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PubMed2003

The effect of systemic zonisamide (Zonegran) on thermal hyperalgesia and mechanical allodynia in rats with an experimental mononeuropathy.

UNLABELLED: We studied the ability of zonisamide (Zonegran) to relieve thermal hyperalgesia and/or mechanical allodynia in the chronic constriction injury model of neuropathic pain. Zonisamide (25, 50, or 100 mg/kg) or saline was administered in a blinded, randomized manner by intraperitoneal injection on postoperative days (PODs) 4, 5, and 6. Paw withdrawal latency (PWL) to heat, paw withdrawal response to von Frey monofilaments, and pain scores based on weight-bearing were tested: before surgery; before and after zonisamide or saline (PODs 4, 5, and 6); and on POD 9. Systemic zonisamide relieved thermal hyperalgesia in a dose-dependent manner. All PWLs were significantly increased after zonisamide administration compared with pre-zonisamide measurements, except with the 100 mg/kg dose on POD 5. After zonisamide 100 mg/kg administration, there was a sustained increase in PWL on PODs 5 and 9, with significant carryover effect from the previous dose. However, zonisamide had little effect on mechanical allodynia, except at the 100 mg/kg dose, which was sedating in the rat. At the 100 mg/kg dose, paw withdrawal response was increased on PODs 4 and 5, whereas pain scores were reduced on PODs 4, 5, and 6. Pain scores were inconsistently reduced after 50 mg/kg or 25 mg/kg doses. IMPLICATIONS: Zonisamide causes a dose-related decrease in heat sensitivity in a rat model of neuropathic pain, but relieves mechanical sensitivity only in a dose that is sedating to the rat. Zonisamide may be useful in the treatment of some types of neuropathic pain.

Animals↗
PubMed1987

General pharmacology of the novel antiepileptic compound zonisamide. 1st communication: effects on central nervous system.

The effects of 1,2-benzisoxazole-3-methanesulfonamide (zonisamide, AD-810, CI-912), an antiepileptic compound, on the central nervous system were compared with those of carbamazepine and acetazolamide in experimental animals. 1. Zonisamide at an oral dose of 100 mg/kg was without effect on general behavior in mice except lowerings of pelvic, tail and body positions and ptosis. In rats, zonisamide slightly decreased the body temperature at the same dose. 2. Zonisamide (50 mg/kg p.o.) did not affect spontaneous alteration behavior and active avoidance performance in mice, although it impaired the acquisition of step-down passive avoidance behavior in mice. Carbamazepine (50 mg/kg) deteriorated the spontaneous alternation behavior. 3. Zonisamide (40 mg/kg i.v.) did not affect the relative power of cortical EEGs in gallamine-immobilized cats. Caudate spindles and recruiting responses, induced by electrical stimulation of the head of the caudate nucleus and the ventralis anterior thalamus, respectively, were not affected with the same dose of zonisamide in cats. On the other hand, carbamazepine (5 mg/kg) decreased the beta 2 relative power in the cortex, and enhanced both caudate spindles and recruiting responses. 4. Zonisamide (10 mg/kg i.v.) and carbamazepine (3 mg/kg) showed a tendency to depress the flexor reflex without affecting the neuromuscular transmission in anesthetized cats. 5. The central effects of zonisamide clearly differed from those of acetazolamide. Namely, acetazolamide markedly decreased brain pH at 25 mg/kg i.v., and increased regional cerebral blood flow at 100 mg/kg p.o. in rats. Zonisamide at 50 mg/kg i.v. and 100 mg/kg p.o. did not affect brain pH and regional cerebral blood flow, respectively. In addition, zonisamide (100 mg/kg p.o.) decreased brain contents of dopamine metabolite, DOPAC, with slight increase of a serotonin metabolite, 5-HIAA, in mice, and decreased brain contents of dopamine metabolites, DOPAC and HVA, in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

General pharmacology of the novel antiepileptic compound zonisamide. 2nd communication: effects on cardiovascular, visceral, renal and blood functions.

