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PubMed2003

Visual hallucinations associated with zonisamide.

Zonisamide is a broad-spectrum antiepileptic drug used to treat various types of seizures. Although visual hallucinations have not been reported as an adverse effect of this agent, we describe three patients who experienced complex visual hallucinations and altered mental status after zonisamide treatment was begun or its dosage increased. All three had been diagnosed earlier with epilepsy, and their electroencephalogram (EEG) findings were abnormal. During monitoring, visual hallucinations did not correlate with EEG readings, nor did video recording capture any of the described events. None of the patients had experienced visual hallucinations before this event. The only recent change in their treatment was the introduction or increased dosage of zonisamide. With either discontinuation or decreased dosage of the drug the symptoms disappeared and did not recur. Further observations and reports will help clarify this adverse effect. Until then, clinicians need to be aware of this possible complication associated with zonisamide.

Adolescent↗
PubMed1987

Zonisamide enhances slow sodium inactivation in Myxicola.

In voltage-clamped Myxicola giant axons Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) caused a hyperpolarizing shift in the steady-state fast inactivation curve and retarded recovery from fast and slow Na+ inactivation. The effects of Zonisamide on steady-state fast inactivation could be described assuming a single binding site with a dissociation constant of 12 microM. Slow inactivation was significantly more sensitive, with a Kd of 1 microM from both steady-state and kinetic data. While these results account for anticonvulsant activity, the differential sensitivity suggests Zonisamide may also be useful in studies of the slow inactive state of the Na+ channel.

Animals↗
PubMed1990

Effect of a novel anticonvulsant, zonisamide (AD-810, CI-912), in an experimental model of photosensitive epilepsy.

The effects of a novel anticonvulsant, zonisamide (3-sulfamoylmethyl-1,2-benzisoxazole), on photically induced seizures were studied in the lateral geniculate-kindled cat. Zonisamide was found to reduce the behavioral severity of seizure responses to photic stimulation in a dose-related manner. This anticonvulsant effect was only observed with doses that caused behavioral toxicity, but anticonvulsant action outlasted behavioral effects. The present results suggest that zonisamide may be effective in the treatment of human photosensitive epilepsy.

Animals↗
PubMed1994

Regional distribution of 14C-zonisamide in rat brain.

Zonisamide (1,2-benzisoxazole-3-methane sulfonamide) is a new antiepileptic drug developed in Japan. This compound was proven to possess a strong inhibitory effect on convulsions of cortical origin, whether induced by electric or chemical stimuli. Regional distribution of 14C-zonisamide was investigated in rat brain using autoradiography. A high uptake of 14C activity was observed in the cerebral cortex and the midbrain. A pair-match analysis of primary motor cortex versus primary sensory cortex revealed a slightly higher uptake in primary motor cortex. In the cerebellum, a higher uptake was observed in the cortex than medulla. Sagittal section analyses revealed that a high uptake of 14C activity was observed in the cerebral cortex and colliculus, and a moderate uptake was seen in the cerebellum, thalamus, hypothalamus, and striatal body, thus suggesting the distribution of 14C-zonisamide is similar to that of flunitrazepam and phenytoin.

Animals↗
PubMed2005

Zonisamide for absence seizures.

This chart review investigated the efficacy and safety of zonisamide in 45 patients aged < or = 18 years with absence seizures. Of these patients, 23 (51.1%) achieved freedom from absence seizures. Two patients discontinued zonisamide, 1 for increased seizures and 1 for sleepiness and inefficacy. These data support the efficacy of zonisamide in treating absence seizures.

Adolescent↗
PubMed2004

Successful use of zonisamide for central poststroke pain.

