topiramate and Weight-Loss

Topics: Adolescent; Adult; Anti-Obesity Agents; Child; Child, Preschool; Female; Fructose; Humans; Male; Obesity, Morbid; Pediatric Obesity; Retrospective Studies; Topiramate; Weight Loss

Obesity is a common chronic disease in children and adolescents and its prevalence is increasing worldwide. The causes are multifactorial but involve biological predisposition towards a specific body-weight set point and defended adipose tissue mass converging with an obesogenic environment. Comprehensive treatment of paediatric obesity includes lifestyle modification therapy, anti-obesity medications (AOMs) and/or metabolic surgery. Lifestyle modification therapy used alone produces fairly modest weight loss for most youth with obesity. The emergence of new AOMs has changed the landscape of paediatric weight management, improving the outlook for youth with obesity. This Review briefly highlights obesity development pathways in youth and the role that pharmacotherapy can play in counteracting these pathophysiological forces. Here, results from adolescent AOM clinical trials published since 2020 are reviewed, including the safety, efficacy and tolerability of the newest treatments (glucagon-like peptide 1 receptor agonists and phentermine-topiramate). The importance of a comprehensive and chronic care model, including both lifestyle modification and ongoing pharmacotherapy, will be discussed in the context of maximizing long-term health outcomes. Finally, insight will be provided into the emerging pipeline of AOMs (for example, incretin receptor co-agonists and tri-agonists) and how future therapies might fundamentally change the prognosis for youth with obesity.

Topics: Adolescent; Anti-Obesity Agents; Child; Fructose; Humans; Pediatric Obesity; Topiramate; Weight Loss

Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology that primarily affects obese women of childbearing age. Symptoms include disabling headaches, visual disturbances, and intracranial noises (pulsatile tinnitus). Currently, no standardized treatment guidelines are available and the current management focuses on weight loss and acetazolamide use. There is an increasing body of evidence suggesting that the initial use of topiramate may be considered in IIH treatment. Acetazolamide is the recommended initial treatment for IIH, with topiramate often used as a second-line agent. Topiramate has multiple benefits to indicate it would pose effective in IIH management. Through varying mechanisms, it leads to weight loss and improves migraine headache control, the most common headache phenotype in IIH. Topiramate also inhibits the carbonic anhydrase enzyme like acetazolamide to reduce intracranial pressure and treat papilledema. The safety profile of topiramate is comparable or superior to acetazolamide. To date, there are limited studies comparing topiramate to acetazolamide or other treatment modalities in IIH. Based on its varying mechanisms of action, topiramate is a strong potential treatment agent for IIH, yet acetazolamide is often chosen first-line. However, the data supporting use of acetazolamide or topiramate is inefficient to designate one agent preferred over the other. There is a need for further studies assessing topiramate use in the treatment of IIH, and comparing topiramate use to other treatment modalities.

Topics: Acetazolamide; Female; Headache; Humans; Intracranial Hypertension; Intracranial Pressure; Pseudotumor Cerebri; Topiramate; Weight Loss

Modest weight loss (5%-10%) is clinically meaningful in patients with overweight or obesity. However, greater weight loss may be required to achieve improvements in or remission of certain weight-related complications. Therefore, this study reviewed the effect of large weight loss (≥10%). Most studies reporting large weight loss and relevant outcomes used bariatric surgery or lifestyle modifications.. Benefits of large weight loss were observed in patients with various overweight- or obesity-related complications, including improvements in comorbidities such as type 2 diabetes and hypertension. Improvements in glucose metabolism and cardiovascular risk factors were observed in patients who achieved large weight loss through lifestyle interventions or pharmacotherapy (phentermine/topiramate 15/92 mg once daily or subcutaneous semaglutide 2.4 mg once weekly). Other benefits associated with large weight loss included reduced cancer risk and improvements in knee osteoarthritis, sleep apnea, fertility-related end points, and health-related quality of life. While costly, bariatric surgery is currently the most cost-effective intervention, although most weight-management programs are deemed cost-effective.. Overall, large weight loss has a major beneficial impact on overweight- and obesity-related complications. Large weight loss should be the main treatment target when modest weight loss has had insufficient effects on obesity-related complications and for patients with severe obesity.

Topics: Anti-Obesity Agents; Diabetes Mellitus, Type 2; Humans; Obesity; Overweight; Phentermine; Quality of Life; Topiramate; Weight Loss

The global incidence of childhood obesity is increasing. Currently, there are only few established drugs for treating adolescent obesity. Randomized clinical trials (RCTs) comparing pharmacological interventions in children with obesity are scarce; therefore, we aimed to analyze the relative efficacy and adverse reactions of these drugs and compare the effects of each drug on body mass index (BMI).. This meta-analysis focused on the slimming effect, safety, and correlation of metformin, orlistat, exenatide, liraglutide, and topiramate in children with obesity. Several international databases were searched and clinical trials on the treatment of obesity in children in which the drug was administered for ≥ 6 months were included. Changes in BMI before and after treatment were analyzed using a Bayes framework, and the surface under the cumulative ranking was calculated.. Of 2102 relevant articles retrieved, 21 RCTs were included in the study. Compared to other drugs, liraglutide reduced BMI the most in children with obesity. However, it was most associated with drug withdrawal due to adverse events while topiramate was least.. Liraglutide had a higher probability of achieving clinically significant weight loss compared with other drugs while topiramate was superior in safety.

