Efficacy Of Topiramate Research Articles

Efficacy of Topiramate for Relapsed Epileptic Spasms in Tuberous Sclerosis: Report of Three Cases

Efficacy of Topiramate for Relapsed Epileptic Spasms in Tuberous Sclerosis: Report of Three Cases

Gender-based effect of statins on functional decline in amyotrophic lateral sclerosis

Recently an association between statins and the onset and more rapid disease course of amyotrophic lateral sclerosis (ALS) was reported, while other studies rejected such a link. The role of gender in that controversy is unclear. We evaluated the gender-specific effect of statins on the rate of functional decline in patients with ALS, based on data retrieved from the medical records of all ALS patients who participated in two previously reported clinical trials on the efficacy of topiramate and of celecoxib in ALS. The topiramate trial enrolled 294 patients, 28 (9.5%) of whom were statin users (20 males). The celecoxib trial enrolled 300 patients, 25 (8.3%) of whom were statin users (17 males). Statins had no effect on the functional decline in the celecoxib trial, but they did have a negative impact on disease course in the topiramate trial. When males and females were analyzed separately, the functional decline of females taking statins was significantly greater than that of males in both trials. Our results indicate that statins affect possibly negatively ALS progression among females but not males. They emphasize the need to consider gender in future analyses of drug effects.

Successful Treatment of Cerebellar Ataxia and Tremor in Multiple Sclerosis With Topiramate

We describe the clinical efficacy of topiramate for treatment of cerebellar dysfunction in a 33-year-old female patient with relapsing remitting multiple sclerosis. The patient presented severe ataxia and tremor precluding many activities of daily life. Topiramate was administered as a monotherapy and slowly tapered in to 150 mg daily without negative side effects. Treatment was well tolerated and led to a marked and lasting improvement of tremor as well as ataxia during an observation period of 2 years. Upon transient withdrawal of topiramate, ataxia and tremor worsened but were again improved after re-dosing of the drug. Multiple sclerosis immunotherapy was not changed in this period. In conclusion, topiramate may be a new therapeutic option to treat cerebellar tremor and ataxia in patients with multiple sclerosis.

Topiramate in the New Generation of Drugs: Efficacy in the Treatment of Alcoholic Patients

Predicated upon a neuropharmacological conceptual model, there is now solid clinical evidence to support the efficacy of topiramate for the treatment of alcohol dependence. Topiramate treatment can be initiated whilst the alcohol-dependent individual is still drinking - just when crisis intervention is most likely to be needed by a patient with or without his or her family asking the health practitioner for assistance. Because topiramate can be paired with a brief intervention, there is now the exciting possibility of treating most alcohol- dependent individuals in office-based practice or generic treatment settings. Topiramate's additional effects on other impulsedyscontrol disorders make it a particularly interesting compound for the treatment of other comorbid drug or psychiatric disorders. Additionally, future studies should explore whether topiramate can be combined with other putative therapeutic agents to increase its efficacy. One notable clinical challenge in the development of topiramate as a pharmacotherapy to treat alcohol dependence is the determination of the smallest dose that can result in efficacy, thereby achieving the optimum balance between therapeutic benefit and adverse event profile. Animal data do provide support for topiramate's general anti-drinking effects but also indicate that its mechanisms of action might rely on several complex pharmacobehavioral changes. Additional preclinical studies are needed to elucidate more clearly the basic mechanistic processes that underlie topiramate's efficacy as a treatment for alcohol dependence. Preclinical information that topiramate may have differential effects based on genetic vulnerability opens up the possibility of future methods to optimize treatment.

Topiramate intervention to prevent transformation of episodic migraine: The topiramate INTREPID study

The study sought to evaluate whether topiramate prevents development of chronic daily headache (CDH, ≥15 headache days per month) in adult subjects with high-frequency episodic migraine (HFEM, 9-14 migraine headache days/month). A secondary objective was to assess the efficacy of topiramate as preventive migraine treatment in this population. This was a multicenter, randomized, double-blind, placebo-controlled study comparing topiramate 100 mg/day and placebo for 26 weeks. The primary efficacy variable was new-onset CDH at month 6. Secondary efficacy measures included migraine and headache days. Adverse events (AEs) were evaluated. A total of 159 topiramate subjects and 171 placebo subjects were efficacy-evaluable. At month 6, 1.4% of topiramate subjects versus 2.3% of placebo subjects had CDH (p = .589). Compared with placebo, topiramate treatment was associated with statistically significant reductions in mean number of migraine days (6.6 vs. 5.3/28 days; p = .001) and headache days (6.6 vs 5.3/28 days; p = .001). Most commonly reported AEs in the topiramate versus placebo group included paresthesia (32.4% vs. 7.0%), fatigue (14.8% vs. 8.6%), dizziness (11.4% vs. 7.6%) and nausea (10.8% vs. 9.2%). Topiramate 100 mg/day did not prevent the development of CDH at six months in subjects with HFEM. Topiramate was effective in reducing headache days and migraine headache days and generally well tolerated.