The effects of 1,2-benzisoxazole-3-methanesulfonamide (zonisamide, AD-810, CI-912), an antiepileptic compound, on the cardiovascular, visceral, renal and blood functions were compared with those of carbamazepine and, in part, acetazolamide in experimental animals. 1. Zonisamide (30 mg/kg i.v.) transiently lowered the blood pressure and decreased the blood flows in the carotid and femoral arteries in anesthetized dogs. The effects were 3 times less potent than those of carbamazepine, Zonisamide, when orally administered, did not affect the blood pressure even at 300 mg/kg in conscious rats. 2. Zonisamide little affected the autonomic nervous system even at high doses. In anesthetized cats, contractions of the nictating membrane by electrical stimulation of the cervical sympathetic nerve, pressor responses to norepinephrine, and depressor responses to acetylcholine, all were not modified with zonisamide (100 mg/kg i.v.). In isolated guinea-pig ileum, contractions induced by acetylcholine, histamine and bradykinin were not affected by zonisamide up to a concentration of 10(-3) g/ml zonisamide, although those by serotonin and nicotine were depressed with high concentrations over 10(-5) g/ml. 3. With 100 mg/kg p.o., zonisamide decreased the gastric juice volume and pH in pylorus ligated rats, and depressed gastric emptying in rats, but did not inhibit the intestinal transit of charcoal meal in mice. These effects were less potent than those of carbamazepine. 4. Zonisamide increased the urine volume, pH, and Na+ and K+ concentrations in rats and anesthetized dogs. The renal blood flow and glomerular filtration rate were little changed with the high doses of zonisamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Zonisamide add-on for drug-resistant partial epilepsy.

BACKGROUND: The majority of people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding zonisamide, when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the effects of zonisamide when used as an add-on treatment for people with drug-resistant partial epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group Specialized Register (August 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005). In addition, we contacted Eisai Limited (makers and licensees of zonisamide) and experts in the field to seek any ongoing/unpublished studies. SELECTION CRITERIA: Randomized placebo controlled add-on trials of zonisamide in people with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Outcomes were: (1) 50% or greater reduction in total seizure frequency; (2) treatment withdrawal; (3) adverse events. Primary analyses were intention-to-treat. Summary relative risks (RRs) were estimated for each outcome. MAIN RESULTS: Four trials (850 participants) were included. The overall RR with 95% confidence intervals (CIs) for 50% reduction in seizure frequency compared to placebo for 300 to 500 mg/day of zonisamide was 2.44 (95% CI 1.81 to 3.30). The RR for any dose zonisamide (100 to 500 mg per day) was 2.35 (1.74 to 3.17). Two trials provide evidence of a dose response relationship for this outcome. The RR for treatment withdrawal for 300 to 500 mg/day zonisamide compared to placebo was 1.64 (1.20 to 2.26), and for 100 to 500 mg per day was 1.47 (1.07 to 2.02). The CIs of the following adverse effects indicate that they are significantly associated with zonisamide: ataxia 4.50 (99% CI 1.05 to 19.22); dizziness 1.77 (99% CI 1.00 to 3.12); somnolence 1.96 (99% CI 1.12 to 3.44); agitation 2.37 (99% CI 1.00 to 5.64); and anorexia 3.00 (99% CI 1.31 to 6.88). AUTHORS' CONCLUSIONS: Zonisamide has efficacy as an add-on treatment in people with drug-resistant partial epilepsy. Minimum effective and maximum tolerated doses cannot be identified. The trials reviewed were of 12 week duration and results cannot be used to confirm longer periods of effectiveness in seizure control. The results cannot be extrapolated to monotherapy or to people with other seizure types or epilepsy syndromes.

Anticonvulsants↗
PubMed2004

Zonisamide: chemistry, mechanism of action, and pharmacokinetics.