Topics: Adolescent; Anti-Obesity Agents; Child; Exenatide; Humans; Liraglutide; Metformin; Obesity; Orlistat; Topiramate; Weight Loss

Topics: Adolescent; Adult; Anti-Obesity Agents; Child; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Fructose; Humans; Non-alcoholic Fatty Liver Disease; Obesity; Phentermine; Sleep Apnea Syndromes; Sympathomimetics; Topiramate; Weight Loss

As a chronic and relapsing disease, obesity impairs metabolism and causes cardiovascular diseases. Although behavioral modification is important for the treatment of obesity, it is difficult to achieve an ideal weight or sustain the process of long-term weight loss. Therefore, the obesity control guidelines strongly recommend lifestyle interventions along with medical treatment for patients who are overweight. There is sufficient evidence supporting that pharmacotherapy in combination with behavior-based interventions can result in significant weight loss and improved cardiometabolism.. Recent meta-analyses of new anti-obesity drugs and their weight-loss efficacy have shown that the overall placebo-subtracted weight reduction (%) for at least 12 months ranged from 2.9 to 6.8% for the following drugs: phentermine/topiramate (6.8%), liraglutide (5.4%), naltrexone/bupropion (4.0%), orlistat (2.9%), and lorcaserin (3.1%). However, very recently, on February 13, 2020, the US Food and Drug Administration (FDA) ordered the withdrawal of lorcaserin from markets, as a clinical trial to assess drug safety showed an increased risk of cancer. Currently, the anti-obesity medications that have been approved by the FDA for chronic weight management are orlistat, phentermine/topiramate, naltrexone/bupropion, and liraglutide. However, they are costly and may have adverse effects in some individuals. Therefore, drug therapy should be initiated in obese individuals after weighing its benefits and risks. One of the strategies for long-term obesity control is that anti-obesity medications should be tailored for specific patients depending on their chronic conditions, comorbidities, and preferences.

Topics: Animals; Anti-Obesity Agents; Benzazepines; Bupropion; Humans; Liraglutide; Naltrexone; Obesity; Orlistat; Overweight; Phentermine; Topiramate; United States; United States Food and Drug Administration; Weight Loss

Weight regain after bariatric surgery is unfortunately a common occurrence. In this article, we have reviewed the data addressing this clinical problem focusing on pharmacological management of weight regain.. Data from several small, non-randomized, retrospective, and prospective studies provide evidence that a number of pharmacological options, both FDA approved and off-label, are effective in mitigating and managing weight regain after bariatric surgery. There is a suggestion that the optimal time to initiate weight loss medications may be at the time of weight plateau, rather than after weight regain. Adjuvant pharmacotherapy can help treat weight regain after bariatric surgery. Future studies should investigate the optimal timing for starting weight loss medications, as well as the best medication or combinations of medicines, for managing postoperative weight regain in different patient groups, including those who have undergone different types of bariatric surgeries.

Topics: Anti-Obesity Agents; Bariatric Surgery; Humans; Liraglutide; Obesity; Phentermine; Postoperative Period; Topiramate; Weight Gain; Weight Loss

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

Four new medicines-liraglutide, lorcaserin, bupropion/naltrexone, and phentermine/topiramate-have been recently added to the pharmacological arsenal for obesity treatment and could represent important tools to manage this epidemic disease. To achieve satisfactory anti-obesity goals, the use of these new medicines should be optimized and tailored to specific patient subpopulations also by applying dose adjustments if needed. In the present review, we posit that gender could be among the factors influencing the activity of the new obesity drugs both because of pharmacokinetic and pharmacodynamic factors. Although evidence from premarketing clinical studies suggested that no dose adjustment by gender is necessary for any of these new medicines, these studies were not specifically designed to identify gender-related differences. This observation, together with the strong theoretical background supporting the hypothesis of a gender-dimorphic response, strongly call upon an urgent need of new real-life data on gender-related difference in the pharmacology of these new obesity drugs.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Liraglutide; Male; Naltrexone; Obesity; Patient Selection; Sex Factors; Topiramate; Treatment Outcome; Weight Loss

This review provides an overview of the current state of drug therapy for obesity, with a focus on four new drug therapies-lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide 3.0 mg-which have been approved by the US Food and Drug Administration (FDA) for long-term management of obesity since 2012. Topics discussed in this paper include rationale for pharmacotherapy, history of antiobesity drugs, and efficacy and safety data from randomized controlled trials with implications for clinical practice.. Weight loss achieved by currently approved drugs ranges from approximately 3 to 9%, above and beyond weight loss with lifestyle counseling alone, after a year. Response and attrition rates in clinical trials indicate that the benefits of pharmacotherapy range from substantial for some patients, modest for others, and no benefits for others still. Decisions regarding selection of a suitable drug from the available pharmacotherapy options and duration of treatment should be based on the expected and observed benefit-to-risk balance and tailored to the needs of each individual patient using the principles of shared decision-making.

