Dose Of Topiramate Research Articles

Topiramate modulates hippocampus NMDA receptors via brain Ca2+ homeostasis in pentylentetrazol-induced epilepsy of rats

Background: Increase in neuronal Ca2+, activation of hippocampus N-methyl-D-aspartate receptor (NMDAR) and defects in enzymes such as brain cortex microsomal membrane Ca2+-ATPase (MMCA) are thought to play a role in epilepsy. Topiramate (TOP) is a novel drug with broad antiepileptic effect, and its effect on brain cortex MMCA is not known. We investigated effects of TOP on pentylentetrazol (PTZ)-induced MMCA activity and NMDAR subunits in rat brain.Materials and methods: Thirty-two rats were randomly divided into four equal groups. The first group and second groups were used for the control and PTZ groups, respectively. 50 and 100 mg TOP were administered to rats constituting the third (TOP50) and fourth (TOP100) groups for 7 days, respectively. At the end of 7 days, all groups except the first received a single dose PTZ. Brain and hippocampus samples were taken at 3 hrs after PTZ administration.Results: 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.Conclusion: The two doses of TOP modulated MMCA activity, total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations in the epileptic rats.

Topiramate augmentation in patients with resistant major depressive disorder: A double-blind placebo-controlled clinical trial

Despite evolution of new antidepressant treatment, clinicians still encounter challenges in the treatment of depressed patients. Looking for new medications that can potentiate the effects of current antidepressants seems to be necessary. Our objective is to survey the efficacy of topiramate augmentation in resistant major depressive disorder (MDD). This augmentation trial was designed as an 8-week randomized, placebo-controlled, double-blind study. Fifty three patients with DSM-IV diagnosis of MDD who had failed to respond to at least 8 weeks of treatment with an adequate dose of one of the SSRIs (fluoxetine, citalopram or serteraline) were included in the study. Patients were randomized to receive a flexible dose of topiramate (100-200 mg/day) or placebo beside their current antidepressant medication for a period of eight weeks. Outcome measures were Hamilton Depression Scale (HAM-D) and Clinical Global Impression (CGI). 42 patients completed the study and there were 6 and 5 dropouts in topiramate and placebo groups, respectively. The topiramate group demonstrated significant improvement over the study period based on mean HAM-D score at week 8 compared to baseline (P = .000, Z = 3.699). Those receiving topiramate demonstrated to have a mean decrease of 32.0% in HAM-D score, compared to only 5.5% for those receiving placebo. Depressed mood, suicidality, insomnia (early, middle and late), agitation and anxiety symptoms were significantly improved in the topiramate group. Our double-blind placebo-controlled study demonstrated that topiramate augmentation potentiate the efficacy of selective serotonin reuptake inhibitors (SSRIs) in treatment of resistant major depressive disorder. Of note is that our study is preliminary and larger double-blind studies are needed to confirm the results.

Refractory topiramate-induced angle-closure glaucoma in a man: a case report

IntroductionTopiramate is a sulphonamide derivative indicated in the treatment of epilepsy and migraine. A known adverse affect is an idiosyncratic reaction that results in angle-closure glaucoma. We describe a patient with bilateral glaucoma related to topiramate that showed some unusual clinical features.Case presentationA 39-year-old Caucasian man presented with acute angle-closure glaucoma; he initially presented with intractable headaches after being treated with an escalating dose of topiramate. Clinical signs included elevated intraocular pressure that was initially refractory to treatment, shallow anterior chambers, and extensive bilateral choroidal effusions. After treatment with intravenous methylprednisolone, in conjunction with conventional glaucoma treatment, there was rapid reduction of intraocular pressure, gradual delayed resolution of the choroidal effusion and induced myopic shift; and eventually a good outcome without optic nerve damage.ConclusionThis case illustrates the importance of recognizing this entity in a non-ophthalmic setting and that intravenous methylprednisolone may be useful in the treatment of the condition when it is not responsive to conventional treatment. In addition, it is important to recognize that complete resolution of visual symptoms from the myopic shift may be delayed, despite normalization of intraocular pressure.