Zonisamide is a synthetic 1,2-benzisoxazole-3-methanesulfonamide with anticonvulsant properties. The sulfamoyl group on zonisamide was expected to suppress seizures in a manner similar to another sulfonamide analogue, acetazolamide, through inhibition of carbonic anhydrase. However, this does not appear to be the primary mechanism of action since zonisamide requires much higher doses than acetazolamide to achieve equivalent titration in vivo. Studies with cultured neurons indicate that zonisamide blocks repetitive firing of voltage-sensitive sodium channels and reduces voltage-sensitive T-type calcium currents without affecting L-type calcium currents. Its dual mechanism of action may explain its efficacy in patients resistant to other antiepileptic drugs (AEDs). Zonisamide has a pharmacokinetic profile favorable for clinical use. It is rapidly and completely absorbed and has a long half-life (63-69h in healthy volunteers) which allows twice-daily, or even once-daily, dosing. Zonisamide is not highly bound to plasma proteins. Consequently, it does not affect protein binding of other highly protein-bound AEDs. Furthermore, zonisamide does not induce its own metabolism and does not induce liver enzymes. However, since zonisamide is metabolized by cytochrome P450, liver enzyme-inducing AEDs will increase zonisamide clearance, and dosage adjustments may be necessary when it is used in combination with certain AEDs.

Animals↗
PubMed1996

[Research and development of zonisamide, a new type of antiepileptic drug].

Zonisamide (1,2-benzisoxazole-3-methanesulfonamide, AD-810) is a broad spectrum antiepileptic drug which has been launched in Japan and South Korea. It lacks the ureide structure included in most of the existing antiepileptic drugs. Zonisamide was synthesized by the sulfonation and the successive amination of 1,2-benzisoxazole-3-acetic acid in a very poor yield. After several efforts to optimize the compound, zonisamide was selected based on the balance of the efficacy and safety. The yield was greatly improved by the development of new synthetic routes. Zonisamide suppressed maximal electroshock seizures in mice, rats, rabbits and dogs. Its therapeutic plasma concentration range between anticonvulsant and neurotoxic effects was much wider than that of the existing antiepileptic drugs. In electroencephalographic studies on animal models of epilepsy, zonisamide, like phenytoin and carbamazepine, restricted the spread or propagation of seizures and, like sodium valproate, it suppressed the epileptogenic focus activity. Zonisamide was effective in several kindling models. In clinical studies, zonisamide exerted the efficacy against partial seizures (simple, complex, secondarily generalized seizures) and some generalized seizures (tonic-clonic, tonic, atypical absence seizures) that were comparable to that of carbamazepine and sodium valproate, respectively. Zonisamide was also effective in monotherapy. The adverse effects related with zonisamide were mainly drowsiness, ataxia, loss of appetite and gastrointestinal symptoms. Serious adverse effects which may be life-threatening have not been reported.

Animals↗
PubMed2001

Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures.

BACKGROUND: Zonisamide is a sulfonamide antiepilepsy drug with sodium and calcium channel-blocking actions. Experience in Japan and a previous European double-blind study have demonstrated its efficacy against partial-onset seizures. METHODS: A randomized, double-blind, placebo-controlled trial enrolling 203 patients was conducted at 20 United States sites to assess zonisamide efficacy and dose response as adjunctive therapy for refractory partial-onset seizures. Zonisamide dosages were elevated by 100 mg/d each week. The study design allowed parallel comparisons with placebo for three dosages and a final crossover to 400 mg/d of zonisamide for all patients. The primary efficacy comparison was change in seizure frequency from a 4-week placebo baseline to weeks 8 through 12 on blinded therapy. RESULTS: At 400 mg/d, zonisamide reduced the median frequency of all seizures by 40.5% from baseline, compared with a 9% reduction (p = 0.0009) with placebo treatment, and produced a > or =50% seizure reduction (responder rate) in 42% of patients. A dosage of 100 mg/d produced a 20.5% reduction in median seizure frequency (p = 0.038 compared with placebo) and a dosage of 200 mg/d produced a 24.7% reduction in median seizure frequency (p = 0.004 compared with placebo). Dropouts from adverse events (10%) did not differ from placebo (8.2%, NS). The only adverse event differing significantly from placebo was weight loss, though somnolence, anorexia, and ataxia were slightly more common with zonisamide treatment. Serum zonisamide concentrations rose with increasing dose. CONCLUSION: Zonisamide is effective and well tolerated as an adjunctive agent for refractory partial-onset seizures. The minimal effective dosage was 100 mg/d, but 400 mg/d was the most effective dosage.

