To evaluate the risk of oral cleft and major congenital malformation occurrence in infants born to women exposed to topiramate in their first trimester of pregnancy compared with women who used other anti-epileptic drugs or those with disease states in which topiramate may have been used.
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Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents including selective serotonin reuptake inhibitors, antiepileptic drugs, and opioid antagonists are shown to be effective in the short-term treatment of PG. The use of a wide range of pharmacological treatments for PG is consistent with the observation that PG shares features of obsessive-compulsive spectrum disorders, impulse control disorders, and addictive disorders. The aim of the study is to assess the rate of relapse in treatment-responder pathological gamblers after discontinuation of the active treatment.
Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.
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The present article describes two unrelated cases of progressive myoclonic epilepsy (PME) of the Lafora's disease and Unverricht-Lundborg types who were treated with topiramate (TPM) as add-on therapy for their myoclonus. After the initiation of topiramate therapy both cases responded with marked decrease in myoclonic seizure frequency and improvement of quality of life. Topiramate appears to be a useful alternative agent in cases of PME and could be consider for adjunctive therapy.
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Epilepsy in brain tumor patients is often refractory to pharmacological treatments and can complicate the therapeutic management of these patients. We conducted a prospective, observational study. The aim of this study was to investigate the efficacy and tolerability of topiramate (TPM) in brain tumor associated epilepsy. We studied 47 patients with brain tumors and epilepsy. The entire group was administered AEDs. TPM was the first therapeutic choice in 14 patients, while in the remaining 33 patients previous AEDs were modified and TPM was introduced due to side effects or inefficacy of the first drug. Follow-up ranged from 3 to 48 months (mean 16.5 months). Considering the final follow-up of each patient who assumed TPM for at least 3 months, we observed 45 patients: 25 were seizure free (55.6%), 9 had a reduction of seizure frequency (SF) higher than 50% (20%) and 11 were stable (24.4%). TPM responder rate was 75.6%. Three patients (6.4%) discontinued TPM for severe side effects (1 after 4 months and 2 after 1 month) and 4 (8.5%) had mild and reversible side effects. In the group of patients who had been in therapy with other AEDs prior to entering the study (n = 33), 19 patients had side effects (57.6%). During follow-up, the haematological parameters were in the normative ranges. Tumor-related seizures are difficult to control with AEDs; the precise reasons for this difficulty are not yet clear. Using TPM, we obtained good seizure control with a low incidence of side effects.
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Given the lack of pharmacogenetic research on response to AUD medication in ethnic minority populations and the mixed results, there is a critical need for future studies among individuals of different ancestries. More efforts should be devoted to standardizing procedures such that results can be more readily integrated into a body of literature that can directly inform clinical practice.
The microsomal MMCA activity was lower in the PTZ group than in control although the MMCA activities were higher in the treatment group than in PTZ group. Brain cortex total calcium levels, the hippocampus NMDAR 2A and 2B subunit concentrations were higher in the PTZ group than in control although their concentrations were decreased by TOP50 and TOP100 administration. Total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations were higher in TOP100 group than in TOP50 group.
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Of the 88 assessed records, 47 were eligible. We included patients that met the diagnostic criteria for VM and excluded those whose medical records were illegible and those of patients with other disorders causing dizziness and/or headache that did not meet the 2012 criteria for VM. 80.9% of the patients showed improvement with prophylaxis (p<0.001). Amitriptyline, Flunarizine, Propranolol and Topiramate improved vestibular symptoms (p<0.001) and headache (p<0.015). The four drugs were effective in a statistically significant manner. There was a positive statistical association between the time of vestibular symptoms and clinical improvement. There was no additional benefit in hypertensive patients who used antihypertensive drugs as prophylaxis or depressed patients who used antidepressants in relation to other prophylactic drugs. Drug association did not show statistically significant results in relation to the use of a single drug.
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In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥ 50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated.
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Both levetiracetam and topiramate significantly decreased migraine frequency, compared with placebo. MO patients displayed increased alpha-band phase synchronization as an effect of stimulus frequency; on the other hand the stimuli had an overall desynchronizing effect on control subjects. The phase synchronization index separates the two stages, before and after the treatment, only for levetiracetam, at stimulus frequencies of 9, 18, 24 and 27 Hz.