UNLABELLED: We present 2 patients with severe and intractable central poststroke pain (CPSP) after right posterolateral thalamic infarcts who were successfully treated with zonisamide. The mechanism of action was presumed to be the suppression of overacting thalamic relay neurons by blockade of low voltage-activated calcium channel or by increasing gamma-aminobutyric acid (GABA) release. Zonisamide can be one of the therapeutic options for severe CPSP and might provide an insight into the pathogenesis of CPSP. PERSPECTIVE: The blockade of T-type VGCC or the increase in GABA release caused by zonisamide presumably suppresses abnormal activities of thalamic sensory neurons.

Anticonvulsants↗
PubMed2004

Clinical efficacy of zonisamide in childhood epilepsy after long-term treatment: a postmarketing, multi-institutional survey.

Postmarketing data about the effectiveness of zonisamide in childhood epilepsy was collected from 759 children with various forms of epilepsy (ages 3 months-15 years) to compare the long-term efficacy of zonisamide in the treatment of epilepsy in intellectually normal versus intellectually disabled children. The follow-up period was 6 months-3 years; 291 children (245 intellectually normal, 46 intellectually disabled) received zonisamide as monotherapy. The remaining patients received additional antiepilepsy drugs (AEDs); mean numbers of additional AEDs were 1.6 and 2.9 for intellectually normal and intellectually disabled groups, respectively. Effectiveness could not be evaluated in 30 of the 759 patients because of very rare or irregular seizure frequency. In the 729 patients evaluated, 78% of intellectually normal patients and 43% of intellectually disabled patients showed > or =50% reduction in the number of seizures (P < 0.001). Improvement rates seen in the intellectually normal group were almost the same for patients with generalized (82%) and partial (77%) epilepsies, whereas in the intellectually disabled group, the improvement rate was higher for partial (50%) than generalized (36%) epilepsies (P < 0.01). These results are consistent with the known phenomenon that intellectually disabled children are likely to have more intractable seizures than children with normal intelligence.

Adolescent↗
PubMed1997

Micellar electrokinetic capillary chromatography for therapeutic drug monitoring of zonisamide.

The simultaneous determination of zonisamide, a new type of antiepileptic drug, and the typical antiepileptic drugs phenobarbital, phenytoin and carbamazepine in human serum was developed using micellar electrokinetic capillary chromatography (MECC) with a diode array detector. A high correlation was revealed between the zonisamide levels in human serum obtained by MECC and those obtained by high-performance liquid chromatography (r=0.981). The serum levels of phenobarbital, phenytoin and carbamazepine determined by MECC were almost equal to those obtained by fluorescence polarization immunoassay. The reproducibility of separation and quantification with MECC analysis was appropriate for the intra- and inter-day assay coefficients. Therefore, the MECC method established here could provide a simple and efficient therapeutic drug monitoring method for antiepileptic drugs in patients, especially those treated with a combination of zonisamide and other antiepileptic drugs.

Anticonvulsants↗
PubMed1997

Heat stroke-like episode in a child caused by zonisamide.

A 2-year-old mentally retarded boy with frontal lobe epilepsy presented with an episode that resembled heat stroke during the administration of zonisamide. He developed hyperpyrexia with oligohidrosis and central neurological symptoms, including, chorea-like involuntary movements, resting tremor, and cogwheel rigidity. A sweat test using pilocarpine iontophoresis revealed a marked reduction in the sweat response, which suggested a postganglionic sweating dysfunction. A skin biopsy examined by light and electron microscopy showed no morphological abnormality in the sweat glands. The oligohidrosis caused by zonisamide was reversible in that the patient regained the ability to sweat within 2 weeks of the cessation of drug administration. Children receiving zonisamide should be monitored for oligohidrosis and the development of neurological symptoms associated with an elevation of body temperature.

Anticonvulsants↗
PubMed2000

Predictive value of acetylcholine stimulation testing for oligohidrosis caused by zonisamide.

