topiramate and Body-Weight

This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect.. Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction.. For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work.. Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo.  DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity.. This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension.. In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Bias; Blood Pressure; Body Weight; Bupropion; Diet, Reducing; Drug Combinations; Female; Fructose; Humans; Hypertension; Lactones; Male; Middle Aged; Naltrexone; Orlistat; Phentermine; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Time; Topiramate

The study objective was to examine the association between phentermine/topiramate therapy and weight loss and adverse events in adults with overweight or obesity by meta-analysis and systematic review.. Medical Subject Headings and free-text terms were selected to search for eligible trials in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase up to April 18, 2020. The quality of randomized controlled trials was evaluated by the Cochrane risk-of-bias tool. Meta-analysis was performed using random-effect models.. Phentermine/topiramate therapy resulted in an average weight loss of 7.73 kg (95% CI: 6.60-8.85) in general compared with placebo. The weight loss was related to the dose of phentermine/topiramate. Compared with placebo, the average weight loss was 3.55 kg (95% CI: 2.22-4.88) for 3.75/23 mg, 7.27 kg (95% CI: 6.40-8.13) for 7.5/46 mg, and 8.25 kg (95% CI: 6.92-9.79) for 15/92 mg. For phentermine/topiramate participants in different weight-loss subgroups, the weight loss of participants with ≥5%, ≥10%, and ≥15% baseline weight loss was 3.18 (95% CI: 2.75-3.67), 5.32 (95% CI: 4.53-6.25), and 5.65 (95% CI: 3.55-9.01), respectively. Compared with placebo, the adverse events associated with the treatment mainly included dysgeusia (odds ratio [OR] = 8.86, 95% CI: 5.65-13.89), paresthesia (OR = 8.51, 95% CI: 6.20-11.67), dry mouth (OR = 6.71, 95% CI: 5.03-8.94), disturbance in attention (OR = 4.48, 95% CI: 2.39-8.41), irritability (OR = 4.10, 95% CI: 2.29-7.33), hypoesthesia (OR = 3.81, 95% CI: 1.32-11.00), constipation (OR = 2.43, 95% CI: 2.02-2.93), and dizziness (OR = 2.26, 95% CI: 1.72-2.98). Phentermine/topiramate also reduced waist circumference, blood pressure, blood sugar levels, and lipid levels.. Phentermine/topiramate has considerable benefit in reducing body weight, and the efficacy was closely related to the dosage. However, it increased the risk of nervous system-related adverse events.

Topics: Adult; Blood Pressure; Body Weight; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Obesity; Overweight; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; Weight Loss

To systematically determine the effectiveness of Topiramate to counteract atypical antipsychotic-induced body weight gain and metabolic adversities in patients with psychiatric disorders.. A literature search using MEDLINE, EMBASE, PsycINFO, The Cochrane Library, CNKI, CBM and WanFang Data for randomized, open and double-blind, placebo-controlled trials of Topiramate targeting atypical antipsychotic-induced weight gain was performed.Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies.Then meta-analysis was performed using RevMan 5.2 software.. A total of 10 RCTs was included, consisting of 453 subjects. The results of meta-analysis showed that: compared with placebo, Topiramate was moderate effective in reducing antipsychotics-related weight gain (WMD=-1.82 kg (95%CI: -2.65--0.99), P<0.000 1), BMI increase (WMD=-1.31 kg/m(2) (95%CI: -1.69--0.93), P<0.000 01) and fasting glucose increase (SMD=-1.15 (95%CI: -1.50--0.79), P<0.000 01); but can not regulate the lipid metabolic disorders (Cholesterol: SMD=-0.23 (95%CI: -0.81-0.35), P=0.44); Triglycerides: SMD=-0.28 (95%CI: -0.75-0.19), P=0.24; HDL: SMD= 0.01 (95%CI: -0.52-0.53), P=0.98); LDL: SMD=-0.39 (95%CI: -0.89-0.11), P=0.13). Meanwhile, when compared with placebo, Positive and Negative Syndrome Scale (PANSS) in patients with schizophrenia did not show obviously clinical improvement in concomitant Topiramate group.. Topiramate can prevent and/or treat atypical antipsychotic induced weight gain and glucose disorder, but current evidence does not support the effect of Topiramate in lipid metabolic regulation and the clinical symptoms improvement assessed by PANSS.

Topics: Antipsychotic Agents; Body Weight; Double-Blind Method; Fructose; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Topiramate; Weight Gain

To conduct a systematic review with meta-analysis to determine the efficacy and safety of topiramate as monotherapy for weight reduction in patients with type 2 diabetes mellitus.. We searched MEDLINE, Embase, and International Pharmaceutical Abstracts from inception to June 2015. We included randomized controlled trials that evaluated topiramate monotherapy versus control agents or placebo for weight loss in obese type 2 diabetes patients.. Of the 284 studies identified, 5 studies fulfilled the inclusion criteria. Topiramate decreased weight by a mean difference of 3.4kg (95% CI, -3.79 to -3.04) compared to placebo. Mean HbA1c reduction of -0.4% (95% CI, -0.58 to -0.32) and mean BMI reduction of -1.43kg/m(2) (95% CI, -1.83 to -1.03) were both significantly observed with topiramate (p<0.00001). Serious and total adverse events occurred more commonly among topiramate users, with a risk ratio for serious adverse events of 1.69 (95% CI, 1.00-2.87). All but one study had high risk of bias.. Topiramate monotherapy reduced weight in obese type 2 diabetes patients, but increased adverse events including serious adverse events. Given these safety concerns and the absence of data on clinically meaningful efficacy endpoints, clinicians should generally avoid use of topiramate alone for this indication.

Topics: Body Weight; Diabetes Mellitus, Type 2; Fructose; Humans; Neuroprotective Agents; Topiramate; Weight Loss

To meta-analyze the efficacy and tolerability of topiramate-antipsychotic cotreatment in schizophrenia.. PubMed/MEDLINE database were searched until September 5, 2015, using the keywords topiramate AND antipsych* OR neurolept* OR specific antipsychotic names.. Randomized controlled trials (RCTs) of topiramate-antipsychotic cotreatment versus placebo and ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders were included.. Two evaluators extracted data. Standardized mean difference (SMD), weighted mean difference (WMD), and risk ratio (RR) ± 95% CIs were calculated.. In 8 RCTs, lasting a mean ± SD of 13.6 ± 4.9 weeks, 439 patients were randomized to topiramate (100-400 mg/d) versus placebo (trials = 7) or ongoing antipsychotic treatment (trial = 1). Topiramate outperformed the comparator regarding total psychopathology (trials = 6, n = 269, SMD = -0.57 [95% CI, -1.01 to -0.14], P = .01), positive symptoms (trials = 4, n = 190, SMD = -0.56 [95% CI, -1.0 to -0.11], P = .01), negative symptoms (trials = 4, n = 190, SMD = -0.62 [95% CI, -1.13 to -0.10], P = .02) general psychopathology (trials = 3, n = 179, SMD = -0.69 [95% CI, -1.27 to -0.11], P = .02), body weight (trials = 7, n = 327, WMD = -3.14 kg [95% CI, -5.55 to -0.73], P = .01), and body mass index (BMI) (trials = 4, n = 198, WMD = -1.80 [95% CI, -2.77 to -0.84], P = .0003). Topiramate's efficacy for total psychopathology and weight reduction effects were not mediated/moderated by trial duration, topiramate dose, sex, age, inpatient status, baseline Positive and Negative Syndrome Scale, or baseline BMI. Conversely, clozapine-topiramate cotreatment moderated greater efficacy, but less weight loss, compared to topiramate-nonclozapine antipsychotic combinations. All-cause discontinuation was similar between topiramate and control groups (trials = 7, RR = 1.24 [95% CI, 0.76 to 2.02], P = .39). Topiramate trended only toward more paresthesia than placebo (trials = 4, RR = 2.03 [95 % CI, 0.99 to 4.18], P = .05).. Topiramate-antipsychotic cotreatment significantly reduced total, positive, negative, and general psychopathology and weight/BMI in patients with schizophrenia spectrum disorder while being well tolerated. However, larger studies are needed to confirm and extend these findings.

Topics: Antipsychotic Agents; Body Weight; Drug Therapy, Combination; Fructose; Humans; Odds Ratio; Psychiatric Status Rating Scales; Psychometrics; Psychopathology; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Topiramate; Treatment Outcome

For the first time, patients who are obese are able to benefit from 5 different FDA approved pharmacologic agents for chronic weight management. Although weight loss from all of these medications was limited to 5% to 10% of total body weight loss in the Phase III clinical trials, patients are capable of losing more weight when a cumulative approach of diet, exercise, and multiple medications are used. A pilot study of adding phentermine to lorcaserin yielded double the weight loss than lorcaserin alone. A higher percentage of total body weight is lost with use of combination phentermine/topiramate compared to orlistat, lorcaserin, and bupropion/naltrexone but there are more contraindications to its use and potential cardiovascular adverse effects due to adrenergic agonism. Lorcaserin and bupropion/naltrexone yielded similar weight loss but carry different adverse effect profiles and interactions with other psychiatric medications may preclude use of one over the other. When choosing a medication for obesity, several factors need to be considered, such as comorbidities, medication interactions, and risk of potential adverse effects.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Body Weight; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Female; Fructose; Humans; Obesity; Phentermine; Pilot Projects; Topiramate; Weight Loss

Binge eating disorder (BED), a formal eating disorder diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), is characterized by recurrent binge eating, marked distress about binge eating, and the absence of extreme weight compensatory behaviors. BED is more prevalent than other eating disorders, with broader distribution across age, sex and ethnic/racial groups, and is associated strongly with obesity and heightened risk for psychiatric/medical comorbidities.. This article provides an overview of pharmacotherapy for BED with a focus on Phase III randomized controlled trials (RCTs). The search with minimal methodological inclusion requirements yielded 22 RCTs investigating several different medication classes; most were pharmacotherapy-only trials with 8 trials testing combination approaches with psychological-behavioral methods.. The evidence base regarding pharmacotherapy for BED remains limited, although this year the FDA approved the first medication (i.e., lisdexamfetamine dimesylate; LDX) specifically for moderate-to-severe BED. Data from RCTs suggest certain medications are superior to placebos for reducing binge eating over the short term; almost no data exist regarding longer-term effects of pharmacotherapy for BED. Except for topiramate, which significantly reduces both binge eating and weight, tested medications yield minimal weight loss and LDX is not indicated for weight loss. Psychological-behavioral and combination approaches with certain medications yield superior outcomes to pharmacotherapy-only acutely and over longer-term follow-up.

Topics: Anti-Obesity Agents; Anticonvulsants; Antidepressive Agents; Binge-Eating Disorder; Body Weight; Clinical Trials, Phase III as Topic; Fructose; Obesity; Randomized Controlled Trials as Topic; Topiramate; Weight Loss

Obesity may lead to the development of multiple chronic disease states, including hypertension, dyslipidemia, and type 2 diabetes mellitus. Over a half billion adults worldwide are affected by obesity, and more than two-thirds of adults are either obese or overweight in the United States. Diet and exercise have been the mainstays of treatment in this population; however, once failed, noninvasive, long-term effective treatment modality is lacking, and medications may potentially fill the void. Lorcaserin and phentermine/topiramate were approved by the FDA in June 2012 and July 2012, respectively, as adjuncts to diet and exercise for chronic weight management of obese (body mass index [BMI] ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) individuals with comorbidities.. To review the phase 3 trials of lorcaserin and phentermine/topiramate and provide managed care considerations that may be taken into account as a result.. A MEDLINE review was performed for articles published and available through September 17, 2012, using keywords "lorcaserin" or "phentermine/topiramate" with an emphasis on phase 3 trials. The literature search was limited to randomized controlled trials in humans published in the English language. Additional information on lorcaserin from its FDA review was obtained from the FDA website.. 5 pivotal phase 3 trials were identified: 3 for lorcaserin and 2 for phentermine/topiramate. Both agents demonstrated a statistically significant higher proportion of individuals who lost ≥ 5% of body weight, as well as higher mean weight loss when compared with placebo. Safety concerns for lorcaserin include cardiac valvulopathy and increased risk of psychiatric, cognitive, and serotonergic adverse effects. Teratogenicity and increased heart rate are major safety concerns regarding phentermine/topiramate.. Health care decision makers have many factors to consider when developing strategies to fight obesity. Despite a great need for new therapies to treat obesity, medications used for weight loss have significant side-effect profiles and contraindications that may limit therapy. An appropriate utilization management strategy is needed.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Body Weight; Clinical Trials, Phase III as Topic; Female; Fructose; Humans; Male; Obesity; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Weight Loss

With an ever-growing population of obese people as well as comorbidities associated with obesity, finding effective weight loss strategies is more imperative than ever. One of the challenges in curbing the obesity crisis is designing successful strategies for long-term weight loss and weight-loss maintenance. Currently, weight-loss strategies include promotion of therapeutic lifestyle changes (diet and exercise), pharmacological therapy, and bariatric surgery. This review focuses on several pharmacological targets that activate central nervous system pathways that normally limit food intake and body weight. Though it is likely that no single therapy will prove effective for everyone, this review considers several recent pre-clinical targets, and several compounds that have been in human clinical trials.