Topics: Anti-Obesity Agents; Benzazepines; Clinical Trials as Topic; Fructose; Humans; Life Style; Liraglutide; Obesity; Phentermine; Topiramate; Weight Loss

To review and compare the phase 3 clinical trial evidence on the 4 new pharmacological agents approved for the management of overweight and obesity.. Searches were performed (from 1966 through January 2016) in PubMed/MEDLINE, Scientific Citation Index, and product package inserts to identify key phase 3 clinical trials that were used in the approval of each agent.. Phase 3 clinical trials that listed end points of ≥5% and ≥10% weight loss benchmarks from baseline as well as total percentage of weight loss by participants were selected for the review.. No head-to-head trials have been identified between these agents at this point, which limits comparisons across agents. Phentermine/topiramate ER appeared to have the best overall average weight loss from baseline as well as highest percentages of patients achieving both ≥5% and ≥10% weight loss benchmarks, followed second by naltrexone/bupropion, and then liraglutide, with lorcaserin showing the lowest rates. Phentermine/topiramate ER completion rates were highest for both treatment and placebo groups, followed by liraglutide, with lorcaserin and naltrexone/bupropion showing similar completion rates, below that of the other 2 agents. Common side effects reported differed between agents, although the most common adverse events reported were gastrointestinal in nature, with liraglutide demonstrating the highest reported rates and lorcaserin demonstrating the lowest.. These 4 new pharmacological agents represent new options for the clinician to utilize when trying to manage the problem of obesity. No clear first-line agent has emerged, so treatment decisions should be based on patient-specific factors.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Clinical Trials, Phase III as Topic; Drug Combinations; Fructose; Humans; Liraglutide; Naltrexone; Obesity; Phentermine; Topiramate; Weight Loss

All major guidelines on antihypertensive therapy recommend weight loss; anti-obesity drugs may be able to help in this respect.. 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).. To assess the long-term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction.. We obtained studies using computerised searches of the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid EMBASE, the clinical trials registry ClinicalTrials.gov, and from handsearches in reference lists and systematic reviews (status as of 13 April 2015).. Randomised controlled trials in hypertensive adults of at least 24 weeks' duration that compared long-term pharmacologic interventions for weight loss with placebo. . Two review authors independently selected studies, assessed risk of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of heterogeneity.. After updating the literature search, which was extended to include four new weight-reducing drugs, we identified one additional study of phentermine/topiramate, bringing the total number of studies to nine that compare orlistat, sibutramine, or phentermine/topiramate to placebo and thus fulfil our inclusion criteria. We identified no relevant studies investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion. No study included mortality and cardiovascular morbidity as predefined outcomes. Incidence of gastrointestinal side effects was consistently higher in those participants treated with orlistat versus those treated with placebo. The most frequent side effects were dry mouth, constipation, and headache with sibutramine, and dry mouth and paresthaesia with phentermine/topiramate. In participants assigned to orlistat, sibutramine, or phentermine/topiramate body weight was reduced more effectively than in participants in the usual-care/placebo groups. Orlistat reduced systolic blood pressure as compared to placebo by -2.5 mm Hg (mean difference (MD); 95% confidence interval (CI): -4.0 to -0.9 mm Hg) and diastolic blood pressure by -1.9 mm Hg (MD; 95% CI: -3.0 to -0.9 mm Hg). Sibutramine increased diastolic blood pressure compared to placebo by +3.2 mm Hg (MD; 95% CI: +1.4 to +4.9 mm Hg). The one trial that investigated phentermine/topiramate suggested it lowered blood pressure.. In people with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree, while phentermine/topiramate reduced body weight to a greater extent. In the same trials, orlistat and phentermine/topiramate reduced blood pressure, while sibutramine increased it. We could include no trials investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion in people with elevated blood pressure. Long-term trials assessing the effect of orlistat, liraglutide, lorcaserin, phentermine/topiramate, or naltrexone/bupropion on mortality and morbidity are unavailable and needed. Rimonabant and sibutramine have been withdrawn from the market, after long-term trials on mortality and morbidity have confirmed concerns about the potential severe side effects of these two drugs. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while the application for European marketing authorisation for lorcaserin was withdrawn by the manufacturer after the Committee for Medicinal Products for Human Use judged the overall benefit/risk balance to be negative.

