Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topiramate is a recently licensed and marketed antiepileptic drug in the UK for use as add-on therapy for refractory partial epilepsy. It has multiple modes of action involving voltage-dependent sodium channels, GABA receptors and glutamate receptors. Topiramate has very favourable pharmacokinetics as it is primarily excreted unchanged. Its metabolism is, however, increased by enzyme inducers, and it can inhibit the metabolism of phenytoin in some patients. Its efficacy as adjunctive treatment in refractory partial epilepsy in adults appears good, over 40% of patients have a 50% or greater reduction in seizure frequency when topiramate is added to their regime with up to 7% becoming seizure free. The main adverse events are ataxia, impaired concentration, confusion, dizziness, fatigue, parasthesia, somnolence and "thinking abnormal'. Most of these occurred during rapid titration. During long-term treatment, weight loss also occurred and nephrolithiasis occurred in 1.5% of patients receiving topiramate. Topiramate is a useful and well-tolerated addition to our treatment of refractory epilepsy, but it should be titrated slowly in order to avoid adverse events.
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PMID:Topiramate: a new antiepileptic drug for refractory epilepsy. 890 21

Topiramate is a new antiepileptic drug which has recently become available in the United States and in a number of European countries. Pharmacological studies suggest that its mode of action is multifactorial and involves blockade of voltage-dependent sodium channels, potentiation of GABAergic transmission and inhibition of excitatory pathways through an action at AMPA receptor sites. Carbonic anhydrase inhibiting properties have also been demonstrated but they are considered not to be relevant to anticonvulsant activity. Topiramate is well absorbed from the gastrointestinal tract, peak plasma levels being usually attained in 2-3 hours. The drug is negligibly (9-17%) bound to plasma proteins and is eliminated partly by renal excretion in unchanged form and partly by oxidation and hydrolysis. In healthy volunteers, the half-life is about 20-30 hours, but elimination rate is accelerated in patients taking concomitant enzyme inducing drugs such as phenytoin, carbamazepine and barbiturates. Topiramate has no major effects on plasma levels of concurrent anticonvulsants, except for a rise in plasma phenytoin in occasional patients. In double-blind add-on trials in refractory partial epilepsy, a significant reduction in seizure frequency has been demonstrated in over 40% of topiramate-treated patients (vs about 10% of those treated with placebo), a response rate which compares favourably with that observed with other new antiepileptic drugs. Dosages found to be effective in add-on controlled trials range between 200 and 1000 mg day-1, although most patients are likely to benefit from receiving 400 mg day-1 or less. Preliminary data suggest that topiramate may be effective also in generalized epilepsies, but this needs to be confirmed in prospective studies. The most common adverse effects of topiramate are CNS-related and include dizziness, fatigue, visual disturbances, ataxia, mental slowing and impaired concentration. Paresthesias, anorexia, weight loss and increased risk of nephrolithiasis have been also reported. Many of these effects are related to dose and/or to rate of dose titration. Based on these data, topiramate appears to be a valuable new drug, whose main current indication is in the add-on management of refractory partial and secondarily generalized seizures. Studies on its potential-value as monotherapy are in progress.
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PMID:A pharmacological and clinical review on topiramate, a new antiepileptic drug. 926 38

Topiramate is a new antiepileptic drug, which is not yet marketed in Germany. The anticonvulsive activity is probably mediated by sodium-channel blockade combined with gabaergic and weak antiglutamatergic properties. We investigated 23 patients with partial seizures in this open prospective study. The efficacy was analysed under stable concurrent antiepileptic drugs. Two of the patients became seizure free. Ten patients had a reduction of seizure frequency of at least 50%. The responder rate was 57%. The maximum daily dosages were 400 to 850 mg. Side-effects without relationship to dose were nervousness and aggression. In two patients an psychotic episode occurred. Dose-related side-effects were ataxia, dizziness, somnolence and dysarthria. This study is underlining that topiramate is efficacious in the treatment of partial onset seizures but also associated with a narrow therapeutic width.
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PMID:[Topiramate--an effective new anticonvulsant. An open prospective study]. 944 Dec 57