Topics: Agouti-Related Protein; alpha-MSH; AMP-Activated Protein Kinases; Anti-Obesity Agents; Appetite Regulation; Body Weight; Cannabinoid Receptor Modulators; Central Nervous System; Ciliary Neurotrophic Factor; Energy Metabolism; Fructose; Humans; Hypothalamic Hormones; Hypothalamus; Intercellular Signaling Peptides and Proteins; Melanins; Multienzyme Complexes; Nerve Tissue Proteins; Neuropeptide Y; Obesity; Pituitary Hormones; Protein Serine-Threonine Kinases; Proteins; Receptors, Melanocortin; Signal Transduction; Topiramate

To review the use of topiramate for the treatment of binge-eating disorder (BED) associated with obesity.. MEDLINE (1966-July 2006) and the Cochrane Database (2006, issue 3) were used to conduct an English-language literature search. Key search terms included eating disorder, binge-eating, and topiramate. Bibliographies of identified articles were examined for additional references.. BED is characterized by excessive food intake with lack of control during eating episodes, but without subsequent compensatory weight loss mechanisms, and is often associated with obesity and psychiatric disorders. Evidence suggests that topiramate may have mood-stabilizing properties and cause decreased appetite and weight. One case series, 1 case report, 2 open-label studies, and 1 placebo-controlled trial have described the use of topiramate for BED associated with obesity. Doses ranging from 50 to 1400 mg/day were stated to be effective in these reports. Adverse reactions included paresthesias, cognitive impairment, somnolence, and gastrointestinal distress. Although these adverse effects were transient, they may interfere with patients' tolerability of topiramate therapy.. Albeit limited, evidence suggests that topiramate may be a viable short- and long-term treatment alternative for BED associated with obesity for patients with limited options. Further controlled trials are necessary to establish topiramate's place in therapy, optimal dosing, and length of treatment for this eating disorder.

Topics: Anti-Obesity Agents; Body Weight; Bulimia Nervosa; Fructose; Humans; Obesity; Topiramate

Lithium alone or in combination with other psychotherapeutic drugs has long been the gold standard of management for bipolar disorder (BD). Recognition of its limitations in the acute and chronic management of BD has led to the development of alternative therapies. One such approach involves the use of antiepileptic drugs (AEDs). The AED topiramate is currently being studied in the efficacy and management of BD. Topiramate has mechanisms in common with other AEDs, including sodium channel-blocking activity and enhancement of cerebral GABA concentrations. Open-label trials have evaluated topiramate at mean daily doses of 100 to 300 mg in various BD subtypes, including acute mania, depression, rapid-cycling, mixed states, and BD refractory to other medications. Results from these trials suggest topiramate may be efficacious in BD subtypes, particularly in rapid-cycling patients and those refractory to conventional treatment. Its side effect profile appears benign when used as monotherapy or in combination with other mood stabilizers. Placebo-controlled, double-blind studies are warranted to evaluate topiramate further in BD.

Topics: Affect; Anticonvulsants; Bipolar Disorder; Body Weight; Clinical Trials as Topic; Drug Resistance; Drug Therapy, Combination; Drug Tolerance; Fructose; Humans; Topiramate; Treatment Outcome

The effects of topiramate on food intake and body composition were investigated in rats fed a high-fat diet and compared with rats that were pair fed or treated with D-fenfluramine. Topiramate (40 mg. kg. d for 80 d) reduced body-weight gain in a manner similar to that of pair-fed rats and D-fenfluramine-treated rats. The reduction in body fat accounted for all the weight reduction after topiramate treatment but not after pair feeding or D-fenfluramine treatment. Topiramate reduced food intake acutely and increased metabolic rate. There were also significant reductions in leptin, insulin, and corticosterone. In the hypothalamus, topiramate increased mRNA for neuropeptide Y, reduced mRNA for neuropeptide-Y Y1 and Y5 receptors, corticotropin-releasing hormone (CRH), and type II glucocorticoid receptors but had no effect on mRNA levels for the short or long form of the leptin receptor. In peripheral tissues, topiramate reduced leptin mRNA in adipose tissue, had no effect on uncoupling protein 1 mRNA in brown adipose tissue but had tissue-selective effects on uncoupling proteins 2 and 3 mRNA levels in white and brown adipose tissues and muscle. In conclusion, topiramate is an effective inhibitor of weight gain in rats on a high-fat diet, but the mechanism through which the change in energy balance is achieved is unclear.

Topics: Animals; Body Composition; Body Weight; Carrier Proteins; Diet; Dietary Fats; Eating; Energy Metabolism; Fructose; Hormones; Ion Channels; Male; Membrane Proteins; Membrane Transport Proteins; Mitochondrial Proteins; Models, Animal; Neuropeptides; Neuroprotective Agents; Proteins; Rats; RNA, Messenger; Time Factors; Topiramate; Uncoupling Protein 1; Uncoupling Protein 2; Uncoupling Protein 3

Topiramate (TOP) blocks glutamate receptors and facilitates GABA (γ-aminobutyric acid) neurotransmission, effects that may facilitate smoking cessation. We compared the effects of behavioral counseling combined with (a) TOP, (b) TOP/nicotine patch (TOP/NIC), or (c) placebo (PLC) for smoking cessation.. We conducted a 10-week randomized trial in which subjects and research personnel were blinded to TOP versus PLC but not to the TOP/NIC patch condition. In groups receiving TOP, the medication dosage was titrated gradually up to 200 mg/day. The smoking quit date (QD) was scheduled after 2 weeks of medication treatment. NIC (21 mg) was started on the QD in subjects randomized to the TOP/NIC condition. The main outcome measure was the end-of-treatment, 4-week continuous abstinence rate (CAR; biochemically confirmed).. Fifty-seven subjects were randomized to treatment. The 4-week CAR was 1 of 19 (5%) in the PLC group, 5 of 19 (26%) in the TOP group, and 7 of 19 (37%) in the TOP/NIC group (p = .056). Pairwise comparisons showed a difference between TOP/NIC and PLC (p = .042) and a nonsignificant difference between TOP and PLC (p = .18). The PLC group gained 0.37 lb/week, the TOP group lost 0.41 lb/week, and the TOP/NIC group lost 0.07 lb/week (p = .004). Pairwise comparisons showed a difference between TOP and PLC (p < .001) and between TOP/NIC and PLC groups (p = .035). Paresthesia was more frequent in subjects on TOP than PLC (p = .011).. TOP, alone or in combination with the NIC, resulted in a numerically higher quit rate than PLC and decreased weight. A larger, PLC-controlled trial is needed to confirm these findings.

Topics: Adult; Body Weight; Counseling; Female; Fructose; Humans; Male; Middle Aged; Patient Compliance; Smoking Cessation; Tobacco Use Cessation Devices; Topiramate; Treatment Outcome

In randomised trials of medical interventions, the most reliable analysis follows the intention-to-treat (ITT) principle. However, the ITT analysis requires that missing outcome data have to be imputed. Different imputation techniques may give different results and some may lead to bias. In anti-obesity drug trials, many data are usually missing, and the most used imputation method is last observation carried forward (LOCF). LOCF is generally considered conservative, but there are more reliable methods such as multiple imputation (MI).. To compare four different methods of handling missing data in a 60-week placebo controlled anti-obesity drug trial on topiramate.. We compared an analysis of complete cases with datasets where missing body weight measurements had been replaced using three different imputation methods: LOCF, baseline carried forward (BOCF) and MI.. 561 participants were randomised. Compared to placebo, there was a significantly greater weight loss with topiramate in all analyses: 9.5 kg (SE 1.17) in the complete case analysis (N = 86), 6.8 kg (SE 0.66) using LOCF (N = 561), 6.4 kg (SE 0.90) using MI (N = 561) and 1.5 kg (SE 0.28) using BOCF (N = 561).. The different imputation methods gave very different results. Contrary to widely stated claims, LOCF did not produce a conservative (i.e., lower) efficacy estimate compared to MI. Also, LOCF had a lower SE than MI.

Topics: Anti-Obesity Agents; Body Weight; Data Interpretation, Statistical; Fructose; Humans; Obesity; Topiramate; Treatment Outcome

A 56-week randomized controlled trial was conducted to evaluate safety and efficacy of a controlled-release combination of phentermine and topiramate (PHEN/TPM CR) for weight loss (WL) and metabolic improvements. Men and women with class II and III obesity (BMI ≥ 35 kg/m(2)) were randomized to placebo, PHEN/TPM CR 3.75/23 mg, or PHEN/TPM CR 15/92 mg, added to a reduced-energy diet. Primary end points were percent WL and proportions of patients achieving 5% WL. Secondary end points included waist circumference (WC), systolic and diastolic blood pressure (BP), fasting glucose, and lipid measures. In the primary analysis (randomized patients with at least one postbaseline weight measurement who took at least one dose of assigned drug or placebo), patients in the placebo, 3.75/23, and 15/92 groups lost 1.6%, 5.1%, and 10.9% of baseline body weight (BW), respectively, at 56 weeks (P < 0.0001). In categorical analysis, 17.3% of placebo patients, 44.9% of 3.75/23 patients, and 66.7% of 15/92 patients, lost at least 5% of baseline BW at 56 weeks (P < 0.0001). The 15/92 group had significantly greater changes relative to placebo for WC, systolic and diastolic BP, fasting glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The most common adverse events were paresthesia, dry mouth, constipation, dysgeusia, and insomnia. Dropout rate from the study was 47.1% for placebo patients, 39.0% for 3.75/23 patients, and 33.6% of 15/92 patients. PHEN/TPM CR demonstrated dose-dependent effects on weight and metabolic variables in the direction expected to be beneficial with no evidence of serious adverse events induced by treatment.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Body Weight; Delayed-Action Preparations; Drug Combinations; Female; Fructose; Humans; Lipoproteins, LDL; Male; Middle Aged; Obesity, Morbid; Phentermine; Topiramate; Weight Loss; Young Adult

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.

Topics: Adult; Anticonvulsants; Body Mass Index; Body Weight; Cognition; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Neuropsychological Tests; Time Factors; Topiramate; Treatment Outcome

This 12-week open label study explored cognitive and seizure outcomes of 53 children treated with topiramate (TPM). The digit symbol test and verbal learning memory test were administered at baseline and study endpoint. Topiramate was started either in monotherapy or add-on therapy. Overall, 57% of children experienced a ≥50% seizure reduction, 36% became seizure free and cognitive testing revealed no significant changes during TPM therapy. Due to the heterogeneity of the study population, post hoc analyses were added to compare patients in initial or conversion to TPM monotherapy as well as patients who continued add-on therapy. Verbal learning memory test parameters showed neither significant differences within any subgroup comparing baseline with endpoint nor significant differences between described subgroups except for one finding. The digit symbol test revealed no differences between each subgroup between baseline and endpoint. Comparing pre-post differences, TPM monotherapy was associated with better cognitive outcomes than treatment in add-on therapy. These results have to be interpreted with caution given the short study duration and the heterogeneity of the study population. Despite these limitations, our overall results suggest that treatment with topiramate is associated with improved seizure control without significant changes in cognitive functions at the low doses tested.

Topics: Adolescent; Anticonvulsants; Body Weight; Child; Cognition Disorders; Dose-Response Relationship, Drug; Epilepsy; Female; Fructose; Humans; Male; Memory Disorders; Neuropsychological Tests; Prospective Studies; Psychiatric Status Rating Scales; Seizures; Severity of Illness Index; Single-Blind Method; Time Factors; Topiramate; Verbal Learning

The primary objective of this study was to compare the efficacy and tolerability of topiramate and amitriptyline in the prophylaxis of episodic migraine headache.. This was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority study. Adults with 3 to 12 migraines per month were randomized in a 1:1 ratio to receive an initial dose of 25 mg/d of either topiramate or amitriptyline, subsequently titrated to a maximum of 100 mg/d (or the maximum tolerated dose). The primary efficacy outcome was the change from prospective baseline in the mean monthly number of migraine episodes. Secondary efficacy variables included changes from the prospective baseline phase to the end of the double-blind phase in the mean monthly (28-day) rate of days with migraine, mean monthly rate of days with headache (migraine and nonmigraine), mean monthly rate of acute abortive medication use, mean monthly migraine duration, and mean monthly migraine severity. Additional secondary efficacy variables included changes in the mean monthly severity of migraine-associated symptoms (photophobia, phonophobia, and nausea), change in the mean monthly frequency f migraine-associated vomiting, and response rates (based on monthly migraine days and total headache days). The Migraine-Specific Quality of Life Questionnaire (MSQ) and the Weight Satisfaction Scale Questionnaire, which measures subjective satisfaction with current weight, were administered. Treatment-emergent adverse events (TEAEs) were monitored through the end of double-blind treatment.. The intent-to-treat population included 331 subjects (172 topiramate, 159 amitriptyline; 84.9% female; 84.6% white; mean [SD] age, 38.8 [11.0] years; mean weight, 77.1 [20.1] kg) who provided at least 1 efficacy assessment. The least squares mean (LSM) change from baseline in the mean monthly number of migraine episodes was not significantly different between the topiramate and amitriptyline groups (-2.6 and -2.7, respectively; 95% CI, -0.6 to 0.7). There were no significant differences between treatment groups in any of the prespecified secondary outcome measures. Subjects receiving topiramate had a significantly greater improvement in mean functional disability scores during migraine attacks compared with amitriptyline (LSM change: -0.33 vs -0.19; 95% CI, -0.3 to 0.0; P = 0.040) and in the role function-restrictive, role function-preventive, and emotional function domains of the MSQ (P = 0.012, P = 0.014, and P = 0.029, respectively). Subjects receiving topiramate had a mean weight loss of 2.4 kg, compared with a mean weight gain of 2.4 kg in subjects receiving amitriptyline. Subjects in the topiramate group reported an overall improvement from baseline in weight satisfaction, whereas the amitriptyline group reported an overall deterioration in weight satisfaction (P < 0.001, topiramate vs amitriptyline). TEAEs of mild or moderate severity were reported in 118 subjects (66.7%) in the topiramate group and 112 subjects (66.3%) in the amitriptyline group. Among the most common TEAEs (reported in +/-5% of subjects during the double-blind phase) in the topiramate group were paresthesia (29.9%), fatigue (16.9%), somnolence (11.9%), hypoesthesia (10.7%), and nausea (10.2%). The most commonly reported TEAEs in the amitriptyline group were dry mouth (35.5%), fatigue (24.3%), somnolence (17.8%), weight increase (13.6%), dizziness (10.7%), and sinusitis (10.7%).. In this noninferiority study, topiramate was at least as effective as amitriptyline in terms of reducing the rate of mean monthly migraine episodes and all prespecified secondary efficacy end points. Topiramate was associated with improvement in some quality-of-life indicators compared with amitriptyline and was associated with weight loss and improved weight satisfaction.