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

Binge eating disorder (BED) is characterized by recurrent binge eating and marked distress about binge eating without the extreme compensatory behaviors for weight control that characterize other eating disorders. BED is prevalent, associated strongly with obesity, and is associated with heightened levels of psychological, psychiatric, and medical concerns. This article provides an overview of randomized controlled treatments for combined psychological and pharmacological treatment of BED to inform current clinical practice and future treatment research. In contrast to the prevalence and significance of BED, to date, limited research has been performed on combining psychological and pharmacological treatments for BED to enhance outcomes. Our review here found that combining certain medications with cognitive behavioral therapy (CBT) or behavioral weight loss (BWL) interventions produces superior outcomes to pharmacotherapy only but does not substantially improve outcomes achieved with CBT/BWL only. One medication (orlistat) has improved weight losses with CBT/BWL albeit minimally, and only one medication (topiramate) has enhanced reductions achieved with CBT in both binge eating and weight. Implications for future research are discussed.

Topics: Anti-Obesity Agents; Binge-Eating Disorder; Bulimia Nervosa; Cognitive Behavioral Therapy; Fructose; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Topiramate; Weight Loss

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

Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited.. To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis.. MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries.. Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo.. Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria.. Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year.. Twenty-eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6 kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates.. Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.

Topics: Anti-Obesity Agents; Bayes Theorem; Benzazepines; Drug Combinations; Female; Fructose; Humans; Lactones; Liraglutide; Male; Middle Aged; Naltrexone; Obesity; Orlistat; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Weight Loss

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

In 2014 we have 4 new weight loss medications and one older medication with very different mechanisms of action – all approved for chronic weight management. Each medication has its own unique risk profile that makes patient selection important. Knowledge of the contraindications and safety issues can guide physicians to the most appropriate choice for a particular patient. Obesity medicine is entering a new era where our available options for prescribing have been very well studied. There should be no surprises, because bupropion, naltrexone, phentermine, topiramate and liraglutide have been prescribed for many years in millions of patients and lorcaserin has high specificity for a single receptor subtype. The FDA demanded very detailed risk-oriented studies to have these medications approved. In addition, the FDA has established REMS programs or risk management strategies to help ensure that the patients do not receive inappropriate medications. These medications were approved by the US FDA after very thorough testing. The decision to approve these medications was based on the benefits out-weighing the risks. Thus, if following the appropriate guidelines according to package labels, the practitioner can feel safe in prescribing these medications.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Delayed-Action Preparations; Drug-Related Side Effects and Adverse Reactions; Drugs, Investigational; Fructose; Glucagon-Like Peptide 1; Humans; Liraglutide; Naltrexone; Obesity; Phentermine; Topiramate; United States; United States Food and Drug Administration; Weight Loss

Losing ≥ 5% of initial weight improves quality of life and risk factors for cardiovascular disease (CVD) in obese individuals. Lifestyle modification, the cornerstone of weight reduction, may be complemented by pharmacotherapy. In 2012, the FDA approved the combination of phentermine and topiramate extended release (ER) for chronic weight management, as an adjunct to lifestyle modification.. This review examines the safety and efficacy of phentermine-topiramate ER, as determined by randomized controlled trials (RCTs). A preliminary study confirmed the benefit of combining the two medications for improving weight loss and reducing adverse effects, as compared to using equivalent-dose monotherapy alone.. Across RCTs, groups prescribed phentermine 15 mg/topiramate ER 92 mg lost an average of 10% of initial weight, ∼ 8% more than placebo and 2% more than phentermine 7.5 mg/topiramate 46 mg. Weight loss reduced the risk of developing type 2 diabetes and improved CVD risk factors. Phentermine-topiramate ER, however, was associated with increased heart rate, the clinical significance of which is being investigated in an FDA-required CVD outcomes study. The medication also must be used with caution in women of child-bearing age because of an increased risk to infants of oral cleft.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Disease Management; Drug Combinations; Fructose; Humans; Life Style; Obesity; Phentermine; Randomized Controlled Trials as Topic; Risk Factors; 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

Persistent headache and loss of visual acuity combined with papilledema are the predominant symptoms of idiopathic intracranial hypertension (IIH). The clinical signs are not different from those seen in other diseases with elevated intracranial pressure. To differentiate primary and secondary forms of increased intracranial pressure neuroimaging procedures and analysis of cerebrospinal fluid (CSF) are absolutely essential according to national and international guidelines. Lumbar puncture reveals an elevated opening pressure in cases of IIH as the only pathological finding. Treatment options are serial lumbar punctures combined with body weight reduction as well as medication with carbonic anhydrase inhibitors, such as acetazolamide and topiramate or diuretic therapy with furosemide. In some patients surgical options, e.g. optic nerve sheath fenestration, CSF shunting procedures including ventriculoperitoneal and lumboperitoneal shunt systems and bariatric surgery also have to be considered. In recent years modern neuroradiological procedures have also been applied (e.g. venous stenting in cases of sinus obstruction) in some centers.