Adolescent↗
PubMed2005

Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse.

Some antiepileptic drugs are used clinically to relieve neuropathic pain. We have evaluated the effects and investigated the possible mechanisms of action of zonisamide, an antiepileptic drug, on thermal hyperalgesia and tactile allodynia in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. Subcutaneously administered zonisamide (10 and 30 mg/kg) produced antihyperalgesic and antiallodynic effects in a dose-dependent manner; these effects were manifested by elevation of the withdrawal threshold in response to a thermal (plantar test) or mechanical (von Frey) stimulus, respectively. Similar analgesic effects were obtained in both the plantar and von Frey tests when zonisamide was injected either intracerebroventricularly (i.c.v., 10 and 30 microg) or intrathecally (i.t., 10 and 30 microg). It is thought that this elevation of the thermal and mechanical withdrawal thresholds after local injection of zonisamide is not generated secondarily via impaired motor activity, since zonisamide (30 microg, i.c.v. or i.t.) did not affect locomotor activity, as assessed in sciatic-nerve-ligated mice. Moreover, the nitric oxide synthase inhibitor L-NAME, when injected either i.c.v. or i.t., potentiated the analgesic effects of zonisamide. In contrast, neither i.c.v. nor i.t. zonisamide produced antinociceptive effects against acute thermal and mechanical nociception in non-ligated mice. Together, following peripheral nerve injury, it appears that zonisamide produces centrally mediated antihyperalgesic and antiallodynic effects partly via the blockade of nitric oxide synthesis.

Animals↗
PubMed2004

Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol-norethindrone oral contraceptive in healthy women.

BACKGROUND: Several antiepileptic drugs have clinically significant pharmacokinetic interactions with oral contraceptives (OCs) that may result in contraceptive failure. OBJECTIVE: The aim of this study was to assess the effect of zonisamide on the pharmacokinetics of the individual components of a combination OC (ethinyl estradiol [EE] 0.035 mg and norethindrone [NOR] 1 mg) and on pharmacodynamic variables that may be increased in the event of reduced contraceptive efficacy (concentrations of serum luteinizing hormone [LH], follicle-stimulating hormone [FSH], and progesterone). METHODS: This was a single-center, open-label, 1-sequence, crossover study. Healthy, premenopausal women received the combination OC for three 28-day cycles (combination OC for 21 days, followed by placebo for 7 days). Following stabilization on the OC during the first cycle, blood was collected during cycle 2 for the determination of serum EE and NOR profiles (day 14) and serum LH, FSH, and progesterone concentrations (days 13-15). Starting on day 15 of cycle 2, zonisamide was administered orally at 100 mg/d and titrated to a target dose of 400 mg/d. EE and NOR profiles and serum LH, FSH, and progesterone concentrations were obtained again in cycle 3 (in the presence of zonisamide) and compared with those from cycle 2 (in the absence of zonisamide). RESULTS: Thirty-seven healthy premenopausal women (mean age, 26.1 years [range, 18-51 years]; mean body weight, 65.5 kg [range, 50.4-93.1 kg]; mean height, 165.8 cm [range, 152.4-182.9 cm]) received > or =1 dose of zonisamide. Of the 33 subjects (89.2%) who completed the study, 26 (78.8%) underwent titration to a stable zonisamide dose of 400 mg/d. For EE, the mean (SD) AUC over a 24-hour dosing interval (AUC(tau)) was 1139 (317) pg.h/mL in cycle 2 and 1143 (312) pg.h/mL in cycle 3; the mean C(max) in the respective cycles was 133 (39) and 141 (46) pg/mL. For NOR, the corresponding values were 140 (48) and 159 (46) ng.h/mL for AUC(tau) and 21 (5.4) and 23 (6.7) ng/mL for C(max). The 90% Cls for the geometric mean ratios (cycle 3:cycle 2) for AUC(tau) and C(max) fell within the accepted range for lack of interaction (0.80-1.25). There were no increases in LH, FSH, or progesterone concentrations between cycle 2 and cycle 3. CONCLUSIONS: In these healthy volunteers, steady-state zonisamide dosing had no clinically significant effect on the pharmacokinetics of EE or NOR. There was no pharmacodynamic evidence that zonisamide is likely to reduce the contraceptive effectiveness of OCs containing EE and NOR.