Topics: Adult; Amitriptyline; Body Weight; Central Nervous System Agents; Disability Evaluation; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Patient Satisfaction; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Topiramate; Treatment Outcome; United States

Treatment for binge-eating disorder (BED) is directed towards either the physical or psychopathological impairments, and often does not cover all the alterations characterizing the disease. In 30 BED patients, we monitored the effects of three types of 6-month treatment, randomly assigned to one of the three treatment groups, each consisting of 10 patients. Group 1 received a 1700-kcal diet (21% proteins, 27% lipids, 52% carbohydrate), cognitive-behavioural therapy (CBT), sertraline (50-150 mg/day) and topiramate (25-150 mg/day); group 2 received the same diet, CBT, sertraline; and group 3 received nutritional counselling and CBT. Binge frequency and weight were assessed every month. The Eating Disorder Inventory-2, the Symptoms Check List-90-Revised (SCL-90-R) and the Personality Diagnostic Questionnaire-4-Revised (PDQ-4-R) were administered before and after treatment. Binge frequency and excessive weight decreased significantly only in group 1 patients, in whom improvement was noted in total Eating Disorder Inventory-2 scores and the subitems 'bulimia', 'drive for thinness', 'maturity fear', 'ascetism', in total SCL-90-R scores and in the subitem 'somatization', in PDQ-4-R subitems 'schizotypic personality' and 'dependent personality'. Group 2 patients improved on the SCL-90-R subitems 'depression' and 'interpersonal relationship' and in the PDQ-4-R 'schizoid personality'. Combination therapy seems to be the only fully effective treatment in BED patients.

Topics: Anti-Obesity Agents; Binge-Eating Disorder; Body Weight; Cognitive Behavioral Therapy; Combined Modality Therapy; Counseling; Diet, Reducing; Female; Fructose; Humans; Middle Aged; Selective Serotonin Reuptake Inhibitors; Sertraline; Topiramate

This prospective, observational, single arm, monocentric study explored efficacy and tolerability outcomes of rapid oral initiation of topimarate in children with difficult to treat epilepsy. The study population consisted of 19 multiply handicapped children (mean age 4.4 years, range 0.6-15.3 years). The observation period was 12 weeks and included 7 visits. The mean initial dose of topiramate was 1.1 mg/kg body weight/d (range: 0.66-2.67 mg/kg/d) following rapid titration. The mean final dose was 3.3 mg/kg/d (range 0.5-6.7 mg/kg/d). An at least 50% reduction of seizure frequency compared to baseline was observed in 9 of 19 patients (47.4%). Six patients (31.6%) had a slight reduction of seizure frequency (<50%) and 4 patients (21.1%) experienced an increase of seizure frequency. A total number of 29 adverse events were documented in 17 of 19 patients. Most frequently captured were fatigue (26.3% of patients), decreased appetite (15.8%) and psychiatric disturbances (15.8%). No serious adverse events were reported. These data might suggest that in certain clinical circumstances rapid dose escalation with topiramate followed by a low maintenance dose might be a good therapeutic option for pediatric patients with difficult to treat epilepsy.

Topics: Adolescent; Anticonvulsants; Body Weight; Child; Child, Preschool; Disabled Children; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Infant; Male; Observation; Prospective Studies; Severity of Illness Index; Topiramate; Treatment Outcome

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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Body Weight; Child; Drug Resistance; Drug Therapy, Combination; Endpoint Determination; Epilepsy; Female; Fructose; Humans; Male; Middle Aged; Prospective Studies; Seizures; Topiramate; Treatment Outcome

OBJECTIVES - To assess the efficacy of topiramate in the treatment of idiopathic intracranial hypertension (IIH) and to compare it with acetazolamide. METHODS - Fourty patients diagnosed as IIH and randomly assigned to treatment with either acetazolamide or topiramate were assessed prospectively. Improvement in the visual fields at the end of third, sixth and twelfth months were taken into consideration. RESULTS - The demographic, clinical features and the cerebrospinal fluid (CSF) pressure of the two treatment groups were similar at the beginning of the study. When the follow-up visual field grades were compared with the visual field grades at the beginning of the study in each group a statistically significant improvement was detected with both drugs. When the results of the two treatment groups were compared with each other no statistically significant difference was present. Prominent weight loss was recorded in the topiramate group. CONCLUSIONS - Topiramate seems to be effective in the treatment of IIH. Weight reduction as well as the reduction of the CSF formation is the possible mechanism of action.

Topics: Acetazolamide; Adolescent; Adult; Anticonvulsants; Body Weight; Carbonic Anhydrase Inhibitors; Cerebrospinal Fluid Pressure; Female; Fructose; Humans; Male; Middle Aged; Prospective Studies; Pseudotumor Cerebri; Topiramate; Treatment Outcome; Vision Disorders; Visual Fields; Weight Loss

Borderline personality disorder (BPD) is a complex mental disease associated with severe serious functional impairment, affective instability, and impulsive aggression. The aim of this study was to compare the efficacy of topiramate versus placebo in the treatment of aggression in men with borderline personality disorder.. We conducted an 8-week, double-blind, placebo-controlled study of topiramate in 42 male subjects (42 of 44) meeting DSM-IV criteria for BPD. The Structured Clinical Interview (SCID I and II) was carried out. The subjects were randomly assigned to topiramate (n = 22) or placebo (n = 20).. Significant changes on four STAXI scales (State Anger, p < .01; Trait Anger, p < .05; Anger Out, p < .01; Anger Control, p < .01) were observed in the subjects treated with topiramate. A nonsignificant difference was found on the Anger In scale (p = .86). Additional significant weight loss was observed (difference in weight loss between the both groups was 5.0 kg, p < .01, 95% confidence interval = [-6.5 to 3.4]). All subjects tolerated topiramate relatively well.. Topiramate appears to be an effective agent in the treatment of anger in men with BPD. Mild weight loss can be expected.

Topics: Adult; Aggression; Body Weight; Borderline Personality Disorder; Double-Blind Method; Follow-Up Studies; Fructose; Humans; Male; Mood Disorders; Neuroprotective Agents; Personality Inventory; Placebos; Psychiatric Status Rating Scales; Statistics, Nonparametric; Topiramate

Topiramate was assessed in an open-label trial as broad-spectrum antiepileptic monotherapy, independently from the epilepsy type or syndrome. Adults and children aged 2 years and older, who were diagnosed with epilepsy within the last 5 years, treatment-naive or failing prior treatment with one antiepileptic drug (AED), received individually adjusted doses of topiramate, after escalation to 100mg/day over 4 weeks (maximum 400mg/day) or 3mg/kg/day over 6 weeks (maximum 9 mg/kg/day), respectively. Patients were followed for >or=7 months and optionally up to a maximum of 13 months. Data were analysed for all patients (n=692), as well as for focal (n=421) and generalized epilepsies (n=148). The median topiramate dose used was 125 mg/day in adults and 3.3mg/kg/day in children (or=50% reduction in mean monthly seizure frequency. Patients with focal and generalized epilepsies alike responded to treatment (73.9 and 83.8% with at least 50% seizure reduction): 39.4% of patients with focal epilepsy and 61.5% of those with generalized epilepsy were seizure-free. The mean monthly seizure frequency was significantly reduced versus baseline at all visits (p<0.001). Similar response rates were obtained from the 237 patients completing the 1-year observation period. During the mandatory 7-month period of study, 8.8% of patients reported insufficient tolerability as a reason for dropout. The most frequent adverse event was paraesthesia. Our results support findings that emerge from controlled studies that topiramate is effective and well tolerated when used as initial or second monotherapy. They also suggest that in a naturalistic setting, overall good retention on treatment and seizure freedom are observed at low doses in a broad spectrum of epilepsies.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Body Weight; Child; Child, Preschool; Epilepsy; Female; Fructose; Humans; Infant; Male; Middle Aged; Patient Satisfaction; Topiramate

To evaluate the effect of topiramate in elderly patients with onset of epilepsy after the age of 60, treatment-naive or non-responding to an initial antiepileptic drug.. Analysis of patients with epilepsy diagnosed in the preceding 5 years, aged>/=65 years (n=43), enrolled in a larger open-label trial (n=692). After titration to topiramate 100 mg/day over 4 weeks, the dose was adjusted according to individual response (maximum 400 mg/day). Patients were followed up for at least 7 months.. After 7 months, 79% of patients remained in the study. Seizure frequency decreased significantly vs baseline (P<0.001); >/=50% reduction in seizure frequency was achieved in 87% of patients, 64% remained seizure-free. Both previously treated and naive patients responded. Fourteen per cent dropped out because of insufficient tolerability. No unexpected or unusual adverse events were observed.. The results indicate that elderly patients respond well to topiramate monotherapy. The high patient retention rate reflects a favourable tolerability profile in this population.

Topics: Age of Onset; Aged; Aged, 80 and over; Anticonvulsants; Body Weight; Epilepsy; Female; Fructose; Humans; Male; Prospective Studies; Topiramate; Treatment Outcome

This randomized, double-blind, placebo-controlled UK trial evaluated the effect of topiramate as add-on therapy on seizure frequency, seizure severity, and quality of life in patients with epilepsy and intellectual disability. There were three phases: 4 weeks baseline, 18 weeks titration to 200-400 mg topiramate/day (adults) or 5-9 mg/kg/day (children), 12 weeks maintenance. Recruitment was low (88/120); analyses were underpowered. Seizure frequency varied enormously (median 17.7, maximum 1706.2). There was no significant difference in reduction in mean total seizure frequency or number of responders between the groups. Topiramate reduced seizure frequency by >30% from baseline (placebo 1%); post hoc analyses showed a trend toward significance (R ratio, P=0.052). There were no significant differences between the groups with respect to mean seizure severity or other outcome measures. Topiramate was generally well tolerated; body weight (P=0.015) and systolic blood pressure (P=0.043) were reduced. The study suggests that topiramate reduces seizure frequency in patients with epilepsy and intellectual disability without the added burden of behavior effects, and was potentially advantageous to physical well-being.

Topics: Adaptation, Psychological; Adult; Anticonvulsants; Body Weight; Double-Blind Method; Epilepsy; Female; Fructose; Humans; Intellectual Disability; Intelligence Tests; Male; Neuropsychological Tests; Quality of Life; Seizures; Sex Characteristics; Topiramate

The aim of this study was to further assess the long-term safety and effectiveness of open-label topiramate therapy in subjects with moderately to severely painful diabetic peripheral neuropathy (DPN).. Adults aged 18 to 75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an extension of a previously published randomized, double-blind trial comparing topiramate with placebo. Safety analyses included adverse event (AE) reports and clinical laboratory tests. Metabolic end points included body weight and glycosylated hemoglobin (HbA(1c)). Effectiveness analyses included a 100-mm pain visual analog (PVA) scale, worst and current pain severity, and sleep disruption.. Two hundred five subjects participated in this open-label extension study (118 formerly treated with topiramate and 87 who formerly received placebo). The groups did not differ in baseline demographics or disease characteristics. One hundred twenty-four (60.5%) subjects (68.6% of former topiramate recipients and 49.4% of former placebo recipients) completed the extension study; the most common reason for discontinuation was an AE (27.3% of subjects). AEs among subjects who received > or =1 dose of topiramate (n = 298) included upper respiratory tract infection (16.1%), anorexia (15.1%), diarrhea (12.8%), nausea (12.8%), paresthesia (10.7%), and headache (10.1%). Baseline pain scores were lower in those formerly treated with topiramate (n = 117) than in the former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs 2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs 4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption scores were not significantly different between the former topiramate and former placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025). Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the former topiramate and former placebo groups, respectively (P < 0.001 vs baseline). Mean HbA(1c) values before and after topiramate treatment were 7.7% and 7.4%, respectively, in the former topiramate group (P = 0.004 vs baseline), and 7.6% and 7.1%, respectively, in the former placebo group (P < 0.001 vs baseline).. Although 39.5% of subjects discontinued, most often due to AEs, the results of this 26-week, open-label extension study with topiramate (up to 600 mg/d) in subjects with moderately to severely painful DPN suggest that pain relief was effective and durable.