Topiramate dose effects on cognition

Topiramate (TPM), a broad-spectrum antiepileptic drug, has been associated with neuropsychological impairment in patients with epilepsy and in healthy volunteers. To establish whether TPM-induced neuropsychological impairment emerges in a dose-dependent fashion and whether early cognitive response (6-week) predicts later performance (24-week). Computerized neuropsychological assessment was performed on 188 cognitively normal adults who completed a double-blind, placebo-controlled, parallel-group, 24-week, dose-ranging study which was designed primarily to assess TPM effects on weight. Target doses were 64, 96, 192, or 384 mg per day. The Computerized Neuropsychological Test Battery was administered at baseline and 6, 12, and 24 weeks. Individual cognitive change was established using reliable change index (RCI) analysis. Neuropsychological effects emerged in a dose-dependent fashion in group analyses (p < 0.0001). RCI analyses showed a dose-related effect that emerged only at the higher dosing, with 12% (64 mg), 8% (96 mg), 15% (192 mg), and 35% (384 mg) of subjects demonstrating neuropsychological decline relative to 5% declining in the placebo group. Neuropsychological change assessed at 6 weeks significantly predicted individual RCI outcome at 24 weeks. Neuropsychological impairment associated with TPM emerges in a dose-dependent fashion. Subjects more likely to demonstrate cognitive impairment after 24 weeks of treatment can be identified early on during treatment (i.e., within 6 weeks). RCI analysis provides a valuable approach to quantify individual neuropsychological risk.

Topiramate Augmentation in Resistant OCD: A Double-Blind Placebo-Controlled Clinical Trial.

Glutaminergic dysfunction has been shown to be related to the pathphysiology of obsessive-compulsive disorder (OCD). Topiramate is an antiepileptic that inhibits glutaminergic action. The aim of this study is to evaluate the efficacy of topiramate augmentation in patients with treatment resistant OCD. This augmentation trial was designed as a 12-week randomized, placebocontrolled, double-blind study. Forty-nine patients suffering from OCD who had failed to respond to at least 12 weeks of treatment of an adequate and stable dose of a selective serotonin reuptake inhibitor (SSRI) were randomly allocated to receive topiramate or placebo plus their current anti OCD treatment. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the primary outcome measure. Treatment response was defined as 25 % or more decrease in scores of Y-BOCS. The mean dosage of topiramate was 180.15 mg/day (range 100-200 mg/day). Forty-one patients (20 of 24 in topiramate group; 21 of 25 in placebo group) completed the trial. The topiramate group showed significant improvement over the study period (mean Y-BOCS score at week 12 as compared with baseline: P=.000). Those receiving topiramate experienced a mean decrease of 32.0% in Y-BOCS score, compared with 2.4% decrease for those receiving placebo. Twelve patients in the topiramate group versus no patient in the placebo group were rated as responder. The results of our study demonstrated that topiramate may augment the therapeutic effect of SSRIs in treatment-resistant OCD patients. However, it should be noted that our study is preliminary and larger double-blind studies are needed to confirm these results.

Patients With and Without Prior Urolithiasis Have Hypocitraturia and Incident Kidney Stones While on Topiramate