Adult↗
PubMed2006

Zonisamide in the management of epilepsy--Japanese experience.

Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved in Europe for the adjunctive treatment of refractory partial seizures in adults, has undergone extensive evaluation in pre- and post-marketing double-blind and open-label studies in Japan (where zonisamide is used widely to treat partial and generalised seizures in adults and children). These data indicate that the clinical benefit of zonisamide extends across a range of seizure types and patient ages. In an analysis based on a mixture of controlled and open studies in adults and children with partial seizures, 51-57% responded to zonisamide treatment (achieving >or=50% reduction in baseline seizure frequency). Efficacy extends across a range of generalised seizures and 22-66% of adults and children experiencing tonic-clonic, tonic, clonic, myoclonic or absence seizures responded to treatment. Even greater responder rates have been reported when zonisamide was used as monotherapy for partial seizures and generalised seizures in patients refractory to other AEDs or with newly diagnosed epilepsy. Zonisamide is also efficacious in paediatric epilepsy syndromes, including Lennox-Gastaut Syndrome, West Syndrome and Ohtahara Syndrome. Across the spectrum of epilepsy syndromes studied, zonisamide is well-tolerated with a low incidence of adverse events, which are generally mild and CNS-related. These data indicate that zonisamide represents a valuable broad-spectrum option for the treatment of epilepsy.

Adolescent↗
PubMed2001

Effect of immobilization stress on anticonvulsant actions and pharmacokinetics of zonisamide in mice.

The effects of immobilization stress on anticonvulsant actions and pharmacokinetics of zonisamide were investigated in mice. Oral administrations of zonisamide (10, 20, and 50 mg/kg) dose-dependently reduced incidence of tonic extension (TE) induced by maximal electroshock seizure (MES). Immobilization stress for 2 h immediately after the administration of zonisamide further enhanced the anticonvulsive actions of it. On the other hand, the serum zonisamide concentrations in stressed group were lower during the first 30 min after the administration compared with that in nonstressed control group. Thereafter, there were no significant differences in the serum concentrations between two groups. The brain zonisamide concentration and the concentration ratio of brain/serum at 2 h after administration of zonisamide (50 mg/kg) were significantly higher in stressed group, rather than that in the nonstressed control group without changing the serum concentration. These results suggest that immobilization stress enhances anticonvulsant actions of zonisamide, and that increases of brain zonisamide concentration by immobilization stress may be related with this phenomenon.

Animals↗
PubMed2004

Zonisamide monotherapy in a multi-group clinic.

OBJECTIVE: Reports on zonisamide monotherapy are limited despite favourable preliminary data, and typically restricted to tertiary referral centres. The goal of this study is to report clinical experience with zonisamide monotherapy in a large, multi-group clinic setting. METHODS: We reviewed the charts of patients treated with zonisamide monotherapy in the Neurology Department of the Kelsey-Seybold Clinic (Houston, Texas) during an 18-month period. We analysed subgroups of patients who were naive to antiepileptic drug (AED) therapy (Group 1) and those who had previous exposure to AEDs (Group 2). RESULTS: The study included 54 paediatric and adult patients with a variety of seizure types: 15 patients in Group 1 and 39 patients in Group 2. Mean maintenance zonisamide dosages in the two groups were similar (193 mg/day in Group 1 vs. 218 mg/day in Group 2). Thirty-eight patients (70.4%) continued zonisamide monotherapy, with 7 patients (13.0%) adding a second AED and 9 patients (16.7%) switching to a different drug. Of the 24 patients who became seizure free on zonisamide monotherapy, 11 were on the 100-mg initial dosage. Zonisamide monotherapy was well tolerated. CONCLUSIONS: Zonisamide monotherapy is safe and effective for a variety of seizure types and may be appropriate as first-line therapy in some cases.