Topics: Adolescent; Adult; Aged; Anorexia; Anticonvulsants; Body Weight; Diabetic Neuropathies; Diarrhea; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Pain; Pain Measurement; Respiratory Tract Infections; Sleep Deprivation; Time Factors; Topiramate

Using identical methods, three simultaneous placebo-controlled trials of topiramate for painful diabetic neuropathy (PDN) did not reach significance. This independent yet concurrent placebo-controlled trial used different methods to assess topiramate efficacy and tolerability in PDN.. This 12-week, multicenter, randomized, double-blind trial included 323 subjects with PDN and pain visual analog (PVA) score of at least 40 on a scale from 0 (no pain) to 100 (worst possible pain). Topiramate (n = 214) or placebo (n = 109) was titrated to 400 mg daily or maximum tolerated dose. Short-acting rescue analgesics were permitted only during the first 6 weeks.. Baseline characteristics were comparable between groups except for mean body weight (topiramate, 101.4 kg; placebo, 95.7 kg; p = 0.028). Twelve weeks of topiramate treatment reduced PVA scale score (from 68.0 to 46.2 mm) more effectively than placebo (from 69.1 to 54.0 mm; p = 0.038). Fifty percent of topiramate-treated subjects and 34% of placebo-treated subjects responded to treatment, defined as >30% reduction in PVA scale score (p = 0.004). Topiramate monotherapy also reduced worst pain intensity (p = 0.003 vs placebo) and sleep disruption (p = 0.020 vs placebo). Diarrhea, loss of appetite, and somnolence were the most commonly reported adverse events in the topiramate group. Topiramate reduced body weight (-2.6 vs +0.2 kg for placebo; p < 0.001) without disrupting glycemic control.. Topiramate monotherapy reduced pain and body weight more effectively than placebo in patients with painful diabetic neuropathy.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Appetite; Appetite Depressants; Body Weight; Diabetic Neuropathies; Double-Blind Method; Female; Fructose; Humans; Leg; Male; Middle Aged; Neuralgia; Patient Dropouts; Sleep Disorders, Intrinsic; Topiramate; Treatment Outcome

Migraine is a highly prevalent chronic neurologic disorder. Frequent headache attacks require prophylactic treatment, and side effects are limiting prescribing factors among traditional agents for migraine prophylaxis. Beta-blockers, antidepressants, calcium channel blockers, and anticonvulsants have been used since the 1960s, and their efficacy has been demonstrated in several controlled studies. However, weight gain commonly occurs with most of these drugs and makes adherence to treatment a troublesome issue for many patients. Topiramate is a new anticonvulsant with proven efficacy in migraine and other conditions, which reportedly confers weight loss in patients receiving doses up to 300 mg/day.. The aim of this study was to evaluate adherence, weight loss, tolerability, and response to topiramate in adult migraineurs receiving treatment in a tertiary care center.. During a 2,5-year period, all patients receiving topiramate for migraine were evaluated after 3 months of treatment. The parameters evaluated were adherence to treatment, frequency in reduction of attacks > 50%, the presence and amount of weight loss, and adverse events.. Among 175 patients included, 134 (76.6%) adhered to the regimen, whereas 4% interrupted before the 3-month evaluation and 19.4% did not return for follow-up. Among the 134 patients evaluated, 82 (61.2%) revealed headache-frequency reduction > 50%; 105 (78.4%) patients experienced weight loss (range 1-10 kg; average, 3.4 kg). The most frequent side effects were paresthesia (39.6%); emotional disturbances, including depression, irritability, and anxiety (17.9%); thinking impairment (12.7%); memory disturbances (12.7%); and altered taste (11.9%).. Despite methodologic limitations, we conclude that good adherence to topiramate in a "real-world" headache clinic occurred in most of the study participants. The majority of patients also experienced weight loss and reductions in headache frequency, with an acceptable side-effect profile.

Topics: Adult; Anticonvulsants; Body Weight; Female; Fructose; Humans; Male; Migraine Disorders; Topiramate

This study assessed the long-term effectiveness and tolerability of topiramate in binge-eating disorder (BED) with obesity.. Sixty-one patients with BED (DSM-IV-TR criteria) and obesity enrolled in a 14-week, single-center, randomized, double-blind, placebo-controlled study. Completers (N = 35) were offered participation in a 42-week, open-label extension trial of topiramate. Fifteen patients who received topiramate and 16 patients who received placebo in the double-blind study entered the open-label trial. Topiramate was titrated from 25 mg/day to a maximum of 600 mg/day. The primary endpoint was change from baseline to final visit in weekly binge frequency using the last observation carried forward for all patients who received topiramate. Baseline for patients receiving double-blind topiramate was the beginning of the controlled study; for patients receiving placebo, baseline was the beginning of the open-label trial. Open-label data were gathered from December 1998 to November 2000.. Forty-four patients (31 who received topiramate in the open-label trial plus 13 who received topiramate in the double-blind study only) received at least 1 dose of topiramate; 43 patients provided outcome measures at a median final dose of 250 mg/day. Mean weekly binge frequency declined significantly from baseline to final visit for all 43 patients (-3.2; p < .001), for the 15 patients who received topiramate during the controlled and open-label studies (-4.0; p < .001), and for the 15 patients who received topiramate only during the open-label trial (-2.5; p = .044). Patients also exhibited statistically significant reduction in body weight. The most common reasons for topiramate discontinuation were protocol nonadherence (N = 17) and adverse events (N = 14).. Topiramate treatment was associated with enduring improvement in some patients with BED and obesity but was also associated with a high discontinuation rate.

Topics: Adolescent; Adult; Anticonvulsants; Body Mass Index; Body Weight; Bulimia; Comorbidity; Double-Blind Method; Drug Administration Schedule; Fructose; Humans; Longitudinal Studies; Middle Aged; Obesity; Obsessive-Compulsive Disorder; Patient Compliance; Patient Dropouts; Placebos; Topiramate; Treatment Outcome

At a tertial referral epilepsy centre 39 children were consecutively enrolled in an open add-on study with topiramate (TPM). All children had intractable epilepsy; the mean seizure frequency was 36 per month, and 31 children were treated with polypharmacy. All but five children were mentally retarded. The initial dose of TPM was 0.5-1 mg/kg daily, slowly titrated with 1-3 mg/kg daily every second week with an estimated target dose of 10 mg/kg daily. At latest follow-up 19 children continued on TPM, three (8%) were seizure-free, eight (21%) had a seizure reduction of more than 50% and eight (21%) improved their general condition. Mean follow-up was 13 months (range 9-36 months). Seizure reduction was seen in focal as well as generalized epilepsies. Adverse effects were reported in 21 cases (54%), weight loss and sedation being most frequent. The mean steady state dose in the children continuing on TPM was at latest follow-up: 14 mg/kg daily (< 5 years), 10 mg/kg daily (5-7 years), 5.8 mg/kg daily (8-17 years). The corresponding plasma level varied from 3 to 45 mumol/litre, and a significant correlation between the daily dose in mg/kg and the plasma level was found. Two patients with progressive myoclonus epilepsy are described separately; one had a dramatic general improvement. It is concluded that TPM seems to be a promising new broad-spectrum anti-epileptic drug, which is efficacious even in epilepsy syndromes, intractable to other new anti-epileptic drugs such as vigabatrin and lamotrigine.

Topics: Adolescent; Anticonvulsants; Body Weight; Child; Child, Preschool; Dose-Response Relationship, Drug; Epilepsies, Myoclonic; Epilepsy; Female; Fructose; Humans; Male; Topiramate; Treatment Outcome

The environmental psychological stress causes depressive disorders. Stress causes many neurobiological, neurodegenerative changes in brain. Topiramate (TPM) is used in the treatment of epilepsy and psychiatric diseases. However, there are conflicting findings that TPM disrupts cognitive functions. We aimed to investigate the effects of TPM on depression, anxiety, learning and memory as well as neurobiological, morphological changes in rats exposed to chronic unpredictable mild stress (CUMS). After CUMS was formed by random application of nine mild stressors for 45 days, TPM (at doses of 0.1, 1, 10, 100 mg/kg) was administered for 21 days. Sucrose preference, locomotor activity, forced swimming, elevated plus maze and Morris water maze tests were performed. Corticosterone, BDNF (Brain-derived neurotrophic factor) and glutamate levels and volumes of hippocampus were evaluated. Body weights of the rats were measured. Immobilization time increased in CUMS, CUMS + TPM0.1 in forced swimming test and time spent in platform quadrant increased in Control + TPM1, CUMS, CUMS + TPM0.1, CUMS + TPM1 in Morris water maze test. Control + TPM1 decreased distance to platform in Morris water maze while CUMS + TPM100 increased. Learning is impaired in CUMS + TPM100 while it is improved in Control + TPM1. BDNF levels increased in CUMS and glutamate levels increased in CUMS, CUMS + TPM10. Body weight decreased in CUMS, CUMS + TPM0.1, CUMS + TPM1, CUMS + TPM100. Hippocampus volumes increased in CUMS. In conclusion, CUMS improved cognition and this finding was supported by the increase of BDNF levels and volume of hippocampus. TPM 1 mg/kg improved cognition in non-stressed rats. TPM 0.1 and 1 mg/kg improved while TPM 100 mg/kg impaired memory in rats exposed to stress.

Topics: Animals; Behavior, Animal; Body Weight; Brain-Derived Neurotrophic Factor; Cognition; Corticosterone; Disease Models, Animal; Glutamic Acid; Hippocampus; Humans; Locomotion; Male; Morris Water Maze Test; Rats, Wistar; Stress, Psychological; Topiramate

Oxcarbazepine (OXC) is almost completely metabolized to its10-monohydroxy derivative (MHD), which is responsible for the pharmacological effects of the drug. Several studies have described the population pharmacokinetics (PPK) of MHD in pediatric patients, but little is known about its pharmacokinetics in adult patients. In addition, no study to date has proposed a model to investigate the influence of genetic polymorphisms on MHD pharmacokinetics. The aim of this study was to establish a PPK model of MHD to investigate the effects of genetic polymorphisms in UGT2B7, UGT1A9, ABCB1, and ABCB2 in adult Chinese patients with epilepsy and to develop a new dosage guideline for OXC.. Data were prospectively collected from 187 adult patients with epilepsy who were taking OXC. MHD trough concentrations were detected by enzyme-multiplied immunoassay. Patients were genotyped for 4 single nucleotide polymorphisms (UGT2B7 802T>C, UGT1A9 I399C>T, ABCB1 3435C>T, and ABCB2 1249G>A). Other covariates included sex, age, body weight (BW), hepato-renal function, and concomitant medications. Data were analyzed using the nonlinear mixed effects modelling software.. The apparent clearance (CL) of MHD was significantly influenced by glomerular filtration rate and BW, and was unrelated to other covariates such as genetic polymorphisms and coadministration with levetiracetam, lamotrigine, and topiramate. Moreover, a new dosage guideline was proposed based on the final model to individualize OXC regimens for adult patients with varying BW and renal function.. Glomerular filtration rate was first found as an important covariate influencing MHD CL. A PPK model was established to estimate the individual MHD CL for adult patients taking OXC and may be applied for individualizing doses in the target population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Asian People; Body Weight; Drug Monitoring; Epilepsy; Female; Genotype; Glomerular Filtration Rate; Humans; Kinetics; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Polymorphism, Single Nucleotide; Topiramate; Young Adult

To compare the effectiveness of weight-management medications used to assist with weight loss in real-world clinical practice in the Veterans Health Administration (VHA).. Retrospective, multicenter, observational cohort study.. National VA Corporate Data Warehouse.. A total of 66,035 VA patients aged 18 years or older with a body mass index of 25 kg/m. The primary outcome was the percentage change in weight from baseline to at least 20 weeks or later (i.e., closest weight to 6 months). Secondary outcomes were difference in the percentage of weight loss at 12 and 36 weeks; changes in blood pressure, hemoglobin A. In the VA population, the effectiveness of four available weight-management medications was similar. Patients receiving phentermine-topiramate had a greater proportion of weight loss after at least 20 weeks compared with those solely enrolled in the VA's MOVE! weight-management program.

Topics: Adult; Aged; Anti-Obesity Agents; Benzazepines; Body Weight; Cohort Studies; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Obesity; Orlistat; Phentermine; Retrospective Studies; Topiramate; United States; United States Department of Veterans Affairs; Weight Loss

Intellectual disability (ID) is associated with weight gain caused by antiepileptic drugs such as valproic acid. The present study analyzed the relationship between ID and weight loss caused by topiramate (TPM).. Seventy-eight patients with epilepsy (35 women, aged 18 to 70years) were enrolled in this prospective study. Body weight was measured before and 1, 6, 12, and 18months after initiation of TPM treatment. Both patients and caregivers were provided information about TPM-related weight loss. The patients were divided into the group with no or mild ID (intelligence quotient >50) and the group with moderate to profound ID (intelligence quotient ≤50).. Body weight of both groups significantly decreased until 6months but stabilized after 12months. Weight loss at 6, 12, and 18months was significantly greater in the group with no or mild ID than in the group with moderate to profound ID. Body weight change at 18months was correlated with intellectual levels (β=0.274, p=0.011) and baseline body mass index (β=-0.322, p=0.002) by multiple linear regression analysis.. The present study suggests that the pattern of weight loss during TPM administration differs according to intellectual levels. Patients with ID maintained their body weight. Weight loss due to TPM might be weakened by caregiver control of food intake or inactivity.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Body Mass Index; Body Weight; Cohort Studies; Epilepsy; Female; Humans; Intellectual Disability; Male; Middle Aged; Prospective Studies; Topiramate; Weight Gain; Weight Loss; Young Adult

Management of epilepsy during pregnancy in a resource-limited setting (RLS) is challenging. This study aimed to assess obstetric outcomes and effects on babies of women with epilepsy (WWE) exposed to Anti-epileptic drugs (AEDs) compared to non-exposed controls in a RLS.. Pregnant WWE were recruited from antenatal and neurology clinics of a tertiary care hospitals in Sri Lanka. Patients were reviewed in each trimester and post-partum. Medication adherence, adverse effects, seizure control and carbamazepine blood levels were monitored. Post-partum, measurements for anthropometric and dysmorphic features of the babies and congenital abnormalities were recorded. Age and sex matched babies not exposed to AED recruited as controls were also examined.. Ninety-six pregnant WWE were recruited (mean period of gestation 22.9 weeks). Mean age was 28 years and 48(50%) were primigravidae. Fifty percent (48) were on monotherapy, while 23.8, 15.9 and 4.1% were on two, three and four AEDs respectively. AEDs in first trimester (TM1) were carbamazepine (71%), valproate (25.8%) clobazam (29.5%), lamotrigine (7%) topiramate (5%) and others (3.4%). Sodium valproate use reduced significantly from T1 to T2(p < 0.05). Sub-therapeutic carbamazepine levels correlated positively (r = 0.547) with poor medication adherence (p = 0.009) and negatively (r = 0.306) with adverse effects (p = 0.002). Seventy-six WWE completed follow-up reporting w 75 (98.6%) live births and one T1 miscarriage (1.3%). Three (4.3%) were preterm. Majority (73.33%) were normal vaginal deliveries. Cesarean sections were not increased in WWE. Fifty-nine (61.45%) babies were examined. For those examined during infancy, 53 age and sex matched controls were recruited and examined.. Congenital abnormalities occurred in 5 (9.43%) babies of WWE [atrio-ventricular septal defect (2), renal hypoplasia (1), cryptorchidism (1), microcephaly (1)] compared to 2 (3.77%) in controls (2 microcephaly; p = 0.24). Fetal exposure to AEDs increased a risk of low birth weight (RR 2.8; p = 0.049). Anthropometric parameters of AED exposed babies were lower at birth but not statistically significant between the two groups (weight p = 0.263, length p = 0.363, occipito-frontal circumference (OFC) p = 0.307). However, weight (p = 0.009), length (p = 0.016) and OFC (p = 0.002) were significantly lower compared to controls at an average of 3.52 months.. Most pregnancies are unplanned in the RLS studied, and AEDs were altered during pregnancy. Congenital anomalies occurred at rates comparable to previous reports. Fetal exposure to AED had growth retardation in infancy compared to non-exposed babies.