To determine the effect of topiramate (TPM) on 24-hour urinary parameters in stone formers. TPM is frequently prescribed for epilepsy, migraine headaches, and eating disorders. Twelve stone-forming patients who were prescribed TPM between 2003 and 2008 were identified from our stone clinic. Of these, 9 patients (M:F, 4:5; 47 ± 7.1 y SEM) underwent a full metabolic workup (UroRisk Diagnostic Profile, Mission Pharmacal Reference Laboratory, San Antonio, TX) and were included for review. Parameters examined include duration and dose of the drug, 24-hour urine calcium, oxalate, citrate, volume, and pH. If available, urine parameters before taking TPM and after either stopping it or receiving potassium citrate therapy were recorded. Mean duration taking TPM was 17 ± 5.2 months (range, 3-43) months and median dose was 100 mg (range, 25-300) daily. Mean urinary citrate excretion was 136 ± 29 mg/d (range, 30-280) in all patients taking the drug. Three patients were either taken off the drug or placed on potassium citrate, resulting in a mean increase in urinary citrate of 374 mg/d (65%). TPM dosage correlated inversely with urinary citrate excretion (Pearson correlation coefficient = -0.73). TPM therapy is associated with a profound, dose-dependent decrease in urinary citrate, leading to increased lithogenic risk. This hypocitraturia persists even after long periods of taking the drug. Urologists should be aware of the stone-forming risk of this medication. Strategies to maintain therapeutic urinary citrate concentrations in patients on TPM are needed.

Pharmacokinetic–pharmacodynamic assessment of topiramate dosing regimens for children with epilepsy 2 to &lt;10 years of age

To identify and validate the efficacious monotherapy dosing regimen for topiramate in children aged 2 to <10 years with newly diagnosed epilepsy using pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation bridging. Several models were developed in pediatric and adult populations to relate steady-state trough plasma concentrations (C(min)) of topiramate to the magnitude of clinical effect in monotherapy and adjunctive settings. These models were integrated to derive and support the monotherapy dosing regimen for pediatric patients. A two-compartmental population PK model with first-order absorption described the time course of topiramate C(min) as a function of dosing regimen. Disposition of topiramate was related to age, body weight, and use of various concomitant antiepileptic drugs. The PK-PD model for monotherapy indicated that the hazard of time to first seizure decreased with increasing C(min) and time since randomization. Higher baseline seizure frequency increased risk for seizures. Age did not significantly influence hazard of time to first seizure after randomization to monotherapy. For adjunctive therapy, the distribution of drug and placebo responses was not significantly different among age groups. Based on the available PK-PD modeling data, the dosing regimen expected to achieve a 65-75% seizure freedom rate after 1 year for pediatric patients age 2-10 years is approximately 6-9 mg/kg per day. This analysis indicated no difference in PK-PD of topiramate between adult and pediatric patients. Effects of indication and body weight on PK were adequately integrated into the model, and monotherapy dosing regimens were identified for children 2-10 years of age.

Assessment of the Middle Dose of Topiramate in Comparison with Sodium Valproate for Migraine Prophylaxis: A Randomized-Double-Blind Study

Assessment of the Middle Dose of Topiramate in Comparison with Sodium Valproate for Migraine Prophylaxis: A Randomized-Double-Blind Study

Topiramate-induced myoclonus and psychosis during migraine prophylaxis

A case of topiramate-induced myoclonus and acute psychosis in a patient taking the recommended dosage of topiramate for migraine prophylaxis is reported. A 29-year-old Caucasian, wheelchair-bound woman with diplegic cerebral palsy and a history of migraines was admitted to the hospital after developing paranoid thoughts and episodes of myoclonus two weeks after an increase in her topiramate dosage (25 mg twice daily to 50 mg twice daily). Her physical examination upon admission was unremarkable, with the exception of a temperature of 38.2 degrees C. Diagnostic laboratory test values, including those of the cerebrospinal fluid, were within normal limits. During neurologic examination, arm jerking, lip smacking, and finger movements occurred spontaneously and unprovoked, and severe bilateral leg myoclonus with plantar stimulation was observed. The results of an ultrasound of her lower extremities and a computed tomography scan of the brain with and without contrast revealed no abnormalities. An electroencephalogram was taken and showed nothing unusual. After nonpharmacologic etiologies were ruled out, her topiramate dosage was decreased and discontinued over four days. Her mental status and myoclonus drastically improved. She was stable and discharged within 24 hours of topiramate discontinuation. Follow-up at six months revealed that her myoclonus had completely resolved. While she has experienced additional psychotic episodes, these were mild and appear to be related to her depression. Myoclonus has not returned. A patient with cerebral palsy experienced myoclonus and acute psychosis after receiving a standard dosage of topiramate for migraine prophylaxis.