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This article highlights the proceedings of a symposium presented at the 27th Annual Scientific Meeting of the Research Society on Alcoholism in Vancouver, British Columbia, Canada, June 29, 2004. The organizers and co-chairs were Bankole A. Johnson, MD, PhD, and Robert M. Swift, MD, PhD. The presentations included (1) Introduction, by Bankole A. Johnson; (2) Safety, Tolerability, and Efficacy of gamma-Hydroxybutyric Acid and Baclofen in the Treatment of Alcohol Addiction, by Giovanni Addolorato; (3) Safety of Gabapentin in Treating Alcoholism, by Hugh Myrick; (4) New Data on the Safety and Effectiveness of Topiramate in the Treatment of Alcohol Dependence, by Bankole A. Johnson; (5) Evaluating the Risk of Benzodiazepine Prescription to Alcohol-Dependent Individuals, by Domenic A. Ciraulo; and (6) Safety and Efficacy of GABAergic Agents in Treating Alcoholics: Discussion, by Robert M. Swift.
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We measured the cortical susceptibility to SD and ischemic depolarizations, and determined tissue and neurological outcomes after middle cerebral artery occlusion in wild-type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing.
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Dysaesthetic pain is a common neuropathic pain in patients with multiple sclerosis. Both tricyclic antidepressants (i.e., amitriptyline and duloxetine) and antiepileptic drugs (i.e., carbamazepine, gabapentin and pregabalin) represent first-line treatment of neuropathic pain. However, topiramate, an antiepileptic drug, also demonstrated clinical efficacy in these patients. In this report we describe the case of a 42-year-old woman with an 8-year history of multiple sclerosis who developed dysaesthetic pain in the lower limbs, and was successfully treated with topiramate at a final dose of 150 mg/day. About 8 months after beginning topiramate treatment, the patient had not shown any dysaesthetic pain, and no adverse events related to topiramate had been recorded.
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For now, the best strategy for the treatment of suspected vestibular migraine patients is dietary/lifestyle modification, antinausea/antiemetics for acute vertigo, and preventive medication for patients who have continued disruptive symptoms. Patients with vestibular migraine should be monitored regularly for the development of latent audiovestibular end-organ disease.
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All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
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Thalidomide was synthesized more than 50 years ago as hypnotic sedative with unique pharmacologic properties. Recently, we have described a notorious anticonvulsant effect of thalidomide on pentylenetetrazole-induced seizures. Here, we report the results of thalidomide administration on amygdaloid kindling. A total of 100 male Wistar rats were implanted with brain electrodes in the basolateral amygdaloid nucleus and the sensory motor cortex. After surgery the animals received a daily electric stimulus through the amygdaline electrode (500 μA intensity, 60 Hz frequency, 1 ms duration) until seizures appeared. The following treatment groups were made: (a) controls; (b) rats treated daily with thalidomide (10 mg/kg) or with topiramate (80 mg/kg); (c) rats treated with different doses of thalidomide. Significant reduction in the after-discharge and retard of behavioral stages were observed in rats treated with thalidomide or with topiramate as compared with controls (p<0.01): Also, a similar anticonvulsant outcome of thalidomide therapy was obtained with doses of either 2.5, 5, 10 or 50 mg/kg; at 100 mg/kg all epileptic activity was suppressed. Anticonvulsant efficacy of thalidomide was superior in most parameters than that obtained with topiramate. In amygdaloid kindling, which simulates human epilepsy characterized by focal seizures secondarily generalized, low doses of thalidomide display strong anticonvulsant properties.
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About 15% of patients who undergo adjustable gastric banding (AGB) have difficulty losing weight due to, among other factors, the development or maintenance of binge eating disorder. Topiramate is an anticonvulsive drug with proven good results in controlling binge eating episodes. The objective of this study was to analyze the effect of topiramate in patients with AGB.
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We propose an exploratory approach, using more flexible smoothing mixed effects models, more accurately to characterize the temporal patterns of the drinking data. We estimated the trajectories of the treatment arms for data sets from 2 sources: a multisite topiramate study, and the Combined Pharmacotherapies (acamprosate and naltrexone) and Behavioral Interventions study.
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Atypical antipsychotics have been associated with weight gain. This study examines the efficacy of adjunctive topiramate in patients with schizophrenia and schizoaffective disorder with antipsychotic-induced weight gain.
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This heuristic may be helpful in producing faster symptom resolution, fewer side effects, and increased compliance.
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Antiepileptic drugs have been used for treating different types of neuropathic pain, and sometimes fibromyalgia. Our understanding of quality standards in chronic pain trials has improved to include new sources of potential bias. Individual Cochrane reviews using these new standards have assessed individual antiepileptic drugs. An early review from this group, originally published in 1998, was titled 'Anticonvulsants for acute and chronic pain'. This overview now covers the neuropathic pain aspect of that original review, which was withdrawn in 2009.
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A non-anion gap acidosis can be induced by topiramate, causing symptomatic dyspnea and confusion.
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Available AEDs to prophylactically treat migraine are few but of robust clinical efficacy. Special care needs to be exerted with respect to their side effects. Future research is needed for a better understanding of their mechanisms of action in migraine. Such research has the potential of providing some insight into the pathophysiology of migraine.