Topics: Acetazolamide; Cerebrospinal Fluid Shunts; Combined Modality Therapy; Diagnosis, Differential; Fructose; Furosemide; Guideline Adherence; Headache Disorders; Neurologic Examination; Pseudotumor Cerebri; Spinal Puncture; Topiramate; Vision Disorders; Visual Acuity; Weight Loss

The binge eating disorder is a relatively new type of eating disorders, which was first described in 1992, and became a distinct nosological entity in the system of DSM-5 in 2013. Its central symptom is the binge, which is not followed by compensatory behaviours as in bulimia nervosa. Therefore, the patients are generally obese. The prevalence of the disorder is 1-3% in the general population, but much higher in help-seeking obese subjects. The two main goals of the therapy is body weight reduction, and the cessation of binges. In the pharmacotherapy of binge eating disorder the antidepressants are recommended mainly in the case of unsuccessful psychotherapy, and in treating comorbid depression. In the field of psychotherapy data are available mainly on the effectiveness of cognitive behavioural therapy, dialectic behaviour therapy, behavioural weight loss, and interpersonal therapy. Effectivity studies on new therapeutic methods and treatment combinations are needed as well as long term follow-up studies.

Topics: Anti-Obesity Agents; Antidepressive Agents; Binge-Eating Disorder; Bulimia; Cognitive Behavioral Therapy; Diagnostic and Statistical Manual of Mental Disorders; Directive Counseling; Fructose; Humans; Internet; Meta-Analysis as Topic; Prevalence; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Self-Help Groups; Severity of Illness Index; Topiramate; Weight Gain; Weight Loss

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.

Topics: Anti-Obesity Agents; Bariatric Surgery; Benzazepines; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Exercise; Feeding Behavior; Female; Fructose; Glucagon-Like Peptide-1 Receptor; Glucosides; Glycated Hemoglobin; Homeostasis; Humans; Islet Amyloid Polypeptide; Lactones; Male; Minimally Invasive Surgical Procedures; Obesity, Morbid; Orlistat; Phentermine; Receptors, Glucagon; Topiramate; Treatment Outcome; Weight Loss

Weight loss can reduce the increased cardiovascular risk associated with obesity. Pharmacotherapy is a recognized weight loss treatment option; however, cardiovascular safety issues with some previous weight loss drugs raise concerns for newly approved pharmacotherapies. Phentermine is approved for short-term obesity treatment in conjunction with lifestyle modifications, but is commonly used chronically. Topiramate, approved for treating epilepsy and preventing migraines, also induces weight loss. A single-dose combination of low-dose phentermine and topiramate extended-release was recently approved by the United States Food and Drug Administration as an adjunct to lifestyle intervention for the chronic treatment of overweight/obese adults. This review summarizes and evaluates the cardiovascular risk/benefit profile associated with phentermine and topiramate, individually and in combination. Cardiovascular data associated with long-term use of phentermine and topiramate extended-release indicate that this combination may be a safe and effective option for reducing weight in overweight/obese patients at low-to-intermediate cardiovascular risk.

Topics: Aged; Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Comorbidity; Drug Combinations; Female; Fructose; Humans; Male; Middle Aged; Obesity; Overweight; Phentermine; Randomized Controlled Trials as Topic; Risk Factors; Topiramate; Treatment Outcome; Weight Loss

The treatment of obesity is often met with a myriad of challenges in the primary care setting. Nevertheless, a modest 5% weight loss is considered clinically significant and may be associated with health benefits. Phentermine/topiramate (Qsymia), available in the United States since September 2012, achieves clinically meaningful weight loss along with improvements in weight-related comorbidities. This combination drug therapy could be an additional tool for primary care providers in their quest for effective management of obesity. Special precautions and close monitoring are indicated when prescribing phentermine/topiramate for women of childbearing potential. Monitoring of heart rate and psychiatric and cognitive side effects is important.

Topics: Anti-Obesity Agents; Clinical Trials, Phase III as Topic; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Fructose; Humans; Obesity; Phentermine; Primary Health Care; Topiramate; Treatment Outcome; United States; Weight Loss

A short overview of new drugs approved for the treatment of obesity (lorcaserin, phentermine/topiramate combination) as well as those with a perspective for approval as antiobesity drugs (cetilistat, naltrexone/bupropion combination, liraglutide) is presented. All these drugs produce significant weight loss accompanied by reductions in cardiometabolic health risks. Although the adverse events were rather rare and tended to decrease with the duration of treatment with most of these medications, the drug-specific safety concerns should be seriously considered. In order to ensure an appropriate, efficient and safe implementation of novel antiobesity drugs into the comprehensive treatment of obesity, it will be necessary to establish a network of physicians and other health-care providers well educated in obesity management.

Topics: Anti-Obesity Agents; Benzazepines; Benzoxazines; Bupropion; Drug Combinations; Fructose; Glucagon-Like Peptide 1; Humans; Liraglutide; Naltrexone; Obesity; Phentermine; Topiramate; Weight Loss

Medications for the treatment of obesity began to appear in the late 19th and early 20th century. Amphetamine-addiction led to the search for similar drugs without addictive properties. Four sympathomimetic drugs currently approved in the US arose from this search, but may not be approved elsewhere. When noradrenergic drugs were combined with serotonergic drugs, additional weight loss was induced. At present there are three drugs (orlistat, phentermine/topiramate and lorcaserin) approved for long-term use and four sympathomimetic drugs approved by the US FDA for short-term treatment of obesity. Leptin produced in fat cells and glucagon-like peptide-1, a gastrointestinal hormone, provide a new molecular basis for treatment of obesity. New classes of agents acting on the melanocortin system in the brain or mimicking GLP-1 have been tried with variable success. Combination therapy can substantially increase weight loss; a promising approach for the future.