The antiepileptic drug (AED) topiramate is a monosaccharide derivative with a sulfamate functionality. It modulates voltage-dependent sodium conductance, potentiates gamma-aminobutyric acid-evoked currents, and blocks the kainate/AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) subtype of the glutamate receptor. Topiramate is rapidly absorbed and has linear, proportional, steady-state pharmacokinetics. It has no known clinically significant effect on plasma levels of carbamazepine, valproic acid, or phenobarbital, although it may increase plasma concentrations of phenytoin in some patients. When topiramate is used with hepatic enzyme-inducing AEDs, its plasma concentrations are approximately 50% lower than when it is administered alone. The efficacy of topiramate 200 to 1000 mg/d administered in two divided doses as adjunctive therapy for partial-onset seizures was investigated in five double-masked, placebo-controlled trials. The median percentage reduction in average monthly seizure frequency from baseline was 12% for placebo, compared with 30% for the 200-mg/d group and 48% for the 400-mg/d group. At a dosage of 400 mg/d, a seizure reduction of 75% or greater was seen in 22% of topiramate patients, compared with 7% of those receiving placebo; up to 9% of topiramate patients, compared with none of those receiving placebo, became seizure free. Although little additional efficacy was seen at dosages of 600, 800, and 1000 mg/d, dosing should be individualized, because some patients may respond to higher dosages. When topiramate is combined with other AEDs, the most common side effects at dosages of 200 to 400 mg/d are somnolence, dizziness, ataxia, psychomotor slowing, hesitant speech, and wordfinding difficulties. Most patients who experienced adverse events during the first 8 weeks of the trials no longer experienced them by their last visit. Although there was a 1.5% incidence of renal stones that may be associated with carbonic anhydrase inhibition, more than 75% of patients experiencing a stone continued on therapy.
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PMID:Topiramate: a review of preclinical, pharmacokinetic, and clinical data. 944 41

Six studies are cited to demonstrate that topiramate is effective as adjunctive therapy for refractory partial-onset seizures in adults. Subsequent studies indicate that topiramate is also effective as monotherapy in adults and as adjunctive therapy for partial-onset seizures in children, tonic-clonic seizures of nonfocal origin in children and adults, and drop attacks in Lennox-Gastaut syndrome. Adverse effects for adults and children included dizziness, fatigue, ataxia, confusion, somnolence, nephrolithiasis, paresthesia, and weight loss. More adverse effects were observed at higher doses. Topiramate exhibits rapid absorption, long duration of action, and minimal interaction with other antiepileptic drugs.
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PMID:Topiramate. 1053 Jun 97

Twenty patients of either sex, with refractory partial epilepsy with or without secondary generalisation were entered in an open label study to evaluate the efficacy and safety of topiramate in them. Topiramate was used as an adjunctive therapy with an initial starting dose of 50 mg/day. The dose was then titrated upwards with increments of 50 mg per week, till a time the most effective and the best tolerated dose was reached. This most effective/tolerated dose was then continued for 6 months. Of the 17 patients entering the maintenance phase, 4 patients (24%) became seizure free, while a total of 14 patients (83%) out of 17 cases responded with a reduction in monthly seizures rate by 50% or more. Mean reduction of 68.9% was observed in monthly seizure rate during the maintenance phase. The median effective dose of topiramate was 600 mg per day. Five patients dropped out of the study due to adverse events such as anxiety, aggressiveness, rash, lethargy, etc. The central nervous system (CNS) related side effects such as dizziness, headache, and tremor were reported, which are commonly seen with other presently available antiepileptics like carbamazepine, phenytoin sodium, sodium valproate, etc, as well. Most adverse events, however, were mild and transient and did not interfere with the day to day activity of the patients. Topiramate was not associated with any abnormality in laboratory or neurological examination findings. The excellent response with topiramate therapy in Indian patients, uncontrolled with the available antiepileptics, as well as its good safety profile endorse the international efficacious and safe image of topiramate.
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PMID:Topiramate: a new safe and effective antiepileptic. 1188 61