Adolescent↗
PubMedDate not supplied

Zonisamide in the treatment of painful diabetic neuropathy: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Painful diabetic neuropathy is a form of neuropathic pain frequently encountered as a complication of diabetes mellitus types I and II. Pharmacotherapy is one modality of treatment for this distressing and often disabling condition, but there is no medication available that consistently provides adequate pain relief with acceptable safety and tolerability. Tricyclic antidepressants, certain antiepileptic drugs, and opioids have been shown in randomized, controlled trials to be of benefit in painful diabetic neuropathy, although none has Food and Drug Administration (FDA)-approved labeling for this indication. STUDY OBJECTIVE: To analyze the safety and efficacy of zonisamide in the treatment of painful diabetic neuropathy. This pilot study is the first randomized, controlled trial of zonisamide for the treatment of any neuropathic pain disorder. STUDY DESIGN: Forty-two patients 18-80 years of age with type I or type II diabetes mellitus and at least a 3-month history of painful diabetic neuropathy were screened in the study, and 25 were randomized to zonisamide (N = 13) or placebo (N = 12). The study drug was titrated over a 6-week period and continued at a fixed dosage for a 6-week maintenance period. The mean dosage of zonisamide for the maintenance phase was 540 mg/day. OUTCOME MEASURES: Patients kept a daily log of their pain using both a 0-100 mm visual analog scale and a 0-10 Likert scale. RESULT: Pain scores on both the visual analog scale and the Likert scale decreased more for the zonisamide group compared with the placebo group, regardless of whether the comparison was made for the intent-to-treat population, the population that entered the maintenance phase, or the completer population, but these differences did not reach statistical significance. Tolerability of zonisamide was only fair in this study, which had a high number of dropouts from the zonisamide group. CONCLUSION: A larger randomized, controlled trial is needed to establish the efficacy and tolerability of zonisamide for painful diabetic neuropathy.

Antioxidants↗
PubMed1997

The role of mammalian intestinal bacteria in the reductive metabolism of zonisamide.

Zonisamide (1,2-benzisoxazole-3-methanesulphonamide), a new anticonvulsant, is mainly metabolized to 2-sulphamoylacetylphenol by reduction of the benzisoxazole ring. Recent studies have shown that mammalian liver enzymes are responsible for the reduction of zonisamide. Because intestinal bacteria can also mediate the reduction of xenobiotics, this study was designed to evaluate the role of intestinal bacteria in in-vivo reductive metabolism of zonisamide. Treatment of rats with antibiotics significantly reduced the urinary and faecal excretion of 2-sulphamoylacetylphenol after oral administration of zonisamide. Re-contamination of the antibiotic-treated rats with microflora restored the excretion of the metabolite. The caecal contents of the control rats had significant zonisamide reductase activity, whereas little or no zonisamide reductase activity was observed with the caecal contents of the antibiotic-treated rats. Eight pure strains of intestinal bacteria were tested for zonisamide reductase activity and the highest was observed in Clostridium sporogenes. We concluded that intestinal bacteria play a major role in the reductive metabolism of zonisamide to 2-sulphamoylacetylphenol in-vivo.

Aldehyde Oxidase↗
PubMed2006

Zonisamide in the treatment of binge eating disorder with obesity: a randomized controlled trial.