Topics: Anti-Obesity Agents; Benzazepines; Drug Therapy, Combination; Fructose; Humans; Lactones; Obesity; Orlistat; Phentermine; Topiramate; Weight Loss

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Body Mass Index; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Evidence-Based Medicine; Female; Fructose; Humans; Male; Middle Aged; Obesity; Overweight; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; United States; Weight Loss; Young Adult

Obesity is a major public health concern associated with increased morbidity and mortality. Its prevalence is rising worldwide mainly due to modern lifestyle habits. Several mechanisms like inflammation, endothelial dysfunction, increased sympathetic tone, high leptin and insulin concentrations as well as enhanced thrombogenesis are implicated to the emergence and progress of cardiovascular disease. Although, changes in the lifestyle remain the cornerstone of antiobesity treatment, alone do not always provide the desired weight loss. Often, the addition of pharmacotherapy or bariatric surgery is considered the treating option for patients meeting eligibility criteria. Although, bariatric surgery is limited to patients with a high body mass index due to the risks of the procedures, the effects of anti-obesity medication on cardiovascular outcome are still unclear. Several anti-obesity drugs have been abandoned because of serious adverse events. Qsymia is a combination of phentermine and topiramate used for obesity treatment. Administration of this drug reduces body weight and has favorable effects in various metabolic and anthropometric parameters. However, there are concerns regarding cardiovascular safety of this drug. In this review, we are going to present the history of current antiobesity medication focusing on the combination of phentermine and topiramate and recent patents.

Topics: Animals; Anti-Obesity Agents; Cardiovascular Diseases; Delayed-Action Preparations; Drug Combinations; Fructose; Humans; Obesity; Patents as Topic; Phentermine; Topiramate; Treatment Outcome; Weight Loss

Weight-management options include lifestyle modifications, bariatric surgery and, until recently, limited pharmacotherapy. Phentermine and topiramate extended-release (phentermine/topiramate ER) has recently been approved in the USA for chronic weight management in obese adults and overweight adults with weight-related co-morbidities in conjunction with a reduced-calorie diet and increased physical activity.. This review describes the pharmacology and clinical trials data for phentermine/topiramate ER and its role in a complications-centric approach to medical care of the overweight and obese patient.. Phentermine/topiramate ER is an effective and safe weight-loss medication that can produce and sustain approximately 10% loss of body weight. This is a landmark development in the pharmacotherapy of obesity. By offering an effective medical option to complement lifestyle and surgical approaches, phentermine/topiramate ER enables a comprehensive medical model for obesity care. The overall approach to the overweight and obese patient should be to identify individuals who will benefit most from therapy based on cardiometabolic or mechanical complications, establish therapeutic targets and goals for ameliorating these complications and selecting the treatment modality and intensity for weight loss to achieve these goals. This complications-centric model emphasizes weight loss as a tool to ameliorate obesity-related complications and optimizes benefit/risk for achieving the best outcomes in overweight/obese patients.

Topics: Anti-Obesity Agents; Delayed-Action Preparations; Fructose; Humans; Obesity; Overweight; Phentermine; Topiramate; Weight Loss

Obesity is an epidemic associated with significant morbidity. Lorcaserin , a novel serotonin 2C receptor antagonist, was recently approved as an adjunct to lifestyle modification for long-term weight loss and maintenance. Clinical studies in patients without diabetes demonstrated 5.8% mean weight loss from baseline with lorcaserin compared to 2.5% with placebo and over twice as many patients achieved ≥ 5% weight loss. Patients with diabetes achieved mean weight loss of 4.5% with lorcaserin compared to 1.5% with placebo as well as modest improvements in glycemic outcomes.. The authors review the pharmacology and clinical efficacy as well as the safety and tolerability of lorcaserin. This was achieved through a PubMed search (1960 - present) on lorcaserin to generate the key literature in the area. The lorcaserin package insert and Food and Drug Administration briefing documents were also used to identify relevant information. To assess long-term clinical efficacy and safety, the authors used studies with a minimum duration of one year.. Lorcaserin induces moderate but significant weight loss compared to placebo as an adjunct to lifestyle modification. Although head-to-head comparison trials are not available, lorcaserin is likely less effective but better tolerated than its recently approved competitor, phentermine/topiramate. Cardiovascular outcome data will be invaluable in determining lorcaserin's eventual utilization and place in therapy.

