized seizures. The objective of this study was to investigate the efficacy and tolerability of ZNS in patients with epilepsy and to identify the incidence of adverse events in real clinical setting.Methods:This study was carried out in patients who received ZNS for epilepsy. Patients who were observed for at least 12 weeks after treatment with ZNS were included as evaluable subjects. Information regarding the status and type of adverse events occurring during the course of treatment with ZNS was obtained regardless of causal relationship to ZNS and efficacy was assessed by the study physicians and patients at 12 weeks post dose of ZNS.Results:A total of 1,948 patients were included in the study, and ZNS efficacy was evaluated in 1,744 patients. ZNS was used as a monotherapy in 1,095 patients and as an adjunctive drug in 853 patients. Of the total patients, 1,345 (69.1%) patients had partial seizure, 563 patients had generalized seizure, and 40 patients were undetermined. Adverse events were reported in 65 patients (3.34%) including 1 case of Stevens-Johnson syndrome, but no incidence of serious unexpected adverse drug reactions were reported. 755 patients (43.29%) became seizure free with ZNS treatment, and additional 322 patients (18.41%) experienced marked improvement with ZNS treatment.Conclusions:Our study shows the safety and tolerability of ZNS treatment in patients with epilepsy in real clinical setting. In addition, ZNS was found to be an effective option as a monotherapy or in patients with generalized seizure.

Randomized placebo‐controlled trial of zonisamide in patients with Parkinson's disease

AbstractBackgroundWe previously showed that zonisamide significantly improved parkinsonian symptoms by a multicenter, double‐blind clinical trial.AimTo confirm the efficacy of zonisamide on Parkinson's disease, a phase 3, randomized, placebo‐controlled, multicenter, double‐blind trial was carried out in Japan.MethodsParticipants had advanced Parkinson's disease taking L‐dopa with at least one other antiparkinson drug, but were developing a deterioration of response to L‐dopa therapy. The trial consisted of a 2‐week initial phase (single‐blind, with administration of placebo) and a 12‐week treatment phase (double‐blind, with patients randomly assigned to either placebo, or zonisamide 25 or 50 mg/day). Patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS).ResultsA total of 185 patients (mean age 64.8 years; mean duration 7.5 years) were included in the efficacy analysis (placebo, zonisamide 25 mg, 50 mg; 63, 61, 61 patients, respectively). When compared with the placebo group, the UPDRS Part III total score at final assessment (the primary end‐point for efficacy) significantly improved (P = 0.029) in the zonisamide 25 mg group. After 12 weeks of therapy, the UPDRS Part III total score significantly improved in both the zonisamide 25 mg (P = 0.038) and 50 mg groups (P = 0.049), compared with the placebo group. Neither the zonisamide 25 mg nor 50 mg group differed significantly from the placebo group in the incidence of adverse events (P = 0.363 and P = 0.713, respectively).ConclusionThese findings confirmed that zonisamide is well tolerated and efficacious in the treatment of advanced Parkinson's disease.