Topics: Abortion, Spontaneous; Adolescent; Adult; Anticonvulsants; Body Height; Body Weight; Carbamazepine; Case-Control Studies; Child Development; Clobazam; Congenital Abnormalities; Developing Countries; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Lamotrigine; Live Birth; Medication Adherence; Pregnancy; Pregnancy Complications; Premature Birth; Prenatal Exposure Delayed Effects; Sri Lanka; Topiramate; Valproic Acid; Young Adult

Topiramate is commonly used for treating epilepsy in both children and adults. Recent clinical data suggests that administration of topiramate to women during pregnancy increases the risk of oral clefts in their offspring. To better understand the potential effects of topiramate, we dosed adult female zebrafish with topiramate, and investigated the altered morphologies in adult females and their offspring. It showed that topiramate-treated female fish had reduced oocyte maturation, and the survival rates of their offspring were seriously decreased during embryogenesis. In addition, around 23% of offspring displayed cartilage malformation in the craniofacial area, such as loss of ceratobranchial cartilages as well as impaired ceratohyal, Meckel's cartilage and ethmoid plate development. Moreover, mineralization of ceratohyal, Meckel's cartilage, and vertebrae were downregulated during bone development. Taken together, we concluded that topiramate impaired oogenesis in the maternal reproductive system, and then caused offspring cartilage malformation or bone dysplasia.

Topics: Animals; Body Weight; Chondrogenesis; Craniofacial Abnormalities; Female; Fructose; Models, Animal; Oocytes; Oogenesis; Teratogenesis; Teratogens; Topiramate; Zebrafish

Topiramate is a second-generation antiepileptic drug used as monotherapy and adjunctive therapy in adults and children with partial seizures. A population pharmacokinetic (PPK) analysis was performed to improve the topiramate dosage adjustment for individualized treatment.. Patients whose steady-state serum concentration of topiramate was routinely monitored at Kyoto University Hospital from April 2012 to March 2013 were included in the model-building data. A nonlinear mixed effects modeling program was used to evaluate the influence of covariates on topiramate pharmacokinetics. The obtained PPK model was evaluated by internal model validations, including goodness-of-fit plots and prediction-corrected visual predictive checks, and was externally confirmed using the validation data from January 2015 to December 2015.. A total of 177 steady-state serum concentrations from 93 patients were used for the model-building analysis. The patients' age ranged from 2 to 68 years, and body weight ranged from 8.6 to 105 kg. The median serum concentration of topiramate was 1.7 mcg/mL, and half of the patients received carbamazepine coadministration. Based on a one-compartment model with first order absorption and elimination, the apparent volume of distribution was 105 L/70 kg, and the apparent clearance was allometrically related to the body weight as 2.25 L·h·70 kg without carbamazepine or phenytoin. Combination treatment with carbamazepine or phenytoin increased the apparent clearance to 3.51 L·h·70 kg. Goodness-of-fit plots, prediction-corrected visual predictive check, and external validation using the validation data from 43 patients confirmed an appropriateness of the final model. Simulations based on the final model showed that dosage adjustments allometrically scaling to body weight can equalize the serum concentrations in children of various ages and adults.. The PPK model, using the power scaling of body weight, effectively elucidated the topiramate serum concentration profile ranging from pediatric to adult patients. Dosage adjustments based on body weight and concomitant antiepileptic drug help obtain the dosage of topiramate necessary to reach an effective concentration in each individual.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Asian People; Body Weight; Carbamazepine; Child; Child, Preschool; Drug Monitoring; Epilepsy; Female; Fructose; Humans; Male; Middle Aged; Models, Biological; Monitoring, Physiologic; Phenytoin; Seizures; Topiramate; Young Adult

Phentermine/topiramate combination therapy resulted in significant weight loss and improvements in cardiometabolic risk factors in patients with obesity/overweight in two published 56-week randomized, placebo-controlled trials (EQUIP and CONQUER). The purpose of the current study was to examine whether phentermine/topiramate is also associated with greater improvements in health-related quality of life (HRQOL) and whether HRQOL improvements are solely attributable to weight reduction.. Patients in EQUIP (n = 751) had a body mass index (BMI) ≥ 35 with no obesity-related comorbidity. Patients in CONQUER (n = 1623) had a BMI ≥ 27 and ≤ 45 and at least two obesity-related comorbid conditions. HRQOL was assessed with Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and Medical Outcomes Study Short Form (SF-36) (CONQUER only).. Significant improvements in both obesity-specific and physical HRQOL were observed at 56 weeks in both trials (p < .0001). In EQUIP, BMI reduction fully mediated improvements in IWQOL-Lite total score (p < .0001). In CONQUER, both BMI reduction (all p values < .0001) and change in depressive symptoms (all p values < .025) were significant mediators of improved IWQOL-Lite total score and SF-36 Physical Component Summary score. Gender, psychiatric history, and baseline triglycerides moderated these relationships.. Both trials demonstrated that treatment with phentermine/topiramate improved HRQOL compared with placebo. Although reduction in BMI accounted for the majority of improvements in obesity-specific and physical HRQOL, decrease in depressive symptoms was also a significant mediator. Results highlight the predominance of weight reduction as a key factor in improving HRQOL in obesity.

Topics: Adult; Body Mass Index; Body Weight; Depression; Female; Fructose; Health Status; Humans; Male; Middle Aged; Obesity; Outcome Assessment, Health Care; Phentermine; Quality of Life; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Topiramate; Weight Loss

Medications for use as an adjunct to lifestyle modification therapy (LSM) for severe adolescent obesity are limited. Topiramate results in weight reduction in adults with obesity, but has not been studied in adolescents.. To examine the effect of topiramate plus LSM on body mass index (BMI) reduction in adolescents with severe obesity.. Data for this retrospective chart review were collected from patients attending a pediatric weight management program who were treated with LSM plus topiramate for 3 months minimum. Mean BMI percent change from baseline was evaluated using t-tests.. Twenty-eight patients (mean age 15.2 ± 2.5 years, mean baseline BMI 46.2 ± 10.3 kg/m(2)) were identified for inclusion. The 6-month percent change in BMI was -4.9, 95% confidence interval (-7.1, -2.8), P < .001.. Topiramate with concurrent LSM was associated with clinically meaningful BMI reduction in adolescents with severe obesity. Randomized controlled clinical trials examining efficacy and safety of topiramate for severe obesity in adolescents are needed.

Topics: Adolescent; Anti-Obesity Agents; Body Mass Index; Body Weight; Female; Fructose; Humans; Male; Obesity, Morbid; Retrospective Studies; Topiramate; Treatment Outcome; Weight Loss

There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models.

Topics: Absorptiometry, Photon; Administration, Oral; Alkaline Phosphatase; Animals; Anticonvulsants; Biomechanical Phenomena; Body Composition; Body Weight; Bone and Bones; Bone Density; Bone Morphogenetic Protein 2; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Fructose; Lamotrigine; Male; Models, Animal; Orchiectomy; Osteoprotegerin; Peptide Fragments; Peptides; Procollagen; Rats; Rats, Wistar; Statistics, Nonparametric; Topiramate; Triazines

Weight loss is one of the most frequent side effects of topiramate treatment. The aim of our study was to investigate the effect of topiramate on body mass index, serum glucose, insulin, cortisol, leptin, and neuropeptide-Y levels and the role of these variables on the pathogenesis of weight loss in prepubertal children with epilepsy.. Twenty prepubertal children with epilepsy who were treated with topiramate were enrolled in the study. Topiramate was used at a daily dose of 5 mg/kg. Body mass index and fasting insulin-to-glucose ratio were calculated. Serum glucose, insulin, leptin, neuropeptide-Y, ghrelin, and cortisol levels were measured for all patients before the treatment and at the third and sixth months of the treatment.. There were significant decreases in mean body mass index, fasting insulin-to-glucose ratio, and serum cortisol and leptin levels at the third and sixth months of the treatment compared with pretreatment levels. No significant changes were observed in serum glucose, ghrelin, neuropeptide-Y, or insulin levels.. The exact mechanism of topiramate on energy balance regulation is not clearly understood. Topiramate affects body mass index, fasting insulin-to-glucose ratio, and serum leptin and cortisol levels in prepubertal children. These changes may be key factors in weight loss due to topiramate.

Topics: Anticonvulsants; Blood Glucose; Body Mass Index; Body Weight; Child; Child, Preschool; Epilepsy; Female; Fructose; Ghrelin; Humans; Hydrocortisone; Insulin; Leptin; Male; Neuropeptide Y; Topiramate

Reproductive endocrine disturbances are a major health concern in women with epilepsy due to their long term use of antiepileptic drugs (AEDs). Second generation AEDs such as topiramate (TPM) and gabapentin are frequently used for the treatment of epilepsy as well as migraine, bipolar disorder etc. Despite the widespread clinical complications, however the definitive mechanism(s) mediating the side effects of TPM and gabapentin remain obscure. The present study was aimed to evaluate the long term effects of TPM and gabapentin on reproductive functions in young female Wistar rats. Estrous cyclicity, ovarian histology as well as estradiol, LH, leptin and insulin hormones level were studied to elucidate the long-term effect of these AEDs monotherapy on reproductive functions in non-epileptic animals. Further to explore the effects on gonadotropin releasing hormone (GnRH) neuroendocrine plasticity, the expression of GnRH, gamma-amino butyric acid (GABA), glutamic acid decarboxylase (GAD), glial fibrilliary acidic protein (GFAP) and polysialylated form of neural cell adhesion molecule (PSA-NCAM) was studied in median eminence (ME) region of these animals by immunohistochemistry, Western blot hybridization and RT-PCR. Our results demonstrate that TPM and gabapentin treatment for 8 weeks cause reproductive dysfunction as ascertained by disturbed hormonal levels and estrous cyclicity as well as alterations in GABAergic system and GnRH neuronal-glial plasticity. Our findings suggest that treatment with TPM and gabapentin disrupts the complete hypothalamo-hypophyseal-gonadal axis (HPG) through GnRH pulse generator in hypothalamus.

Topics: Amines; Animals; Anticonvulsants; Astrocytes; Blotting, Western; Body Weight; Cyclohexanecarboxylic Acids; Enzyme-Linked Immunosorbent Assay; Estradiol; Estrous Cycle; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Gonadotropin-Releasing Hormone; Hypothalamus; Insulin; Leptin; Luteinizing Hormone; Ovary; Rats, Wistar; Reproduction; Reverse Transcriptase Polymerase Chain Reaction; Topiramate

Antiepileptic drugs may affect the endocrine system. We investigated the effects of valproic acid and topiramate on the levels of insulin, c-peptide and adipocytokines in pre-pubertal patients with idiopathic partial and generalized epilepsy.. Forty-one children with epilepsy were included. The patients were divided into two groups (valproic acid; n = 21, topiramate; n = 20). The weight, height, body mass index and homeostasis model assessment of insulin resistance (HOMA-IR) were recorded and insulin, c-peptide, leptin, neuropeptide Y, adiponectin, visfatin and resistin levels were determined at 0, 6 and 12 months of therapy.. In the valproate group, weight and height increased significantly. Seven of 21 patients were overweight at the end of one year. Leptin was higher in the overweight subgroup. Although insulin and HOMA-IR increased (p < 0.05), none of the patients showed hyperinsulinism or IR. Resistin had decreased at the 6th and 12th months (p < 0.05). In the topiramate group, some statistically nonsignificant changes were demonstrated.. The mechanisms behind valproate and topiramate-related weight control are still unclear, especially in children. Valproate and topiramate affect the weight, BMI, and insulin, leptin and adipocytokine levels in prepubertal children. We suggest that further studies including more patients with a long follow-up period are necessary to draw a firm conclusion regarding an association between the treatment with these drugs and the levels of leptin, insulin and adipocytokines.