Topics: Benzazepines; Clinical Trials, Phase III as Topic; Drug Interactions; Fructose; Humans; Obesity; Randomized Controlled Trials as Topic; Receptor, Serotonin, 5-HT2C; 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

Although serious health concerns are associated with obesity, losing even 5% of body weight can produce clinically relevant effects. The initial goal of obesity management is usually a 5% to 10% weight reduction. Some people will sustain weight loss with changes in diet and exercise alone; however, these patients represent the minority, and a large percentage are unable to maintain weight loss over time. Patients and providers often wish to intensify obesity treatment, and therefore interest in new medications has been considerable. Until recently, only two antiobesity medications have received Food and Drug Administration approval for long-term use. In June and July of 2012, respectively, lorcaserin and combination phentermine/topiramate extended-release were approved for obesity therapy. The first section of this article reviews mechanisms, clinical trials, benefits and risks of available medications for treating obesity. Bariatric surgery is the next step for patients with a body mass index of ≥40 kg/m(2) or ≥35 kg/m(2) with comorbidities, based on National Institutes of Health Clinical Guidelines. These procedures and their risks and benefits are reviewed in the second section. The final section presents common clinical scenarios with guidance for choosing among evidence-based recommendations for developing optimal, individualized, long-term strategies for patients with obesity.

Topics: Anti-Obesity Agents; Bariatric Surgery; Clinical Trials as Topic; Diet, Reducing; Drug Therapy, Combination; Evidence-Based Practice; Exercise; Female; Fructose; Humans; Male; Obesity; Phentermine; Topiramate; Weight Loss

Drug-induced weight alteration can be a serious side effect that applies to several therapeutic agents and must be referred to in the respective approved labeling texts. The side effect may become health threatening in case of significant weight change in either direction. Several antiepileptic drugs (AEDs) are associated with weight gain such as gabapentin, pregabalin, valproic acid, and vigabatrin and to some extent carbamazepine. Others are weight neutral such as lamotrigine, levetiracetam, and phenytoin or associated with slight weight loss as, e.g., felbamate. The focus of this chapter is on the two AEDs causing strong weight loss: topiramate and zonisamide. For both drugs, several molecular mechanisms of actions are published. We provide a review of these potential mechanisms, some of which are based on in vivo studies in animal models for obesity, and of clinical studies exploring these two drugs as single entities or in combinations with other agents.

Topics: Animals; Anticonvulsants; Drug Therapy, Combination; Fructose; Humans; Isoxazoles; Risk Assessment; Risk Factors; Topiramate; Weight Loss; Zonisamide

The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials.

Topics: Anti-Obesity Agents; Benzazepines; Benzoxazines; Bupropion; Clinical Trials as Topic; Drug Combinations; Fructose; Glucagon-Like Peptide 1; Humans; Lactones; Life Style; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate; Weight Loss

Topiramate was associated with weight loss in clinical trials. We summarize the evidence on the efficacy and safety of topiramate in the treatment of overweight/obesity. The databases Medline, Embase, and Cochrane were searched. Randomized controlled studies with at least 16 weeks of duration that report the effect of topiramate on weight loss and adverse events were eligible for inclusion. Ten studies were included (3320 individuals). Patients treated with topiramate lost an average of 5.34 kg (95% confidence interval [95%CI]-6.12 to -4.56) of additional weight as compared with placebo. According to meta-regression analysis, treatment duration and dosage were associated with the efficacy of topiramate treatment. Evaluating trials using topiramate 96-200 mg day(-1) , the weight loss was higher in trials with >28 weeks of duration (-6.58 kg [95%CI -7.48 to -5.68]) than in trials with ≤28 weeks (-4.11 kg [95%CI -4.92 to -3.30]). Data of 6620 individuals were available for adverse events evaluation and those more frequently observed were paraesthesia, taste impairment and psychomotor disturbances. The odds ratio for adverse events leading to topiramate withdrawal was 1.94 (95%CI 1.64-2.29) compared with the control group. In conclusion, topiramate might be a useful adjunctive therapeutic tool in the treatment of obesity as long as proper warnings about side effects are considered.

Topics: Anti-Obesity Agents; Fructose; Humans; Obesity; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; Weight Loss

Weight loss can occur during topiramate (TPM) treatment and it should be evaluated by clinicians, especially in children, whose growth could be compromised. In international literature, the reported body weight loss incidences linked to TPM therapy vary widely and, in some cases, are very conflicting.. The aims of this review are to quantify TPM-induced weight loss, analyze the pathogenetic mechanisms and evaluate its clinical implications in patients with epilepsy.. The amount of weight loss appears to be related to some factors such as the duration of the treatment and a high baseline body mass index (BMI), while the role of daily dosage and gender of patients is controversial. The mechanism through which TPM may induce weight loss is still unclear.. TPM is able to induce weight loss, especially in high baseline BMI patients, not strictly depending on daily dosage and perhaps not influenced by gender. This makes TPM a good choice, especially in obese patients suffering from seizures. However, TPM can make nutritionally vulnerable children or adult patients, with epilepsy associated with other neuropsychiatric diseases, who cannot voluntarily increase their caloric intake.