An Open-Label Trial of Topiramate in the Treatment of Skin Picking in Pervasive Developmental Disorder Not Otherwise Specified

An Open-Label Trial of Topiramate in the Treatment of Skin Picking in Pervasive Developmental Disorder Not Otherwise Specified

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.

Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: A double-blind, placebo-controlled trial

BackgroundOlanzapine associated weight gain (WG) is a major concern in patients with schizophrenia. The purpose of this study was to assess the efficacy of topiramate to prevent olanzapine induced WG in these cases. We also studied various metabolic parameters. MethodsIn this 12-week, double-blind, parallel group study, seventy-two drug-naïve, first-episode schizophrenia patients were randomized to receive olanzapine+placebo (olanzapine group) or olanzapine+topiramate (100mg/day) (topiramate group). Weight, body mass index, fasting glucose, insulin, insulin resistance (IR), leptin, lipids and blood pressure were assessed at baseline and at 12weeks. The patients were clinically evaluated using Positive and Negative Syndrome Scale (PANSS) and were monitored for adverse effects. ResultsTopiramate resulted in a weight loss of 1.27±2.28kg (p<0.01), decrease in leptin (p<0.001), glucose, cholesterol, triglyceride levels and systolic and diastolic blood pressure. In the olanzapine group, there was a significant WG, hyperglycemia, hyperinsulinemia, increased IR, hyperleptinemia, hypercholesterolemia and hypertriglyceridemia (p<0.001).There was a greater clinical improvement (PANSS scores) (p<0.001) in the topiramate group. The adverse effects were well tolerated. ConclusionsTopiramate could prevent olanzapine induced weight gain and adverse metabolic effects. It also results in a greater clinical improvement when used with olanzapine in schizophrenia.

Topiramate‐Induced Intractable Cough During Migraine Prophylaxis

Topiramate is a highly effective drug in migraine prophylaxis and is considered a first-line treatment. The evidence for the efficacy of topiramate is based upon the results of several large, randomized, double-blind, placebo-controlled trials. Adverse events (AEs) are common and require discontinuation of the treatment in about 20-25% of patients, but they are rarely severe. There are reviews regarding topiramate-related AEs representing a large number of patients treated in controlled trials. The most common AEs are weight loss, dizziness, somnolence, abnormal thinking, fatigue, ataxia, confusion, paresthesias, impaired concentration, nervousness, amnesia, and language difficulties. The development of cough has never been reported as an AE during topiramate prophylaxis for migraine. We present 3 cases in which the prophylactic treatment for migraine with topiramate was discontinued due to the onset of primary intractable coughing.

Topiramate in Treatment of Tourette Syndrome

To describe the efficacy and safety of topiramate in the treatment of Tourette syndrome (TS). Charts of subjects whose conditions were diagnosed as tic disorders seen at our clinic from 2003 to 2007 were retrospectively reviewed. Patients who met diagnostic criteria for TS and were started on topiramate at our clinic with at least 1 follow-up visit after beginning topiramate were included. The efficacy of topiramate on a subjective scale, the global impression of response (0 = no response/worse, 1 = mild improvement, 2 = moderate improvement, 3 = marked improvement), and adverse effects were recorded for analysis. Of 453 subjects, 367 met diagnostic criteria for TS and 41 (11.1%; 34 males) were treated with topiramate for tics for 9.43 +/- 7.03 months (range, 1-27 months). Mean age at onset of tics was 6.93 +/- 2.78 years (range, 2-14 years) and at start of topiramate treatment was 14.83 +/- 5.63 years (range, 9-27 years). The average efficacy on tics was 2.15 +/- 1.11, and 75.6% (n = 31) of subjects had moderate to marked improvement and adverse effects included cognitive/language problems (24.4%, n = 10) and aggression or mood swings (9.8%, n = 4). This retrospective chart review suggests that topiramate can be used for tics in TS with at least moderate efficacy and typical adverse effects. Randomized controlled trials are needed.