Double-blind, placebo-controlled trial of risperidone plus topiramate in children with autistic disorder

Background Autism is a complex neurodevelopmental disorder that forms part of a spectrum of related disorders referred to as Autism Spectrum Disorders. The present study assessed the effects of topiramate plus risperidone in the treatment of autistic disorder. Method Forty children between the ages of 4 and 12 years with a DSM IV clinical diagnosis of autism who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to topiramate + risperidone (Group A) or placebo + risperidone (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of topiramate was titrated up to 200 mg/day depending on weight (100 mg/day for < 30 kg and 200 mg/day for > 30 kg). Patients were assessed at baseline and after 2, 4, 6 and 8 weeks after starting medication. Measure of outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Results Difference between the two protocols was significant as the group that received topiramate had a greater reduction in ABC-C subscale scores for irritability, stereotypic behavior and hyperactivity/noncompliance. Conclusion The results suggest that the combination of topiramate with risperidone may be superior to risperidone monotherapy for children with autistic disorder. However the results need to be further confirmed by a larger randomized controlled trial.

Oral Topiramate in Neonates with Hypoxic Ischemic Encephalopathy Treated with Hypothermia: A Safety Study

To investigate whether topiramate associated with mild or deep hypothermia in asphyxiated term infants is safe in relation to the short-term outcome. We report on 27 consecutive asphyxiated newborns who were treated with whole body hypothermia and 27 additional consecutive newborns with hypothermia who were co-treated with oral topiramate, once a day for 3 consecutive days, at 2 different doses. Newborns were divided in 6 groups according to the depth of hypothermia and the association with higher or lower topiramate dosage. A statistical comparison of the groups identified some differences in biochemical and hemodynamic variables, but no adverse effects attributable to topiramate were detected. There were no statistically significant differences in the groups in short-term outcomes, survival rate at discharge, or incidence of pathologic brain magnetic resonance imaging. Although the number of newborns in this study was limited, the short-term outcome and the safety data appear to support the evaluation of topiramate in clinical trials to explore its possible additive neuroprotective action.

Electronic Medical Records as a Research Tool: Evaluating Topiramate Use at a Headache Center

Electronic medical records (EMRs) are used in large healthcare centers to increase efficiency and accuracy of documentation. These databases may be utilized for clinical research or to describe clinical practices such as medication usage. We conducted a retrospective analysis of EMR data from a headache clinic to evaluate clinician prescription use and dosing patterns of topiramate. The study cohort comprised 4833 unique de-identified records, which were used to determine topiramate dose and persistence of treatment. Within the cohort, migraine was the most common headache diagnosis (n = 3753, 77.7%), followed by tension-type headache (n = 338, 7.0%) and cluster or trigeminal autonomic cephalalgias (n = 287, 5.9%). Physicians prescribed topiramate more often for subjects with migraine and idiopathic intracranial hypertension (P < .0001) than for those with other conditions, and more often for subjects with coexisting conditions including obesity, bipolar disorder, and depression. The most common maintenance dose of topiramate was 100 mg/day; however, approximately 15% of subjects received either less than 100 mg/day or more than 200 mg/day. More than a third of subjects were prescribed topiramate for more than 1 year, and subjects with a diagnosis of migraine were prescribed topiramate for a longer period of time than those without migraine. Findings from our study using EMR demonstrate that physicians use topiramate at many different doses and for many off-label indications. This analysis provided important insight into our patient populations and treatment patterns.