The objective of this paper was to determine if topiramate is effective as treatment for bipolar spectrum disorders in a naturalistic setting. All charts of outpatients treated with topiramate (n = 76) were reviewed, and clinical response was assessed retrospectively using the Clinical Global Impressions Scale for Improvement. Mild improvement was seen in 47% (n = 36) and moderate-to-marked improvement in 13% (n = 10). Responders received a higher mean dose (180 mg/day) than did nonresponders (83.2 mg/day, p = 0.002). Topiramate dose was also higher in those who lost weight (138.3 mg/day) than in those who did not (70 mg/day, p = 0.007). Weight loss was experienced by 50% of the sample, with a mean loss of 14.2 lbs. Side effects were reported by 82% (n = 62) of the population, including cognitive effects, sedation, parasthesias, nausea, insomnia, headache, and dizziness. Adverse effects led 36% (n = 27) of the total sample to discontinue treatment with topiramate. Topiramate led to significant weight loss in about half of this bipolar population, while also improving mood symptoms at least mildly in most patients. Topiramate response and weight loss were both dose-related, with efficacy, in particular, associated with higher doses (mean = 180 mg/day) than frequently used in current clinical practice.
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PMID:Topiramate treatment of bipolar spectrum disorders: a retrospective chart review. 1195 60

Topiramate (Topamax), an effective seizure disorder treatment, received additional FDA approval for prevention of migraine headaches in August 2004 and has gained attention for its off-label uses, including psychiatric and eating disorders, neuropathic pain, and alcohol and drug dependency. Side effects of sedation, dizziness, ataxia, speech difficulty, nystagmus, paresthesia, and metabolic acidosis are described. The manufacturer reports that tolerance to the antiseizure properties does not develop. With its established efficacy for epilepsy treatment and its increased use for other disorders, topiramate-positive findings are more common in death-investigation and human-performance casework. To evaluate the role of topiramate, we reviewed all topiramate-positive cases from our laboratory between 1998 and 2004, which constituted 132 cases (63 death investigations, 68 suspected impaired drivers, and 1 sexual assault case). The subjects were predominantly female (69%) with a mean and median age of 42. Blood topiramate concentrations ranged from 1 to 180 mg/L (median 6.4 mg/L, mean 8.4 mg/L), and 94% were positive for at least one additional drug. There was evidence of psychomotor impairment in some drivers with blood concentrations within the normal therapeutic range, and deaths attributed to topiramate alone occurred at concentrations as low as 50 mg/L.
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PMID:Topiramate-positive death-investigation and impaired-driving cases in Washington State. 1713 58

The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS showed improvement with the topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse events were reported by 75% of topiramate-treated patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double-blind, placebo-controlled trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of chronic migraine, even in the presence of medication overuse.
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PMID:Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. 1744 71

An open-label, observational prospective study assessed the effectiveness of topiramate (TPM) as add-on therapy. A total of 450 patients aged 12 and above with a diagnosis of epilepsy and at least one epileptic seizure during the 12-week retrospective baseline were to be documented. After baseline evaluation, topiramate was added. Ninety-five percent of patients had at least one baseline AED, most commonly Carbamazepine (53%) or Valproate (34%). In 5% TPM was started in monotherapy. Topiramate dose titration and target dose was determined by clinical response and side effect profile. Patients were intended to be followed for a total of 1 year which included 6 visits during which seizure frequency, adverse events, weight as well as clinical global impression were recorded. During the 12 weeks retrospective baseline, a median of 2.8 seizures per month were recorded which reduced significantly to 0.7 per month during the complete treatment phase (p < 0.0001). Seventy-two percent of patients had a > or =50% seizure reduction. Ten percent of patients were seizure free during the study. The most commonly reported adverse events were difficulties with memory (4.2%), somnolence (3.6%), and dizziness (2.7%). Overall, topiramate was well tolerated, and only 5% of patients discontinued treatment due to an adverse event. Retention in the study was higher than previously reported during randomized, dose controlled studies and is likely due to individualized doses as well as slower titration used.
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PMID:Topiramate in add-on therapy: results from an open-label, observational study. 1754 44


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