Efficacy of Topiramate in Childhood Epilepsies

Efficacy of Topiramate in Childhood Epilepsies

PW01-237 - Low-dosage topiramate in alcohol dependence: a randomized, double-blind, placebo-controlled trial

IntroductionTopiramate (up to 300 mg per day) is more efficacious than placebo as an adjunct to standardised medication compliance management in treatment of alcohol dependence. However, adverse events can limit its use in different clinical situation. In this randomised, double-blind, placebo controlled trial we aimed to investigate the efficacy of low-dosage topiramate on alcohol drinking indices. Craving and psychiatric symptoms improvements were the secondary endpoints.MethodsForty alcohol dependent subjects where detoxified and subsequently randomised into two groups, respectively receiving topiramate (100mg/die) or Placebo. The level of craving for alcohol was evaluated by a 10-cm Visual Analogue Scale (VAS) and the Italian -version of the Obsessive and Compulsive Drinking Scale (OCDS). Psychiatric symptomatology was evaluated by the Symptom Check List 90 Revised (SCL-90 R).ResultsThe improvement of alcohol drinking indices and craving scores was higher in the topiramate group than placebo. The survival function showed that patients treated with topiramate remained abstinent from any alcohol amount for a longer time with respect to placebo (Z= -2.197; P&lt; 0.05). The SCL-90-R general index of “Positive Symptom Total” significantly reduced in the topiramate group (F= 3.41, p&lt; 0.05). The number of patients dropped-out from the study for adverse events was not different between groups.DiscussionTo our knowledge, this is the first randomised, parallel group trial to evaluate the efficacy of topiramate at low dosage for alcohol dependence. The use of topiramate at low dosage could increase the number of subjects in treatment, given the reduced possibility of adverse events.

Clinical Assessment of Topiramate Therapy in Patients With Migrainous Vertigo

To assess the efficacy of topiramate in reducing both the frequency and the severity of vertigo and headache attacks in patients with migrainous vertigo and to compare 50 and 100 mg/day doses of the drug. Thirty patients diagnosed as definite migrainous vertigo were recruited in the study. Vertigo and headache frequency was determined as the monthly number of attacks whereas severity was determined by visual analog scales measured in millimeters from 0 to 100. Patients were randomized to either 50 or 100 mg/day topiramate for 6 months. Vertigo and headache frequency and severity were evaluated at the end of the study period. Number of mothly vertigo attacks decreased significantly in the overall group after treatment (median from 5.5 to 1; P < .01). The same was true for monthly headache attacks (median from 4 to 1; P < .01). A statically significant improvement in vertigo severity was noted (median from 80 to 20 mm; P < .01). Headache severity showed significant improvement as well (median from 60 to 30 mm; P < .01). No statistically significant difference between high- and low-dose groups was present regarding efficacy (P > .05). Four patients in the high-dose group discontinued treatment at the end of the first month because of adverse effects. In the overall group, topiramate was found to be effective in reducing the frequency and the severity of vertigo and headache attacks. Both doses of the drug were equally efficacious. The 50 mg/day dose seems to be appropriate as higher adverse effects were noted when 100 mg/day was used.

PW01-248 - Topiramate as an adjunct in alcohol detoxification process

BackgroundAnticonvulsants have been used for the treatment of affective and anxiety symptoms secondary to alcohol abuse as well as craving. In this open label study we investigated efficacy of topiramate as an adjunct in alcohol detoxification; end targets were anxiety, depression and in obsessive-compulsive drinking.MethodsTwo groups matched for age, alcohol consumption and demographic characteristics, were treated either with psychotherapy (n=43) or psychotherapy and topiramate (n=43). Subjects were assessed twice (baseline and after a 4-6 week detoxification period) by the Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, and the Obsessive Compulsive Drinking Scale. T-tests were used for comparisons between groups.ResultsFollowing detoxification, psychopathology significantly subsided in both groups; however, improvement was more robust in the topiramate group (table 1). HDRS admissionHDRS dischargeHARS admissionHARS dischargeOCDS admissionOCDS dischargeTopiramate group39.2 ± 4.26.7 ± 4.3*33.9 ± 6.45.5 ± 6.5*42.3 ± 3.28.2 ± 3.3*Control group38.7 ± 5.39.8 ± 7.4*32.3 ± 10.69.5 ± 6.5*41.5 ± 2.615.2 ± 2.4*[Table 1]DiscussionTopiramate in conjunction with a short-term psychotherapeutic approach may help the alcohol detoxification process by minimizing craving and subjective physical discomfort. Moderate to severe anxiety and depressive symptoms with concomitant poor functioning were present in all subjects before treatment. Following 4-6 weeks of alcohol detoxification, a considerable improvement in terms of anxiety and depressive symptoms was observed in both groups. However, in our sample, a significantly more robust decrease was recorded in the topiramate augmentation group. Consequently, topiramate can be of potential help in this population and can be used as an alternative among other treatment options.