Topics: Adiponectin; Anticonvulsants; Body Mass Index; Body Weight; C-Peptide; Child; Epilepsy; Female; Fructose; Humans; Insulin; Leptin; Male; Neuropeptide Y; Nicotinamide Phosphoribosyltransferase; Resistin; Topiramate; Valproic Acid

Topiramate is an anticonvulsant agent effective in the prophylaxis of migraine, which also induces weight reduction by an unknown mechanism. We investigated the effect of topiramate on resting metabolic rate, anthropometric measurements, and body composition in patients with migraine independently from any intention to lose body weight. Forty patients (18-71 years old) with migraine were treated with 100 mg of topiramate/day over a period of 3 months. Anthropometric measurements, body fat proportions and resting metabolic rates of these patients were measured before and after treatment. At the end of 3 months, we detected mean 0.8 kg reduction in body weight and 0.3 kg/m(2) reduction in body mass index (BMI). Waist circumference decreased significantly (p = 0.01). Body fat ratio decreased (p = 0.016). Abdominal skinfold measurements decreased after treatment (p = 0.048); however, no difference was found in other regions (p > 0.05). We did not find a significant difference in resting metabolic rate (p > 0.05).These TPM-treated patients lost weight and had reduction in their mean BMI. It was seen that patients lost weight from body fat tissue and central area. We saw that TPM'S weight-reducing effect was independent from resting metaobolic rate. The weight-reducing effect of TPM may result from changes on the hypothalamus.

Topics: Adolescent; Adult; Aged; Basal Metabolism; Body Composition; Body Weight; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Treatment Outcome; Weight Loss

Topiramate currently approved for marketing as antiepileptic drug also possesses anti-diabetic activity. The aim of this study was to determine the antidiabetic effect of topiramate in a rat model of diabetes mellitus. Diabetes was induced by a single injection of streptozotocin to fasted rats. Diabetic animals were divided into untreated; insulin treated; topiramate treated with 25, 50 and 100 mg/kg; and combined insulin plus topiramate treatment in the previous doses. All medications were given once daily started after the rise of blood glucose for three weeks. Control rats were divided into untreated; vehicle treated and rats given topiramate in the previous doses. Body weight, blood-glucose and insulin levels were measured. Histopathological examination, immunohistochemical and morphometric studies of islets of the pancreas were done. Topiramate 50 and 100mg/kg resulted in a significant decrease in the blood glucose and increase in the insulin levels as well as the number of islets and the count and mass of beta cells. Combined treatment to diabetic rats with insulin and topiramate induced a better response than either alone. Further experimental and clinical studies are needed to explore the different mechanisms of action of topiramate as antidiabetic both in insulin dependent and non-insulin-dependent diabetes mellitus.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Fructose; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Male; Rats; Rats, Sprague-Dawley; Topiramate

We investigated the mechanism of topiramate-related appetite loss and exposed its relationship to body weight, body mass index, body fat index, and serum insulin, lipid, leptin, neuropeptide-Y, cortisol, ghrelin, and adiponectin levels. Twenty children with epilepsy were evaluated at baseline and months 3 and 6 of treatment. Their body fat index, leptin, and neuropeptide-Y levels significantly decreased at month 3, whereas significant decreases occurred in body weight, body mass index, body fat index, neuropeptide-Y, cholesterol, and cortisol levels of patients at month 6 compared with baseline. Weight loss during topiramate treatment was attributed to loss of appetite and reduced food intake caused by reductions in neuropeptide-Y. To the best of our knowledge, this study is the first to describe reductions in neuropeptide-Y with topiramate use in humans.

Topics: Adiponectin; Adiposity; Anticonvulsants; Appetite; Body Mass Index; Body Weight; Child; Epilepsy; Female; Fructose; Ghrelin; Humans; Insulin; Leptin; Male; Neuropeptide Y; Topiramate

Both diet and medications are useful in the treatment of the obese patient. Weight loss of about 10% below baseline can be achieved with both, and there is no evidence that the composition of the diet, by itself, has any influence on weight loss. Presently only 1 drug is approved for long-term treatment of overweight patients, and its effectiveness is limited to palliation of the chronic disease of obesity. Combinations of medications and antidiabetic drugs that produce weight loss are being evaluated.

Topics: Adolescent; Adult; Anti-Obesity Agents; Antidepressive Agents, Second-Generation; Body Weight; Bupropion; Child; Drug Approval; Drug Combinations; Energy Intake; Exenatide; Female; Fructose; Humans; Hypoglycemic Agents; Islet Amyloid Polypeptide; Lactones; Male; Metformin; Naltrexone; Narcotic Antagonists; Obesity; Orlistat; Patient Compliance; Peptides; Randomized Controlled Trials as Topic; Sympathomimetics; Topiramate; United States; United States Food and Drug Administration; Venoms

Binge eating disorder (BED) is characterized by excessive food intake during a short period of time and is often associated with obesity. Mouse models of binge-like eating behavior are lacking making it difficult to employ genetic models in the identification of mechanisms regulating excessive eating. We report a rapid and simple model to induce binge-like eating behavior in mice that does not require food deprivation or exogenous stressors. Weekly 24 h access to a nutritionally complete high energy diet (HED), along with continuous access to standard chow, resulted in a significant increase in HED intake following its presentation compared to mice that had continuous access to both diets. Mice exhibiting binge-like eating consumed one-third of their normal total daily caloric intake within 2.5 h of HED presentation. Moreover, total 24-h caloric intakes were increased by 50% in mice exhibiting binge-like eating. Following repeated cycles, binge-like eating of the HED was maintained over several weeks with no evidence of habituation or significant alterations in body weight and adiposity. Pharmacological evaluation of binge-like eating behavior was performed using clinically employed compounds. Interestingly, binge-like eating was dose-dependently decreased by fluoxetine, but not baclofen or topiramate. These data support clinical validation of this mouse model of binge-like eating behavior, as fluoxetine has been shown to reduce binge frequency in human subjects with BED. The availability of transgenic and knockout mice will allow for the determination of genes that are involved in the initiation and maintenance of binge-like eating behavior.

Topics: Adiposity; Animals; Anti-Obesity Agents; Baclofen; Behavior, Animal; Binge-Eating Disorder; Body Weight; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Energy Intake; Fluoxetine; Fructose; GABA-B Receptor Agonists; Habituation, Psychophysiologic; Male; Mice; Mice, Inbred C57BL; Selective Serotonin Reuptake Inhibitors; Topiramate

We aimed to investigate the effects of topiramate monotherapy on anthropometric indexes, insulin resistance, and serum leptin and lipid levels in 33 premenopausal women (mean age+/-standard deviation: 26.7+/-7.1years) with cryptogenic epilepsy. Body mass index (BMI), waist circumference and serum leptin, insulin and lipid levels were measured at baseline and at 6months after initiation of topiramate. We found reductions in BMI (p<0.001), waist circumference (p<0.001) and serum high-density lipoprotein (HDL) cholesterol levels (p=0.011). We also found significant improvements in insulin resistance (p=0.023), but not in serum leptin levels (p=0.45). Our results suggest that topiramate treatment in women with epilepsy is associated with reduced BMI and waist circumference and improvement in insulin resistance; however, according to our data, topiramate treatment is also associated with lower HDL cholesterol levels, which may substantially increase vascular disease.

Topics: Adolescent; Adult; Anthropometry; Anticonvulsants; Body Mass Index; Body Weight; Enzyme-Linked Immunosorbent Assay; Epilepsy; Female; Fructose; Humans; Insulin Resistance; Leptin; Lipid Metabolism; Topiramate; Young Adult

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.

Topics: Adolescent; Adult; Age Distribution; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Body Weight; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

To explore the mechanism of topiramate-induced weight loss in epilepsy children by monitoring metabolism indices.. Children with epilepsy were treated with topiramate at their first clinical visit. Metabolism indices including body mass index (BMI) and its SD scores, leptin, adiponectin, leptin/adiponectin (L/A), lipid profile-insulin and Homeostasis Model Assessments (HOMA) index were collected before and after treatment.. Topiramate treatment significantly reduced L/A (t = 2.156, p = 0.031), and markedly increased the serum level of adiponectin (t = 3.124, p = 0.002). Moreover, there were no relationships between the metabolism indices and dosages of topiramate (p > 0.05).. Our studies find that topiramate treatment in epilepsy children increases energy metabolism, resulting in weight loss. It has been demonstrated that adiponectin play a significant role in metabolic regulations.

Topics: Adiponectin; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Body Weight; Case-Control Studies; Child; Epilepsy; Female; Fructose; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolism; Statistics, Nonparametric; Topiramate

Topics: Anti-Obesity Agents; Antipsychotic Agents; Awareness; Body Weight; Bupropion; Clinical Competence; Fructose; Humans; Hypoglycemic Agents; Melatonin; Metformin; Obesity; Topiramate; Treatment Outcome; Weight Gain

The objectives of this study is to investigate the toxic effects of Artemisia herba Alba (300 mg/kg/ body wight) on the reproductive system after administration to female Sprague-Dawley rats weighting 250-300 g for two time periods 4 and 12 weeks. Twenty adult female rats were divided into two groups and exposed to Topiramate diet at a concentration of 300 mg/kg/body weight for two periods of time. First group containing 10 rats received treatment for 4 weeks and a second group of 10 rats received the same dose of treatment for a period of 12 weeks and compared with twenty non-exposed female rats received vehicle treatment. Female rats were allowed mating with males after 10 days prior to the last administration dose. Animals were autopsied under light anesthesia after mating and several parameters were determined including: Number of pregnant rats, body and reproductive organ weight, number of implantation sites, viable fetuses and resorption sites. Assessment of pregnancies in females was measured and the significance of these results was calculated using student's t and Chi-square tests. The effect of Artemisia herba alba exposure on fertility was assessed in terms of pregnant rats number, implantation sites, viable fetuses and resorption sites. Exposure to Artemisia herba alba for 4 weeks did not have much effect on fertility. Significant decrease in the relative ovarian weights and embryo weights in rats exposed to Artemisia herba alba were observed. Exposure to Artemisia herba alba for a 12 weeks resulted in a reduction in the percentage of pregnancies and in the number of implantation sites when compared with controls in both treatment periods. Rats receiving 12 weeks treatment showed an increase in ovarian weights and a decrease in viable fetus's number. These results indicate that long-term exposure of female rats to Artemisia herba Alba causes adverse effects on the reproductive system and fertility. The results of the current study suggest that ingestion of Artemisia herba alba by adult female rats causes adverse effects on fertility and reproduction.

Topics: Animals; Artemisia; Body Weight; Female; Fertility; Fructose; Organ Size; Ovary; Plant Extracts; Rats; Rats, Sprague-Dawley; Reproduction; Topiramate

Previous reports indicate that topiramate (TPM) might be an effective treatment for alcohol dependence, perhaps due to a decrease alcohol's rewarding effects resulting from inhibition mesocorticolimbic dopamine (DA) release. Additional reports indicate that TPM antagonizes chronic changes induced by alcohol at the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptors. In the present study, a C57BL/6 (B6) murine model (n = 40) was used to evaluate the effect of TPM on the consumption of 12% alcohol over a 21-h period.. TPM (0, 10, 30, 90 mg/kg) injected subcutaneously into B6 mice 60 min prior to access to a 12% ethanol solution (v/v) over 8 days produced dose-responsive reduction in consumption during the first 2-h period after injection.. Across the 8 days of treatment ethanol intake (g/kg) for SAL, T10, T30, and T90, respectively, was 1.34, 1.03, 0.72, and 0.67. This reduction appears to require systemically available TPM since it was not statistically supported when assessed over the entire 21-h period of ethanol availability. None of the TPM doses affected food consumption or body weight, and T90 dose did not reduce motor activity either by itself or in combination with ethanol.. Unlike previous experiments using the same B6 mouse model to assess naltrexone or tiagabine, there was no evidence that mice developed tolerance to the TPM-induced reductions in ethanol consumption. Thus, in the B6 mouse, TPM reduced ethanol intake at doses with no readily apparent adverse side effects, an effect consistent with recent clinical reports. Additional study will be directed toward characterizing TPM as a treatment for alcohol dependence.

Topics: Administration, Oral; Alcoholism; Animals; Anticonvulsants; Body Weight; Brain; Central Nervous System Depressants; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Drug Tolerance; Eating; Ethanol; Fructose; Injections, Subcutaneous; Mice; Mice, Inbred C57BL; Receptors, AMPA; Synaptic Transmission; Topiramate; Treatment Outcome

Topiramate (TPM) has an evident efficacy in the treatment of childhood epilepsy for multiple pharmacologic properties. However it was reported that it may cause adverse effects such as liver failure and hepatitis, which arouses the attention of the medical field. This study aimed to investigate the hepatotoxicity of low-dosage, high-dosage TPM or TPM along with valproate sodium (VPA) in aspects of biochemistry indexes, oxidative stress indexes and liver pathomorphology in young rats.. Sixty 3-week-old male Wistar rats were randomly assigned into five groups of 12 rats (Groups A-E). The rats in the experimental groups (Groups A-C) were administered intragastrically with TPM 40 mg/(kg.d), 80 mg/(kg.d) and TPM 40 mg/(kg.d) plus VPA 300 mg/(kg.d) respectively. The rats in the negative control group (Group D) were administered with the same volume of distilled water. The ones in the positive control group (Group E) were treated by injection of 10% carbon tetrachloride dissolved in olive oil subcutaneously at a dose of 5 mL/kg twice a week. After 3-month administration, the changes of body weight and liver pathomorphology were observed; biochemical markers in serum and indexes of oxidative stress in liver homogenate associated with hepatotoxicity were examined.. The body weights of rats in the experimental groups were significantly lower than that of rats in the negative control group. The levels of serum alanine aminotransferase, alkaline phosphatase and the content of malondialdehyde, and the activity of superoxide dismutase in liver tissues did not change significantly in the experimental groups. The contents of glutathion in the high dosage of TPM group (29.85 +/- 1.62 mg/g prot) or in the TPM plus VPA group (29.63 +/- 4.47 mg/g prot) were significantly reduced compared with those of the negative control group (33.09 +/- 1.69 mg/g prot) and that of the low dosage of TPM group (32.43 +/- 2.11 mg/g prot) (both P < 0.05). In the histopathological examination, extensive steatosis and diffuse punctate necrosis of hepatocytes distributed in the portal area were found by microscopy in the positive control group. There were granular degeneration of some hepatocytes near the central veins of hepatic lobules in the low dosage of TPM group and punctate necrosis of some hepatocytes in the high dosage of TPM group. In the TPM plus VPA group, histological examination showed granular degeneration and fatty degeneration of partial liver cells and punctate necrosis of some hepatocytes.. Long-term use of TPM can decrease antioxidant capacity of organism, resulting in slight pathological changes of liver tissues. High dosage of TPM or TPM along with VPA administration enhances the risk of the side effects.