Antidepressant-like or anxiolytic-like actions of topiramate alone or co-administered with intra-lateral septal infusions of neuropeptide Y in male Wistar rats

We tested the effects of intra-lateral septal infusions of neuropeptide Y (NPY) combined with systemic injections of topiramate in the DRL-72 s paradigm and the elevated plus-maze test in male Wistar rats. Intra-lateral septal infusions of desipramine (5.0 μg/μl; P < 0.05) or intra-lateral septal infusions of NPY (3.0 μg/μl, P < 0.05; 3.5 μg/μl, P < 0.05) or systemic injections of topiramate (20.0 mg/kg, P < 0.05; 30.0 mg/kg, P < 0.05) or subthreshold doses of topiramate (10.0 mg/kg) combined with intra-lateral septal infusions of subthreshold doses of NPY (2.5 μg/μl; P < 0.05) induced a dose-dependent increase in reinforced lever presses and a cohesive rightward shift of the inter-response time distribution in the DRL 72 s task. In the elevated plus-maze test, intra-lateral septal infusions of NPY (3.0 μg/μl, P < 0.05; 3.5 μg/μl, P < 0.05) or midazolam (10.0 μg/μl; P < 0.05) or systemic injections of topiramate (20.0 mg/kg, P < 0.05; 30.0 mg/kg, P < 0.05) or subthreshold doses of systemic injections of topiramate (10.0 mg/kg) combined with intra-lateral septal infusions of subthreshold doses of NPY (2.5 μg/μl; P < 0.05) increased the exploration of the open arms without affecting locomotion. In conclusion, intra-septal NPY has anxiolytic effects in the EPM, and antidepressant effects in the DRL 72 s test. Similarly, systemic topiramate has anxiolytic effects in the EPM, and antidepressant effects in the DRL 72 s test. Finally, a combination of subthreshold doses of NPY and topiramate together also have anxiolytic and antidepressant effects, suggesting a synergistic effect.

Prevention of episodic migraine with topiramate: a prospective 24-week, open-label, flexible-dose clinical trial with optional 24 weeks follow-up in a community setting

Objective: To explore efficacy and safety outcomes of topiramate for episodic migraine prevention in community practice. Research design and methods: Open-label, multicenter, flexible-dose clinical trial consisting of a 4-week baseline phase, 24-week core phase and an optional 24-week follow-up phase in patients (18–80 years) with episodic migraine treated in community practices outside tertiary care centers. Main outcome measures: The primary efficacy endpoint was the change in the number of migraine days/28 days (baseline vs. the last 4 weeks of core treatment) Secondary efficacy parameters included aspects of quality of life (QoL) and subjective patient ratings. Results: A total of 360 patients entered the core phase (ITT population); 37.6% (97 patients) discontinued prematurely, mainly due to adverse events (AEs; 23.6%). Mean topiramate dosage was 90 mg/day. Migraine days decreased from 8.30/28 days to 5.65/28 days and QoL (HIT-6 and MIDAS) was improved. Efficacy, tolerability and satisfaction were rated as ‘good’ or better by 56, 61 and 63% of patients, respectively. A total of 321 of 364 patients (88.2%) reported at least one treatment emergent AE, and the most common during the core phase were paraesthesia (46.4% of 364 patients), fatigue (17.0%), nausea (15.4%), dizziness (12.9%), viral infection (12.9%), weight decrease (12.6%) and impaired concentration (10.2%). Of 227 patients completing the core phase, 199 (88%) participated in the follow-up phase. A total of 187 patients received topiramate and 38 (20.3%) of these stopped treatment prematurely due to insufficient efficacy (6.4%), AEs (4.8%) or other reasons (10.2%). Reduction in migraine days and improvements in QoL (HIT-6) were maintained or improved (MIDAS) during follow-up, and 84% rated their satisfaction with topiramate therapy as ‘good to very good’. Conclusions: This community practice study showed that long-term treatment with topiramate in the prevention of episodic migraine was effective and well-tolerated, and it was associated with clinically relevant improvements in several aspects of QoL.