Topiramate in prevention of cluster headache in the Taiwanese

Topiramate could potentially effective as prophylaxis for cluster headache, but the experience remains limited in Asians. We performed an open-label clinical study to evaluate the efficacy of topiramate in the tolerable dosage to prevent cluster headache. We studied patients who fulfilled the criteria of episodic or chronic cluster headaches (International Classification of Headache Disorders second edition) prospectively. Headache severity was assessed using a verbal rating scale (excruciating, severe, moderate, mild, and no headache). Treatment was started with a topiramate dose of 50 mg twice daily and was increased by 50-100 mg a day every 3 to 7 days as tolerated to a maximal daily dosage of 400 mg. Of the 12 patients with episodic cluster headache, nine patients had remission of headache at a mean daily dosage of 273 mg (range 100-400 mg), and the patient with chronic cluster headache had remission at a daily dosage of 400 mg. The adverse effects included: paresthesia (84%), slow speech (54%), and dizziness (46%), but were tolerated by most patients. Two patients discontinued topiramate due to adverse events and one due to lack of efficacy. This open-label study suggests that topiramate is effective in the treatment of cluster headache in Taiwanese patients.

Topiramate efficacy in treatment of children with West syndrome

The aim of our study was to assess prospectively the efficacy and tolerability of topiramate in treatment of children with West syndrome. Furthermore, we analyzed the effectiveness of topiramate in relation to etiology. Nineteen patients with West syndrome, aged 4 to 12 months, who were treated at the Pediatric Clinic, University Hospital of Split, Croatia between 2003-2005 were evaluated. The most common etiology was hypoxic-ischemic encepalopathy, which was the cause of seizures in 10 patients, followed by developmental cortical anomalies in 3 cases. Tuberous sclerosis was found in 2 patients and a porencephalic cyst was established in 1 patient. One patient was diagnosed with Down’s syndrome and another with a metabolic disease. For 1 patient the etiology of West syndrome remained unknown. Ten patients out of 19 improved significantly with reduction of seizure frequency of 50-75%. In 5 patients the reduction of seizure frequency was over 75% and in 4 it was 25-50%. Topiramate is effective in the treatment of children younger than 12 months with West syndrome, especially in those with hypoxic-ischemic brain injury causing seizures.

Effects of topiramate or naltrexone on tobacco use among male alcohol-dependent outpatients

Background A high smoking prevalence has been registered among alcoholics. It has been pointed out that alcoholic smokers may have a more severe course and greater severity of alcoholism. This study aims at comparing smoking and non-smoking alcoholics in terms of treatment outcomes and verifying the efficacy of topiramate and naltrexone to decrease the use of cigarettes among alcoholic smokers. Methods The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of São Paulo, Brazil. The sample comprised 155 male alcohol-dependent outpatients (52 non-smokers and 103 smokers), 18–60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period, the patients randomly received placebo, naltrexone (50 mg/day) or topiramate (up to 300 mg/day). Only the alcoholic smokers who adhered to the treatment were evaluated with reference to the smoking reduction. Results Cox regression analysis revealed that the smoking status among alcoholics increased the odds of relapse into drinking by 65%, independently of the medications prescribed, using the intention-to-treat method. Topiramate showed effectiveness to reduce the number of cigarettes smoked when compared to placebo among adherent patients (mean difference = 7.91, p < 0.01). There were no significant differences between the naltrexone group and the placebo group. Conclusions The results of this study confirm that the treatment is more challenging for smoking alcoholics than for non-smoking ones and support the efficacy of topiramate in the smoking reduction among male alcoholic smokers who adhered to the treatment.

The Abnormal Recovery Cycle of Somatosensory Evoked Potential Components in Children with Migraine can be Reversed by Topiramate

The aim of this study was to compare the recovery cycle of somatosensory evoked potentials (SEPs) in children with migraine without aura before and after treatment with topiramate. Eleven migraine children were studied before and after a 3-month treatment with topiramate at the average dose of 1.3 mg/kg/day. We calculated the SEP latency and amplitude modifications after paired electrical stimuli at 5, 20 and 40 ms interstimulus intervals, comparing them with a single stimulus condition assumed as baseline. In nine patients, who had a significant reduction in headache frequency after treatment, the recovery cycles of the P24 (P = 0.03) and N30 (P < 0.005) potentials were longer after than before topiramate treatment. In two migraineurs who did not show any improvement, the recovery cycles of the cortical SEP components were even shorter after treatment. Our results suggest that topiramate efficacy in paediatric migraine prophylaxis is probably related to restored cortical excitability.