Topics: Animals; Anticonvulsants; Body Weight; Dose-Response Relationship, Drug; Fructose; Glutathione; Lipid Peroxidation; Liver; Male; Rats; Rats, Wistar; Topiramate; Valproic Acid

To study the effects of topiramate (TPM) and valproate acid (VPA) on serum insulin and leptin levels in young and adult rats.. Thirty healthy female young rats (21 days old) and thirty healthy female adult rats (2 months old) were randomly administered with TPM (50 mg/kg daily), VPA (200 mg/kg daily) or normal saline (control group) by intragastric administration for 5 weeks. After 5 weeks, serum leptin and insulin levels were detected by radioimmunoassay (RIA).. Serum leptin and insulin levels in both the young and adult TPM groups were remarkably lower than those of the corresponding control group (P < 0.05). The adult TPM group had significantly lower serum leptin and insulin levels than the young TPM group (P < 0.05). In contrast, serum leptin and insulin levels in both the young and adult VPA groups were remarkably higher than those of the corresponding control group (P < 0.05). The young TPM group had significantly higher serum leptin and insulin levels than the adult TPM group (P < 0.05).. TPM decreases serum leptin and insulin levels in young and adult rats, especially in adult rats. VPA increases serum levels of both in young and adult rats, especially in young rats.

Topics: Age Factors; Animals; Anticonvulsants; Body Weight; Female; Fructose; Insulin; Leptin; Rats; Rats, Sprague-Dawley; Topiramate; Valproic Acid

Topics: Adolescent; Adult; Body Mass Index; Body Weight; Child; Child, Preschool; Cohort Studies; Female; Follow-Up Studies; Fructose; Humans; Infant; Infant, Newborn; Male; Middle Aged; Obesity; Time; Topiramate; Weight Loss

In recent years topiramate has been used for psychiatric patients, mainly for controlling substance use and food intake. A total of 46 patients who received topiramate treatment during the study period were identified from a computer database. Nineteen had received topiramate for at least 1 month. Twelve patients received topiramate for anticraving effects (alcohol, n = 9; heroin/amphetamine, n = 1; meperidine, n = 1; and nicotine, n = 1). On an average dosage of 112.5 mg/day, nine of the 12 patients (excluding three alcoholic patients) achieved complete or partial remission from the substance use disorders. The present results show that six of the nine patients achieved full or partial remission from alcohol use disorder on a dosage of 100 mg/day. Topiramate was also used to control seven patients' bodyweight (mean bodyweight change, 1.53 kg). Four of them achieved bodyweight loss in the 1-month follow up, with an average change of 2.65 kg. Based on the present findings topiramate <100 mg/day may be effective in treating patient with alcohol use disorder, and that topiramate has not shown remarkable benefit of bodyweight loss.

Topics: Adult; Agoraphobia; Anti-Obesity Agents; Body Weight; Databases, Factual; Depressive Disorder, Major; Eating; Female; Fructose; GABA Antagonists; Humans; Male; Middle Aged; Retrospective Studies; Substance-Related Disorders; Topiramate; Treatment Outcome

To evaluate the effectiveness of lithium augmentation of topiramate on mood symptoms, binge eating behavior, and body weight in obese bipolar patients with binge eating disorder (BED) seeking weight management.. We conducted a naturalistic study of 12 consecutive outpatients with bipolar disorders, BED, and obesity who received lithium augmentation for mood instability during the course of topiramate-based pharmacotherapy for obesity and BED. Lithium was added to topiramate (mean dose 514 mg i.d.) and titrated to a mean dose of 1009 mg i.d. (mean plasma concentration 0.7 mmol/L). Treatment response was assessed by comparing changes in clinical severity scales for mood and eating disorders, weekly binge eating frequency, and weight for the 2 months before and the first 2 months during lithium treatment.. A statistically significant improvement in global severity of mood symptoms was observed after as compared to before lithium augmentation. Statistically insignificant reductions in weight and in binge frequency and severity were also observed after lithium addition.. Optimal weight loss treatment in obese patients with comorbid bipolar and BEDs may require stabilization of mood. The combination of lithium and topiramate may have a role in the management of this difficult-to-treat population.

Topics: Adult; Anti-Obesity Agents; Antimanic Agents; Bipolar Disorder; Body Mass Index; Body Weight; Bulimia Nervosa; Comorbidity; Drug Interactions; Female; Follow-Up Studies; Fructose; Humans; Lithium Chloride; Male; Middle Aged; Obesity; Severity of Illness Index; Statistics, Nonparametric; Surveys and Questionnaires; Topiramate

We have studied the in vivo and in vitro effects of Topiramate (TPM) in female Zucker diabetic fatty (ZDF) rats. After weight matching, drug treatment had a marked effect to lower fasting glucose levels of relatively normoglycemic animals as well as during an oral glucose tolerance test. The glucose clamp studies revealed a approximately 30% increased glucose disposal, increased hepatic glucose output (HGO) suppression from approximately 30 to 60%, and an increased free fatty acid suppression from 40 to 75%. Therefore, TPM treatment led to enhanced insulin sensitivity at the level of tissue glucose disposal (increased ISGDR), liver (increased inhibition of HGO), and adipose tissue (enhanced suppression of lipolysis). When soleus muscle strips of control or TPM-treated ZDF rats were studied ex vivo, insulin-stimulated glucose transport was not enhanced in the drug-treated animals. In contrast, when isolated adipocytes were studied ex vivo, a marked increase (+55%) in insulin-stimulated glucose transport was observed. In vitro treatment of muscle strips and rat adipocytes showed no effect on glucose transport in muscle with a 40% increase in insulin-stimulated adipocyte glucose transport. In conclusion, 1) TPM treatment leads to a decrease in plasma glucose and increased in vivo insulin sensitivity; 2) insulin sensitization was observed in adipocytes, but not muscle, when tissues were studied ex vivo or in vitro; and 3) TPM directly enhances insulin action in insulin-resistant adipose cells in vitro. Thus the in vivo effects of TPM treatment appear to be exerted through adipose tissue.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Anti-Obesity Agents; Blood Glucose; Body Weight; Deoxyglucose; Eating; Fatty Acids, Nonesterified; Female; Fructose; Glucose; Glucose Tolerance Test; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Liver; Muscle, Skeletal; Ovary; Rats; Rats, Zucker; Topiramate

Topiramate is an antiepileptic drug known to have effects on weight. In order to use this as a tool to treat eating disorders, it is useful to examine whether these effects can be predicted in certain patients.. To report the effects of topiramate, initiated for the treatment of epilepsy, on top of ongoing treatment, on eating patterns and weight of 17 patients with traumatic brain injury (TBI) with post-traumatic epilepsy and weight gain of various etiologies.. Patients were followed up according to their usual treatment plan. Topiramate was added on top of current and stable treatment. Dose was titrated based on the patients' neurological status. Patients were asked to report side effects. No other changes were made.. Of the 17 patients included, one patient dropped out. Six patients with binge eating disorder (BED) demonstrated the most pronounced effects, with marked attenuation of binges and normalizing body mass index. Less noticeable were the effects in patients with mood disorders. Topiramate was ineffective in patients whose overweight was a side effect of their medication. Side effects were rated as mild and included somnolence, paresthesias, mild cognitive disturbances and some gastrointestinal disturbances.. In this report of the actual effects of topiramate in a clinical setting on weight and eating habits of 17 patients with TBI and obesity of various etiologies, topiramate seemed to be a safe intervention. Topiramate appeared to be differentially effective, with particular effects on primary pathological eating patterns.

Topics: Adult; Anticonvulsants; Body Weight; Brain Injuries; Bulimia; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Feeding Behavior; Female; Fructose; Humans; Male; Middle Aged; Neuroprotective Agents; Obesity; Psychiatric Status Rating Scales; Psychotic Disorders; Topiramate

Topiramate is a new anti convulsant agent that acts on the voltage-activated sodium channels and on the glutamate and GABA receptors; it is furthermore able to reduce hunger and therefore contributes to loss of weight. The authors report the case of a patient suffering from binge eating disorder, who was unresponsive to several therapeutic plans but was successfully treated with topiramate.

Topics: Adult; Anti-Obesity Agents; Body Weight; Bulimia; Female; Follow-Up Studies; Fructose; Humans; Psychiatric Status Rating Scales; Time Factors; Topiramate; Treatment Outcome

When administered chronically to rats, drugs that are effective in bipolar disorder-lithium and the anticonvulsants, valproic acid and carbamazepine-have been shown to downregulate the expression of certain enzymes involved in brain arachidonic acid (AA) release and cyclooxygenase (COX)-mediated metabolism. Phase II clinical trials with the anticonvulsant topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] suggest that this drug may also be effective for bipolar disorder.. To see if topiramate has effects similar to those of the other three drugs, we administered topiramate to rats for 14 days at 20 mg/kg, p.o. twice daily.. Compared with p.o. vehicle, topiramate treatment did not significantly affect the brain activity or protein level of cytosolic phospholipase A2, secretory PLA2, or Ca2+-independent iPLA2. Additionally, brain protein levels of COX-1, COX-2, 5-lipoxygenase, and cytochrome P450 epoxygenase were unchanged.. These results suggest that topiramate does not modify expression of the enzymes involved in brain AA metabolism that have been shown to be targeted by lithium, valproic acid, or carbamazepine. If topiramate proves effective in bipolar disorder, it may not act by modulating brain AA metabolism. In view of the proven anticonvulsant effect of topiramate, our results also suggest that the AA cascade is not involved in the anti-seizure properties of the drug.

Topics: Administration, Oral; Animals; Arachidonic Acid; Blotting, Western; Body Weight; Brain; Fructose; Immunoenzyme Techniques; Leptin; Male; Phospholipases A; Phospholipases A2; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred F344; Time Factors; Topiramate

Topics: Adolescent; Anti-Obesity Agents; Antidepressive Agents, Second-Generation; Appetite; Body Weight; Bupropion; Caloric Restriction; Dose-Response Relationship, Drug; Drug Administration Schedule; Fructose; Humans; Male; Muscular Dystrophy, Duchenne; Obesity; Topiramate; Treatment Outcome

Topiramate, an antiepileptic drug with a number of mechanisms of action including blockade of AMPA/KA receptor subtypes, was assessed as a neuroprotective agent following seizures. We administered topiramate or saline chronically during and following a series of 25 neonatal seizures. After completion of the topiramate treatment, animals were tested in the water maze for spatial learning and the open field for activity level. Brains were then examined for cell loss and sprouting of mossy fibers. Rats treated with topiramate performed significantly better in the water maze than rats treated with saline. Topiramate treatment also reduced the amount of seizure-induced sprouting in the supragranular region. There were no differences between topiramate- and saline-treated rats in activity level in the open field, swimming speed, or weight gain. These findings show that long-term treatment with topiramate after neonatal seizures changes the long-term consequences of seizures and improves cognitive function.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Anticonvulsants; Body Weight; Cognition; Drug Interactions; Exploratory Behavior; Flurothyl; Fructose; Hippocampus; Maze Learning; Motor Activity; Rats; Rats, Sprague-Dawley; Reaction Time; Seizures; Topiramate

Topics: Anticonvulsants; Body Weight; Epilepsy; Female; Fructose; Humans; Infant; Male; Topiramate

The first step in a study of possible cognitive side effects of topiramate in immature rats is to determine if and how topiramate (TPM) influences motor ability and spontaneous behavior. We therefore studied the effects of TPM on motor performance of 12- and 25-day-old rats using age-appropriate tests. Spontaneous behavior in the open field was studied in 25-day-old animals only. TPM was administered intraperitoneally at 80 and/or 160 mg/kg; control rats were injected with solvent (dimethylsulfoxide). A battery of motor tests was conducted before and 1, 3, and 24 hours after administration; behavior in the open field was recorded 2 and 24 hours after TPM administration. The effects of TPM on motor performance were similar to those of solvent. A few differences were found only at the 3-hour interval in 12-day-old rats. Behavior in the open field was not impaired by TPM; on the contrary, an apparent anxiolytic effect was observed. Habituation (a decrease in locomotor activity during the 5-minute observation period), a form of simple nonassociative learning, was also not compromised by TPM. A single high dose of TPM resulted only in transient changes in motor performance. A possible anxiolytic effect observed in 25-day-old rats should be studied.

Topics: Age Factors; Animals; Animals, Newborn; Anticonvulsants; Behavior, Animal; Body Weight; Dose-Response Relationship, Drug; Exploratory Behavior; Fructose; Motor Activity; Psychomotor Performance; Rats; Rats, Wistar; Rotarod Performance Test; Topiramate

Patients treated with atypical antipsychotic drugs commonly gain excess weight. Because obesity is associated with considerable morbidity and decreased life expectancy, treatment of weight gain in these patients is critical. Topiramate, a fairly new anticonvulsant, promotes bodyweight loss in healthy obese subjects, patients with bipolar disorder, and patients with eating disorder. However, there are very few reports about the efficacy of topiramate for weight management in schizophrenic patients. We present the cases of three Taiwanese patients with schizophrenia whose bodyweight increased as a result of atypical antipsychotics treatment, then was controlled by topiramate without aggravation of their psychotic symptoms.