We studied 16 patients for whom zonisamide was newly prescribed. Acetylcholine stimulation testing was performed about 1 month after zonisamide was initiated. Oligohidrosis occurred in none of the four with a normal response and in four of the 12 with a decreased response. Acetylcholine stimulation testing predicted oligohidrosis with a sensitivity of 1 and a false-positive rate of 0.67. The acetylcholine stimulation test was sensitive in detecting oligohidrosis caused by zonisamide, although the false-positive rate was high.

Acetylcholine↗
PubMed2000

Successful zonisamide treatment for infants with hypsarrhythmia.

We determined that zonisamide was effective in three epileptic infants with hypsarrhythmia. Two patients had the electroencephalographic pattern of hypsarrhythmia associated with developmental delay but lacked the characteristic tonic spasms. A third patient exhibited the typical triad of infantile spasms but had a poor general condition requiring controlled ventilation. We therefore chose zonisamide instead of adrenocorticotropin for these patients. Our data suggest that zonisamide may be a useful treatment in patients falling short of the diagnostic triad of infantile spasms or complicated by a poor overall medical condition.

Anticonvulsants↗
PubMed2006

An open prospective study of zonisamide in acute bipolar depression.

OBJECTIVE: To examine the effectiveness and safety of zonisamide in the treatment of acute bipolar depression. METHODS: An open-label, prospective, nonrandomized, 8-week study conducted in bipolar outpatients (type I, type II, or not otherwise specified) with depressive symptoms. No patient was manic or mixed at study entry. Previous treatments were continued unchanged, but no new treatments were allowed. Montgomery Asberg Depression Rating Scale and the Mania Rating Scale from the Schedule of Affective Disorders and Schizophrenia-Change Version were used. RESULTS: Twenty patients (10 men, 10 women) with bipolar disorder (17 type I, 2 type II, 1 NOS), aged 38.1 +/- 8.81 years, received zonisamide at mean dose of 222.5 +/- 85.1 mg/d. Mean Montgomery Asberg Depression Rating Scale scores improved significantly from baseline to endpoint (mean difference = -8.4, 95% confidence interval [4.1, 12.6], P = 0.001). Ten patients (50%) terminated early due to adverse effects, mostly side effects including nausea/vomiting, cognitive impairment, and sedation. One patient experienced increased suicidal ideation, and one patient experienced hypomania. CONCLUSIONS: This study suggests improvement of depressive symptoms in this sample with 8 weeks of open-label zonisamide treatment.

Acute Disease↗
PubMed1988

Progressive myoclonus epilepsy treated with zonisamide.

Two patients with progressive myoclonus epilepsy of the Unverricht-Lundborg type and with intractable seizures in spite of standard anticonvulsant regimens were treated with zonisamide. After zonisamide therapy was initiated, both had a marked decrease in seizure frequency and significant improvement of functioning. Serum zonisamide concentrations were 43 and 27 micrograms/ml, respectively, with doses of 8.8 and 10.5 mg/kg/d. Both patients also continue to receive valproic acid and a benzodiazepine.

Adult↗
PubMed2007

Zonisamide for bipolar depression.

In recent years, research into bipolar depression has increased. Each year, more studies are published using different agents to treat this condition. In addition to effectiveness and tolerability, bipolar depression research has sought agents that do not induce cycling or mania. This paper evaluates an open-label pilot study on zonisamide for bipolar depression that examined the effectiveness and tolerability of this agent while observing for any switch to mania. Zonisamide was found to have a very low switch rate and modest effectiveness. However, a high dropout rate was observed--mostly due to side effects. Until further research is available, zonisamide is not recommended as a first-line treatment for bipolar depression.

Bipolar Disorder↗
PubMed2004

Zonisamide: newer antiepileptic agent with multiple mechanisms of action.