Review of Topiramate: An Antiepileptic for the Treatment of Alcohol Dependence

Despite the availability of currently approved medications and various psychosocial therapies, alcohol abuse and dependence are increasingly prevalent in the United States, and carry a significant socioeconomic burden. Recently, the novel anti-epileptic topiramate has shown great promise as a new treatment for this disorder. The objective of this review is to discuss the limitations of the currently available options for treating alcohol dependence, to review the results of clinical trials assessing the efficacy of topiramate in treating alcohol dependence, and to describe the pharmacological characteristics and mechanisms of action of topiramate as related to this indication. We systematically reviewed Medline, EMBASE, Cochran Reviews and PsycINFO search terms included combinations of the terms "pharmacotherapy" "topiramate", "alcoholism" and "alcohol dependence." Searches were last updated 24 October 2008. Currently approved treatments include disulfiram, naltrexone tablets and injection, and acamprosate. Of these, naltrexone has shown the most benefit, however the effect size is small and may reach its most promising potential when combined with medical management. Alternatively, through multiple mechanisms of action, topiramate in clinical trials has demonstrated safety and efficacy in decreasing both craving and withdrawal symptoms and increasing quality of life measures among alcohol-dependent individuals. The findings of this review suggest that topiramate is a promising new option for the treatment of alcohol dependence, and may offer substantial benefits over currently approved medications. While the manufacturer will not pursue approval of an indication for the treatment of alcohol dependence, the drug will soon be available generically, making it more affordable for a greater proportion of the public.

Effects of Topiramate on Smoking in Patients with Schizoaffective Disorder, Bipolar Type: Response to Khazaal and Zullino.

To the Editors: We recently published a secondary analysis of expired breath carbon monoxide (CO) levels (a measure of smoking exposure) in patients with schizoaffective disorder, bipolar subtype, participating in a clinical trial of topiramate for treating psychiatric symptoms (1). Our analysis found that CO levels remained generally unchanged for participants on topiramate and placebo during the course of the trial. In our discussion, we noted that one limitation of the study was the assessment of smoking by CO level only. Khazaal and Zullino (this issue) further discuss concerns about the suitability of CO as a measure of changes in smoking. Khazaal and Zullino suggest that CO may be a poor indicator of smoking reduction because decreases may be attenuated through increased intensity with which those cigarettes are smoked (i.e. compensation). Because it is highly dependent on the recency of smoking, we agree that CO is a more labile measure of smoking exposure than other biochemical measures (e.g., cotinine). However, a significant change in smoking consumption (cigarettes per day, CPD) should still result in a noticeable change in CO levels, even with some change in the intensity of smoking. Studies of the efficacy of transdermal nicotine patch (2) and bupropion (3) for smoking cessation in smokers with schizophrenia have shown parallel decreases in CO level consistent with decreases in CPD. It is possible that topiramate was associated with small changes in CPD that were masked through smoking compensation, our small sample size, or the infrequent CO assessments. However, small changes in smoking consumption that do not result in decreases in CO levels may not be clinically significant in terms of beneficial health outcomes for patients. In other words, it is overall smoke exposure, as indicated by CO, that is the more valid marker of health risk, rather than cigarettes per day, regardless of how they may be smoked. In order to clarify the usefulness of topiramate for smoking cessation with smokers with psychiatric disorders, further research is needed. Clinical trials comparing topiramate to placebo should be conducted in larger samples of smokers with psychiatric disorders using multiple assessments of smoking at frequent time points. Patient-reported changes in smoking consumption (CPD) should be confirmed using CO and cotinine levels. Questions about changes in smoking intensity with topiramate can be assessed through smoking topography techniques. One study (4) has examined changes in smoking topography for topiramate (75mg/day) compared to placebo in nonpsychiatric smokers. Topiramate resulted in decreased puff volume and enhanced reward from smoking, but also no differences in total puffs per cigarette and increased withdrawal during smoking abstinence. Topiramate-induced changes in smoking topography have not been examined for smokers with psychiatric disorders. Finally, the main purpose of the clinical trial was to examine the efficacy of topiramate for mood and psychotic symptoms in patients with schizoaffective disorder. Patients were not necessarily motivated to quit smoking and were not provided with smoking cessation counseling. Future studies should examine the efficacy of topiramate in conjunction to behavioral smoking cessation counseling in patients with current motivation to quit smoking. While our data does not suggest spontaneous decreases in smoking or CO levels for smokers with schizoaffective disorder, future studies that address the limitations of our analysis would provide a clearer picture of the clinical usefulness of topiramate for smoking cessation in this population.