OBJECTIVE: Binge eating disorder (BED) is associated with obesity. Zonisamide is a novel antiepileptic drug associated with weight loss. The purpose of this study was to evaluate zonisa-mide in the treatment of BED associated with obesity. METHOD: In this 16-week, single-center, randomized, double-blind, placebo-controlled, flexible-dose (100-600 mg/day) trial, 60 outpatients with DSM-IV-TR BED received zonisamide (N = 30) or placebo (N = 30). The primary outcome measure was weekly frequency of binge eating episodes. The primary analysis of efficacy was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the effect measure. Patients were enrolled from September 5, 2003, through October 1, 2004. RESULTS: Compared with placebo, zonisamide was associated with a significantly greater rate of reduction in binge eating episode frequency (p = .021), body weight (p < .001), BMI (p = .001), and scores on the Clinical Global Impressions-Severity scale (p < .001), Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (p < .001), and Three Factor Eating Questionnaire disinhibition scales (p < .001). Plasma ghrelin concentrations increased with zonisamide but decreased with placebo (p = .001). The mean (SD) zonisamide daily dose at endpoint evaluation was 436 (159) mg/day. Twelve patients (N = 8 receiving zonisamide, N = 4 receiving placebo) discontinued because of adverse events. The most common reasons for discontinuing zonisamide were accidental injury with bone fracture (N = 2), psychological complaints (N = 2), and cognitive complaints (N = 2). CONCLUSION: Zonisamide was efficacious, but not well tolerated, in the short-term treatment of BED associated with obesity. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00221442.

Adult↗
PubMed1994

Zonisamide reduces hypoxic-ischemic brain damage in neonatal rats irrespective of its anticonvulsive effect.

The neuroprotective effect of a novel anticonvulsant, zonisamide, was investigated in neonatal rats with hypoxic-ischemic brain damage. Rats underwent left carotid ligation followed by hypoxic exposure (8% O2) for 2.5 h. When zonisamide (75 mg/kg) was administered i.p. 1 h before hypoxia, it reduced the cortical infarction volume to 6 +/- 5% (mean +/- S.E.M.) from 68 +/- 7% in vehicle-treated controls and the striatal volume to 8 +/- 4% from 78 +/- 7%. Zonisamide also reduced neuronal necrosis in 5 hippocampal regions (the dentate gyrus, CA4, CA3, CA1, and the subiculum). The plasma zonisamide concentration before and after hypoxia was 47.9 +/- 2.0 microgram/ml and 42.3 +/- 3.9 microgram/ml, respectively. Epidural electrodes were implanted in 6 pups one day before hypoxia-ischemia. Electroencephalograms were recorded during hypoxia-ischemia in rats given zonisamide or vehicle before the insult. The intensity of seizure activities was similar in the zonisamide-treated pups and the vehicle-treated controls. These findings demonstrate that zonisamide reduces neonatal hypoxic-ischemic brain damage and that this protective effect does not depend on its anticonvulsant action.

Animals↗
PubMed1993

Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial.

The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped from 12/month to 7.1/month with no changes in the placebo group (P < 0.007). During the 12-week double-blind phase a 50% reduction of all seizures was recorded in 29.9% of the patients treated with zonisamide vs. 9.4% during placebo. Complete remission was observed during treatment with zonisamide in 6.2%. The plasma concentrations of the concomitant antiepileptic drugs did not change markedly when zonisamide was added. Adverse events, mostly fatigue, somnolence, dizziness and ataxia, occurred in 59.2% of the patients compared to 27.9% during placebo. Zonisamide was withdrawn in two patients due to adverse events. Kidney stones were not observed nor any relevant clinical chemistry or hematological changes. Zonisamide is an effective antiepileptic drug for add-on treatment of refractory partial epilepsy.

Adolescent↗
PubMed2004

Zonisamide and associated oligohidrosis and hyperthermia.

Zonisamide is an antiepileptic agent that is indicated as adjunctive therapy for the treatment of partial seizures in adults. Oligohidrosis has been reported in a small number of patients receiving zonisamide and, in a proportion of these patients, hyperthermia has occurred. Most reports of hyperthermia have been in children, typically occurring during the summer months. However, the mechanism of zonisamide-associated oligohidrosis is not fully understood. Thirteen events of oligohidrosis, or hyperthermia, associated with zonisamide were reported in the US during the 3 years after zonisamide was approved, an estimated incidence of 1 case per 4590 patient-years. These events happened mostly in children. In Japan, all reported cases of zonisamide-associated oligohidrosis or hyperthermia have been in children, with an incidence of 1 case per 10,000 pediatric-years during the first 11 years of marketing. In each case, oligohidrosis was reversible upon discontinuation of zonisamide. Ensuring that children remain cool and well hydrated during hot weather can minimize the potential for hyperthermia resulting from oligohidrosis.

Adult↗