Zonisamide (Zonegran, Eisai, Inc.) is a broad spectrum antiepileptic drug indicated for use as adjunctive therapy in the treatment of partial seizures. Zonisamide has multiple mechanisms of action, which may explain widespread reports of its utility in focal epilepsy and generalized epilepsy, and for nonseizure disorders such as headache and neuropathic pain. Zonisamide has been available in Japan since 1989 and became available in the USA in 2002. The rights to this drug in North America and Europe were recently acquired by Eisai Co. A review of the chemical properties, pharmacokinetics, metabolism, potential mechanisms of action, efficacy in seizure and nonseizure disorders, and tolerability was therefore thought to be timely.

Animals↗
PubMed1996

The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on topiramate, zonisamide and tiagabine.

Following the introduction of felbamate, gabapentin, lamotrigine, oxcarbazepine and vigabatrin in the early 1990s, other new antiepileptic drugs have been advancing in clinical development. Those most extensively evaluated to date include topiramate, zonisamide and tiagabine. Topiramate, licensed recently in the UK, acts multifactorially through the blockade of sodium channels and kainate/AMPA receptors, enhancement of gamma-aminobutyric acid (GABA)ergic transmission and inhibition of carbonic anhydrase. It is well absorbed from the gastrointestinal tract and negligibly bound to plasma proteins. When used as a monotherapy, topiramate is eliminated primarily in the urine in an unchanged form with a half-life of 20 to 30 hours; elimination is faster in patients receiving concurrent medication with enzyme-inducing anticonvulsants, in whom the extent of biotransformation becomes more prominent. Zonisamide, which has been commercially available in Japan for some years, also has a multifactorial mode of action, possibly involving the blockade of sodium channels, T-type calcium channels and inhibition of carbonic anhydrase. It is rapidly absorbed, 50% bound to plasma proteins and is eliminated predominantly by biotransformation; zonisamide has a half-life of 50 to 70 hours in monotherapy patients, or 25 to 35 hours in patients comedicated with enzyme-inducing anticonvulsants. Tiagabine, a nipecotic acid derivative which inhibits GABA reuptake, is rapidly and completely absorbed after oral intake. It is highly (96%) bound to plasma proteins and it is eliminated primarily by cytochrome P450 3A-mediated oxidation, with a half-life of about 7 hours in healthy volunteers. Tiagabine metabolism is also enhanced by concurrent medication with enzyme-inducing anticonvulsants, resulting in a need to use dosages larger than those required in monotherapy or valproic acid (sodium valproate)-treated patients. Additional investigational antiepileptic agents included in this article are rufinamide (CGP 33101), fosphenytoin, levetiracetam, losigamone, remacemide and stiripentol. All these drugs have undergone early characterisation with respect to pharmacokinetic features and interaction potential.

Anticonvulsants↗
PubMed2003

[A five-year-old girl with epilepsy showing forced normalization due to zonisamide].

A case of forced normalization in childhood is presented. When zonisamide was administered to a five-year-old girl with intractable epilepsy, disappearance of seizures was accompanied by severe psychotic episodes such as communication disturbance, personal relationship failure, and stereotyped behavior, which continued after the withdrawal of zonisamide. These symptoms gradually improved by administration of fluvoxamine, however epileptic attacks reappeared. Although most patients with forced normalization are adult and teenager, attention should be paid to this phenomenon as adverse psychotic effects of zonisamide even in young children. Fluvoxamine may be effective for the symptoms.

Anticonvulsants↗
PubMed1992

[Zonisamide induced tremor--report of two cases].

Zonisamide is a new antiepileptic drug which has a wide range of antiepileptic efficacy. This drug is becoming widely to be used for patients with refractory epilepsies. The author reports two patients who developed resting and postural hand tremor after administration of zonisamide. The tremor was confined to the upper extremities and was enhanced with the emotional stress. The tremor has 4-5 Hz frequency and was severe enough to disturb their daily activities. Mild cogwheel rigidity was seen, but neither akinesia nor gait disturbance was recognized. The symptoms disappeared completely after cessation of the drug. This side effect should always be kept in mind in the treatment with zonisamide.

Adult↗