Stimulating studies of visual cortical function in migraine

A variety of clinical and experimental evidence suggests that migraine involves changes in the excitability of the visual cortex. The recent study by Aurora and colleagues (1) adds to this evidence by confirming their previous finding that the response of the occipital cortex to transcranial magnetic stimulation (TMS) is different in migraine patients as compared with controls. In addition, this study shows that treatment with topiramate results in normalisation of the response to TMS in migraine patients such that it is similar to control subjects. These results are significant on multiple levels. First, they indicate that alterations in the response of the occipital cortex to TMS may be a consistent feature of migraine patients, and that this neurophysiological feature may have potential as a biomarker of the disorder. Second, they add further evidence in support of the concept that there is increased excitability in the occipital cortex of migraine patients. Finally, they show that a migraine preventive therapy reduces this excitability, suggesting that TMS paradigms may be useful for the investigation of the mechanisms by which different therapies prevent migraine. Aurora and colleagues used a method known as magnetic suppression of perceptual accuracy (MSPA) to study migraine patients before and after therapy with topiramate. A transcranial magnetic pulse delivered over the occipital cortex impairs the ability of subjects to perceive visual stimuli with a characteristic time course. The MSPA technique quantifies the accuracy with which a subject can identify a series of letters when a TMS pulse is delivered at different time intervals after the letters are presented (2). Normal subjects have a ‘U-shaped’ pattern of visual accuracy relative to the timing of the TMS pulse, i.e. they have accurate visual perception when the pulse is delivered at short (40ms) or longer (190ms) intervals after the characters are flashed, but impaired perception when the pulse is delivered at an intermediate interval (100ms). Migraine patients, by contrast, have been reported to show a reduced suppression of perceptual accuracy at the 100-ms time point, resulting in a ‘shallower’ curve of the MSPA temporal profile (2,3). Aurora and colleagues found that with increased frequency of migraine, there is even further reduction in the magnetic suppression of visual accuracy (3,4). They concluded that these findings are consistent with an increased excitability of the occipital cortex in migraine patients, possibly due to reduced cortical inhibition. In their current paper, they report that treatment with topiramate resulted in a dose-dependent restoration of the magnetic suppression of visual perception (1). The average profile of the MSPA response in patients on ‘optimal doses’ of topiramate was similar to those of controls, whereas the average MSPA profile of patients on smaller doses of topiramate was the same as that of untreated migraine patients. Overall, the extent of MSPA change did not show a significant correlation with the extent to which migraine frequency was reduced, although this correlation was present for some individual patients. One important implication of this study is that MSPA, and potentially other quantitative measures of cortical excitability based on TMS responses, could represent a ‘biomarker’ for migraine. At present, there are no laboratory, neurophysiological, or imaging studies that are consistent indicators for migraine (5). If differences in MSPA in migraine patients vs. controls can be consistently replicated in other laboratories, there is the potential for this and other approaches using TMS to become more widely used in the investigation of migraine. A key question is whether the variability of individual patient responses will be manageable enough to make more wide-spread use of this approach feasible. There may be significant variability in neurophysiological responses of migraine patients depending on when the measurements are obtained relative to the last migraine attack, or the one that is about to occur (6,7). Given this temporal

Topiramate in the Treatment of Substance-Related Disorders

To critically review the literature on topiramate in the treatment of substance-related disorders. A PubMed search of human studies published in English through January 2009 was conducted using the following search terms: topiramate and substance abuse, topiramate and substance dependence, topiramate and withdrawal, topiramate and alcohol, topiramate and nicotine, topiramate and cocaine, topiramate and opiates, and topiramate and benzodiazepines. 26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, Ecstasy, and benzodiazepines. Study design, sample size, topiramate dose and duration, and study outcomes were reviewed. There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate's superiority over oral naltrexone in alcohol dependence, while 1 trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and Ecstasy are sparse. Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate's unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance-related disorders, heterogeneity both across and within these disorders limits topiramate's broad applicability in treating substance-related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies.

A pilot study of topiramate dosages for migraine prophylaxis in an Asian population.