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Child, Preschool; Clozapine; Dibenzothiazepines; Female; Fructose; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Taiwan; Topiramate; Weight Gain

The objective of the present study was to investigate the effects of the antiepileptic drug topiramate (TPM) on components of energy balance in lean and obese (ob/ob) mice in the presence or absence of leptin. Lean and ob/ob mice infused with either leptin or phosphate-buffered saline were treated with TPM for 7 days. TPM was mixed into the diet and administered at a dose of 60 mg/kg/day, whereas leptin was infused at the rate of 100 microg/kg/day using osmotic minipumps, which were subcutaneously implanted in the interscapular region. Food intake and body weight were monitored throughout the study. Body composition was measured prior to and following treatment with TPM and leptin, using dual-energy X-ray absorptiometry (DEXA). Glucose (glucose oxidase method) and insulin (radioimmunoassay) were also determined. TPM and leptin significantly reduced body weight gain, food intake and body fat gain in obese mice. The effects of TPM and leptin on fat gain were also statistically significant in lean animals. There was no interaction of TPM and leptin on the energy balance variables, the effects of the two substances being additive instead. Leptin abrogated hyperinsulinemia in obese mutants whereas TPM did not alter insulin levels in either lean or obese mice. The combination of leptin and TPM led to the normalization of glucose levels in obese mice. Our study demonstrates an effect of TPM in leptin-deficient animals, which suggests that TPM does not require the presence of leptin to exert its effect. They also show that the effects of leptin and TPM can be additive. The treatment with leptin in ob/ob mice neither accentuated nor blunted the effect of TPM on energy balance.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Anticonvulsants; Appetite Regulation; Body Composition; Body Weight; Drug Interactions; Drug Synergism; Energy Metabolism; Female; Fructose; Infusion Pumps, Implantable; Insulin; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Topiramate

To assess the effect of topiramate (TPM) on body mass index (BMI) in paediatric epilepsy patients and to examine predictors of weight loss.. Retrospective, observational study.. University clinic epilepsy outpatient department.. Patients below age 18 years who received TPM for at least 12 months.. Changes in BMI (kg/m2) standard deviation scores (S.D.S.) from baseline to the follow-up periods of 12, 24 and 36 months were evaluated. The repeated measures t-test for paired samples, revealed significant decreases for BMI S.D.S. at 12 months (P = 0.004; n = 53) and 24 months (P = 0.044; n = 35), but no significant decrease at 36 months (n = 21). Analysis of variance revealed a predictor value of sex for BMI S.D.S. at 12 months (females more likely to lose weight; P = 0.037) and a predictor value of baseline BMI for BMI S.D.S. at 24 months (patients with a higher baseline BMI were more likely to lose weight; P = 0.047).. Weight loss is common in paediatric epilepsy patients who receive TPM and is sustained for at least one year. The pattern of weight loss differs according to sex and baseline BMI.

Topics: Adolescent; Analysis of Variance; Anticonvulsants; Body Mass Index; Body Weight; Child; Child, Preschool; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Male; Retrospective Studies; Sex Factors; Time Factors; Topiramate

A case control study was conducted to assess the effects of long-term ingestion of Topiramate on fertility, body and reproductive organ weight and level of sex hormones in Sprague-Dawley male rats.. Ten adult male rats were exposed to Topiramate diets at a concentration of 100 mg /kg for 60 days. Another ten control male rats received vehicle (distilled water). After 24 hours of the last dose, animals were autopsied under light anesthesia. Several parameters including, body and reproductive organ weight, sperm count and motility, serum testosterone, FSH, levels of cholesterol, triglyceride, SGOT and SGPT were all measured. Assessment of pregnancies in females mixed with tested males was also measured. The results of histological, histometrical and biochemical profiles were compared to that of the control group, and the significance of these results was measured using student's ''t'' and Chi- square tests.. Long-term ingestion of Topiramate for 60 days caused a significant decrease in spermatogenesis in seminiferous tubules of the testes. Sperm motility and density were also significantly reduced in cauda epididymides and testes of the treated group. The body weights and weight of reproductive organs (testes, epididymides, ventral prostate and seminal vesicle) were decreased considerably. Hormonal assay also showed significant decrease in testosterone levels. Testicular cell population dynamics also demonstrated a decrease in the number of both primary and secondary spermatocytes and spermatids in the treatment group. The number of female rats impregnated by male rats on long-term Topiramate diet had decreased. The number of implantations and the number of viable fetuses were also notably decreased in female rats impregnated by male rats ingested Topiramate. Histometry of reproductive organs confirmed these results.. these results confirm that the long-term Topiramate ingestion produces adverse effects on fertility and reproductive system in adult male rat.

Topics: Administration, Oral; Animals; Anticonvulsants; Aspartate Aminotransferases; Body Weight; Drug Administration Schedule; Female; Fertility; Fructose; Male; Organ Size; Prostate; Rats; Rats, Wistar; Sperm Motility; Spermatogenesis; Testis; Topiramate

Topiramate, an antiepileptic drug with a number of mechanisms of action including inhibition of glutamate activity at the AMPA and KA receptors, was assessed as a neuroprotective agent following seizures. We administered topiramate, 80 mg/kg, or saline for 4 weeks following a series of 25 neonatal seizures or status epilepticus (SE) induced by lithium-pilocarpine in postnatal day 20 rats. Age-matched control rats without a history of seizures were administered topiramate or saline. Following completion of the topiramate injections, animals were tested in the water maze for spatial learning and the brains examined for cell loss and sprouting of mossy fibers. While there was a trend for improved visual-spatial performance in the water maze following topiramate therapy in rats with neonatal seizures, no differences were found in the histological examination of the hippocampus. Neonatal rats exposed to 4 weeks of topiramate did not differ from non-treated controls in water maze performance or histological examination. In weanling rats subjected to SE, topiramate provided a moderate degree of neuroprotection, with topiramate-treated rats performing better in the water maze than rats receiving saline. However, no differences in cell loss or mossy fiber sprouting were found in the histological examination of the brains. These findings demonstrate that chronic treatment with topiramate following SE improves cognitive function. In addition, long-term administration of high-dose topiramate in the normal developing rat brain does not appear to impair cognitive performance.

Topics: Animals; Animals, Newborn; Anticonvulsants; Body Weight; Cell Death; Cognition; Convulsants; Disease Models, Animal; Epilepsy; Flurothyl; Fructose; Hippocampus; Lithium; Maze Learning; Mossy Fibers, Hippocampal; Muscarinic Agonists; Nerve Degeneration; Pilocarpine; Rats; Rats, Sprague-Dawley; Reaction Time; Recurrence; Research Design; Topiramate

Subsets of psychiatric patients gain excess body weight while receiving mood-stabilizing agents such as lithium carbonate or valproate sodium. Patients who gain excess weight may discontinue therapy, with severe consequences. Among the newer anticonvulsant agents, topiramate is a candidate agent for bipolar disorder and is associated with weight loss when used as adjunctive treatment.. This open-label, nonrandomized, chart-review study assessed changes in body weight and body mass index (BMI) in patients receiving topiramate, lithium, or valproate.. Data were extracted from the medical charts of patients admitted in 1999 and 2000 to a state psychiatric hospital with either schizophrenia, schizoaffective disorder, bipolar disorder, or other psychiatric diagnoses who were prescribed valproate, lithium, or topiramate and were reviewed for changes in body weight and BMI. The use of concomitant psychotropic medicines was recorded (eg, antipsychotic agents, antidepressant agents, other mood stabilizers such as gabapentin or carbamazepine). Continuous variables were analyzed using a factorial analysis of variance and the Student t test. Contingency statistics were used to analyze categorical variables.. A total of 214 patients were included in the chart review (123 men, 91 women; mean age, 39.4 years). Significantly more women than men received topiramate (P = 0.004). Patients receiving either lithium or valproate gained a mean (SD) of 6.3 (9.0) kg and 6.4 (9.0) kg, respectively, whereas patients receiving topiramate lost a mean 1.2 (6.3) kg (F = 11.54, df = 2,198; P < 0.001). Lithium- or valproate-treated patients experienced an increase in BMI (mean, 2.1 [3.0] for both groups), whereas topiramate-treated patients experienced a reduction in BMI (mean, -0.5 [2.4]); this result was statistically significant (F = 11.40, df = 2,198; P < 0.001). Finally, lithium- or valproate-treated patients gained >8% of their baseline body weight (8.2% [11.5%] for lithium-treated patients and 8.5% [11.9%] for valproate-treated patients), whereas topiramate-treated patients lost 0.7% (7.2%) of their body weight (F = 9.93, df= 2,198; P < 0.001).. Controlled studies for the efficacy of topiramate therapy in various psychiatric conditions are awaited. These data indicate that patients receiving topiramate experience body weight loss and a reduction in BMI. This advantage of topiramate may promote long-term adherence to treatment among psychiatric patients and possibly decrease the medical risks associated with obesity.

Topics: Adult; Anticonvulsants; Antimanic Agents; Body Mass Index; Body Weight; Data Collection; Female; Fructose; Humans; Lithium; Male; Medical Records; Psychotic Disorders; Topiramate; Valproic Acid

Topiramate is a new antiepileptic drug (AED) approved as add-on therapy. Previous studies have shown that topiramate has only a limited effect on other AEDs, but its own metabolism can be induced by enzyme-inducing drugs. The aim of this study was to investigate the influence of topiramate dose, age, and comedication, especially of carbamazepine, phenytoin, phenobarbital, oxcarbazepine, lamotrigine, and valproic acid (VPA) on topiramate serum concentrations in patients with epilepsy. In total, 480 samples of 344 inpatients who fulfilled the inclusion criteria (e.g., trough concentration, body weight available) were investigated. The topiramate serum concentration in relation to topiramate dose per body weight (level-to-dose ratio) was calculated and compared for patients receiving topiramate monotherapy and for patients receiving topiramate plus one other AED. Analysis of covariance (using age as covariate) showed that comedication had a highly significant influence on the topiramate serum concentrations. Regression analysis including all 480 samples confirmed that in combinations with phenytoin, carbamazepine, phenobarbital, and oxcarbazepine, the topiramate concentrations were significantly lower compared with topiramate monotherapy, whereas VPA and lamotrigine had no significant influence. Moreover, regression analysis indicated that primidone and methsuximide lowered topiramate concentrations, whereas gabapentin, bromide, and sulthiame did not. In addition to comedication, the patient's age was significantly correlated with topiramate clearance. In accordance with the results of previous studies, these results indicated that infants and children had lower topiramate concentrations than adults receiving the same topiramate dose per body weight. Comedication and age should be considered in adjusting topiramate dosage. Determination of topiramate serum concentrations may be useful, especially when enzyme-inducing drugs are withdrawn or added.

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Body Weight; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Infant; Infant, Newborn; Male; Middle Aged; Regression Analysis; Topiramate

Topiramate, a novel anticonvulsant, has shown promise in preliminary open trials in bipolar disorder, but there are no studies in primary depression. Topiramate's tendency to cause weight loss could be advantageous for many patients with mood disorders.. A chart review was conducted on 16 female outpatients with a primary major depressive episode and mild to moderate obesity who received open-label adjunctive topiramate. Ongoing psychotropics were continued at previous doses. Self-report symptoms were assessed before and after acute phase (4-8 weeks) treatment in a subset of 11 patients, and clinician ratings were assessed at all visits during extended phase (up to 40 weeks) treatment for the entire group.. Patient and clinician symptom ratings dropped significantly during acute phase treatment (5.5+/-1.2 weeks), but only 36% of patients were judged responders. At extended phase endpoint (17.7+/-13.4 weeks), 44% of patients were responders. Body mass index decreased significantly on topiramate, reflecting a mean weight loss of 6.1+/-8.2% from baseline. Central nervous system side effects were prominent.. Topiramate may have potential for the adjunctive treatment of depression in obese patients, but close monitoring of weight and adverse effects is warranted.

Topics: Adult; Antidepressive Agents; Body Weight; Depressive Disorder, Major; Female; Fructose; Humans; Obesity; Retrospective Studies; Topiramate

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Weight; Female; Fructose; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia; Topiramate; Weight Gain

Topics: Adult; Antipsychotic Agents; Body Weight; Chronic Disease; Clozapine; Fructose; Humans; Male; Neuroprotective Agents; Obesity; Schizophrenia, Paranoid; Topiramate; Weight Loss

Topiramate is a newly developed anticonvulsant agent with possible mood-stabilizing properties. Little is known about the short- and long-term effects of topiramate monotherapy in bipolar disorder. We here present the case of a 60-year-old female bipolar patient who received topiramate alone as maintenance treatment after recovering from euphoric mania. During 7 months, she was free from new manic symptomatology and she was able to reduce her overweight by 16.5 kg. The patient who is known to have a strongly hyperthymic temperament described symptoms of fatigue and sedation and eventually discontinued topiramate monotherapy. When she presented again in our bipolar clinic, severe euphoric mania had developed. After hospitalization, she slowly responded to oral sodium valproate loading plus zotepine. Her weight increased again and so did her triglyceride serum levels. Topiramate treatment and discontinuation did not seem to affect cholesterol serum levels.

Topics: Adult; Affect; Bipolar Disorder; Body Weight; Female; Fructose; Humans; Lipids; Neuroprotective Agents; Topiramate