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Bipolar electrical stimulation was applied to the OB or AMG every day until generalized seizure was achieved. Antiepileptics (carbamazepine, sodium valproate, zonisamide, clobazam, and topiramate), which are used for complex partial epilepsy or secondary generalized epilepsy in clinical practice, were orally administrated to kindled rats.
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Future long-term studies with larger sample sizes are needed to investigate the clinical utility of anticonvulsants for posttraumatic stress disorder treatment.
The treatment of Lennox-Gastaut syndrome has been improved for some patients by the introduction of adjunctive therapy with newer anticonvulsants such as lamotrigine and topiramate and the availability of vagal nerve stimulation and the re-emergence of the use of the ketogenic diet in recent years. The place of standard anticonvulsants and the role of callosotomy needs to be re-evaluated in view of the new developments. Although recommendations for the treatment of patients with Lennox-Gastaut syndrome are difficult to make in the absence of direct head-on comparative trials, the following suggested treatment recommendations are based on the best evidence available. Medical treatment should start with valproic acid (sodium valproate) and be followed by adjunctive therapy with either lamotrigine or topiramate; clobazam can be added if necessary for better seizure control while trying to reduce the dose of the other anticonvulsants. If standard treatment does not achieve sufficient seizure control or proves to be intolerable, vagal nerve stimulation, ketogenic diet, felbamate, benzodiazepines such as clonazepam, and phenobarbital (phenobarbitone) are recommended as third-line choices. Further considerations include ethosuximide, methsuximide, corticotropin (adrenocorticotropic hormone) or corticosteroids, pyridoxine (vitamin B6) and vigabatrin. If adequate drug treatment and vagal nerve stimulation provide insufficient seizure control, partial callosotomy may be an option for the treatment of frequent, intractable and disabling drop attacks. These suggestions are based on the best evidence available and do not in any way exclude the use of other treatments if compelling individual risk-benefit considerations apply.
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Prader-Willi syndrome is a multisystem neurogenetic obesity disorder with behavioral manifestations, including hyperphagia, compulsive behavior, self-injury, and mild to moderate mental retardation. In an 8-week open-label study, we evaluated adjunctive therapy with the anticonvulsant topiramate in 8 adults with Prader-Willi syndrome. Appetite was measured by a 1-hour access to food four times throughout the study and quantified with a visual analogue scale. Topiramate did not significantly change calories consumed, Body Mass Index, or increase self-reported appetite. In addition, there were no significant changes in compulsions. Surprisingly, topiramate treatment resulted in a clinically significant improvement in the self-injury (i.e., skin-picking) that is characteristic of this syndrome. Potential benefits of topiramate for self-injury should be evaluated further in controlled trials.
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Topiramate (topamax) is an antiepileptic drug of the new generation that was first registered and introduced in clinical practice in 1995. Due to its effective clinical properties, the drug is used widely all over the world including Russia where it has been using since 1999. Topamax is a principally new antiepileptic drug (AED) with the unique mechanism of action, favorable pharmacokinetics, high efficacy and safety. During its existence, it is widely accepted as an AED of first choice for additional and initial treatment of many forms of epilepsy in children over 2 years old and adults including old patients of both sexes. The drug can be successfully used as monotherapy and as well as polytherapy in treatment of most severe and "catastrophic" epilepsies resistant to any previous treatment.
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A carbonic anhydrase (CA, EC 184.108.40.206) belonging to the γ-class has been cloned, purified and characterized from the Antarctic cyanobacterium Nostoc commune. The enzyme showed a good catalytic activity for the physiologic reaction (hydration of carbon dioxide to bicarbonate and a proton) with the following kinetic parameters, kcat of 9.5×10(5)s(-1) and kcat/KM of 8.3×10(7)M(-1)s(-1), being the γ-CA with the highest catalytic activity described so far. A range of aromatic/heterocyclic sulfonamides and one sulfamate were investigated as inhibitors of the new enzyme, denominated here NcoCA. The best NcoCA inhibitors were some sulfonylated sulfanilamide derivatives possessing elongated molecules, aminobenzolamide, acetazolamide, benzolamide, dorzolamide, brinzolamide and topiramate, which showed inhibition constants in the range of 40.3-92.3nM. As 1,5-bisphosphate carboxylase/oxygenase (RubisCO) and γ-CAs are closely associated in carboxysomes of cyanobacteria for enhancing the affinity of RubisCO for CO2 and the efficiency of photosynthesis, investigation of this new enzyme and its affinity for modulators of its activity may bring new insights in these crucial processes.
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Topiramate is an effective adjunctive treatment in bipolar refractory patients and the significant weight reduction effects may result in important medical risk reductions, and make topiramate attractive for some obese bipolar patients.