Topiramate is known to be efficacious in migraine prophylaxis, but its optimal dose has not been systematically studied in the Asian population. Here, we show that a fixed low dose of topiramate 25 mg/day is efficacious in migraine prophylaxis and also attest to advantages in terms of medication cost savings and more favourable side effect profile.

Comparison of Topiramate and Risperidone for the Treatment of Behavioral Disturbances of Patients With Alzheimer Disease

Behavioral disturbances are determining factors in handling patients with Alzheimer dementia. The current pharmacotherapy for behavioral symptoms associated with dementia is not satisfactory. Our goal was to compare a new anticonvulsant, topiramate, with a usually used medication, risperidone, for controlling behavioral disturbances of patients with Alzheimer dementia. Elderly patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of Alzheimer disease and significant behavioral disturbances were randomized to receive, for a period of 8 weeks, a flexible dose of either topiramate (25-50 mg/d) or risperidone (0.5-2 mg/d). Outcome measures were the Cohen-Mansfield Agitation Inventory, Neuropsychiatry Inventory parts 1 and 2, and the Clinical Global Impression. Forty-eight patients were randomized to treatment with either topiramate or risperidone, and 41 patients (21 of 25 in topiramate group and 20 of 23 in risperidone group) completed the trial. Both groups showed significant improvement in all outcome measures without important difference (Neuropsychiatry Inventory total score P < 0.531, Z = 0.62; Cohen-Mansfield Agitation Inventory P < 0.927, Z = 0.09; Clinical Global Impression, P < 0.654, Z = 0.48). There were no significant changes in the cognitive status of patients (assessed by Mini-Mental Status Examination) taking topiramate or risperidone during the trial. Treatment with a low dose of topiramate (25-50 mg/d) demonstrated a comparable efficacy with risperidone in controlling behavioral disturbances of patients with Alzheimer dementia.

Clinical experience with open-label topiramate use in epileptic children with CNS anomalies

Purpose: To investigate the effectiveness and tolerability of topiramate (TPM) in treating children with CNS anomalies and intractable epilepsy.Methods: We retrospectively searched the patient database in National Taiwan University Hospital for candidate children (younger than 18 years of age) with epilepsy and CNS anomalies from December 2002 to February 2004. The effectiveness and possible side effects of TPM were evaluated by questionnaire.Results: Twenty-two children (9 males, 13 females) aged from five months to fourteen years were enrolled in the present study. Underlying CNS anomalies were proliferation disorders (n=10), migration/organization disorders (n=10), and neurocutaneous syndromes (n=2). Types of epilepsy at TPM add-on were symptomatic partial epilepsy (n=11), infantile spasms (n=7), and Lennox-Gastaut syndrome (n=4). During the follow-up periods of six to 30 months, eight patients (36%) had more than 50% reduction of seizures and four patients (18%) were seizure-free. The average dosages of TPM ranged from 2.5 to 25 mg⁄kg⁄day. Patients with proliferation disorders or infantile spasms responded better to TPM therapy. The most common side effect was oligohidrosis (n=9, 41%).Conclusion: TPM is a safe and promising add-on anticonvulsant for epileptic children with CNS anomalies. Hypohidrosis is one of the major side effects of TPM treatment.

Topiramate-induced angle closure with acute myopia, macular striae

Topiramate is a sulfamate-substituted monosaccharide used in the treatment of seizures, and prophylaxis of migraine. A number of ocular side-effects have been described with use of topiramate, like bilateral angle closure, acute myopia and macular striae. Ultrasound biomicroscopy (UBM) clinches the diagnosis after ruling out other causes of shallow anterior chamber. Previous studies have not demonstrated internal limiting membrane folds presenting as macular striae. We report a case of topiramate-induced acute myopia with angle closure and macular striae in a young adult. This is the first report wherein striae formation after low doses of topiramate and their resolution have been documented by Optical Coherence Tomography (OCT).