Topics: Anti-Obesity Agents; Databases, Factual; Energy Metabolism; Epilepsy; Fructose; Hormones; Humans; Obesity; Sex Factors; Topiramate; Weight Loss

To compare antipsychotic and mood stabilizer (MS) efficacy and tolerability in youth and adults with bipolar mania.. Medline/PubMed search for studies including: (i) youth (< 18 years) or adults (> or = 18 years); (ii) bipolar I disorder; (iii) double-blind, randomized, placebo-controlled trial (DB-RPCT); (iv) < or = 12 weeks of treatment; and (v) calculable effect sizes (ES) and/or numbers needed to treat/harm (NNT/NNH) +/- 95% confidence intervals (CI). Non-overlapping 95% CIs determined significant group differences.. We identified nine DB-RPCTs in youth (n = 1,609), 5 evaluating second-generation antipsychotics (SGAs) (n = 1,140) and 4 evaluating MSs (n = 469). We also identified 23 DB-RPCTs in adults (n = 6,501), 14 including SGAs (n = 3,297), 5 using haloperidol as an active comparator (n = 580), and 11 including MSs (n = 2,581). Young Mania Rating Scale scores improved significantly more with SGAs than MSs in youth (ES = 0.65, CI: 0.53-0.78 versus 0.24, CI: 0.06-0.41) and adults (ES = 0.48, CI: 0.41-0.55 versus 0.24, CI: 0.17-0.31). After excluding topiramate studies, SGAs had larger ES than MSs only in youth (ES = 0.65, CI: 0.53-0.78 versus 0.20, CI: 0.02-0.39), but not adults (ES = 0.48, CI: 0.41-0.55 versus 0.46, CI: 0.37-0.55). However, in adults SGAs had significantly larger ES regarding Clinical Global Impressions scores than MSs, even without topiramate (ES = 0.75, CI: 0.68-0.82 versus 0.24, CI: 0.07-0.41). Rates of response, remission, and discontinuation due to any reason compared to placebo were similar between medication and age groups, except for more favorable NNTs for remission with SGAs than MSs in adults after excluding topiramate. SGAs caused more weight gain than MSs in youth (ES = 0.53, CI: 0.41-0.66 versus 0.10, CI: -0.12-0.33), but not in adults (ES = 0.13, CI: 0.05-0.22 versus 0.00, CI: -0.08-0.08). However, results were heterogeneous and not significant in either age group after excluding topiramate. Nevertheless, SGA-related weight gain was significantly greater in youth than adults. In youth, SGA-related somnolence was greater than with MSs (NNH = 4.7, CI: 3.9-6.0 versus 9.5, CI: 6.3-23.5), and more likely than in adults (NNH = 7.1, CI: 6.1-8.8). Conversely, youth experienced less akathisia with SGAs than adults (NNH = 20.4, CI: 14.1-36.5 versus 10.2, CI: 8.1-13.7), likely due to lower doses/slower titration.. In treating mania, potentially greater short-term efficacy compared to placebo with SGAs versus MS needs to be balanced against increased adverse events, especially in youth.

Topics: Adolescent; Adult; Age Factors; Akathisia, Drug-Induced; Anti-Obesity Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Child; Confidence Intervals; Double-Blind Method; Female; Fructose; Haloperidol; Humans; Male; Randomized Controlled Trials as Topic; Time Factors; Topiramate; Treatment Outcome; Weight Gain; Weight Loss

Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to pathogenic adipocyte and adipose tissue responses and metabolic disease. Fat weight loss may improve adiposopathy, and thus improve metabolic disease in overweight patients. Unfortunately, the efficacy of non-surgical weight loss therapies is often limited due to redundant physiological systems that help 'protect' against starvation and/or negative caloric balance. One strategy to overcome these limitations is to combine weight loss drug therapies having complementary mechanisms of action, thereby affecting more than one physiologic process influencing body fat accumulation. Phentermine is a noradrenergic sympathomimetic amine approved for short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide derivative of the naturally occurring sugar monosaccharide D-fructose approved as a treatment for migraine headaches and seizure disorders. Although known to facilitate weight loss since its approval, topiramate monotherapy does not have a regulatory indication as an anti-obesity agent. Phentermine HCl/topiramate controlled-release (PHEN/TPM CR) is a combination agent containing immediate-release phentermine and controlled-release topiramate. Clinical trials involving thousands of patients demonstrate PHEN/TPM CR to be effective in improving the weight of patients, and also effective in improving adiposopathy-associated metabolic diseases. This review examines the pathophysiology of adiposopathy as a contributor to metabolic disease, the data supporting phentermine monotherapy, topiramate monotherapy and their combination as anti-obesity and anti-adiposopathy agents, and the preliminary evidence supporting PHEN/TPM CR as a generally well-tolerated and effective agent to improve metabolic disease.

Topics: Adipose Tissue; Adiposity; Animals; Anti-Obesity Agents; Appetite Depressants; Appetite Regulation; Delayed-Action Preparations; Drug Approval; Drug Combinations; Drugs, Investigational; Fructose; Humans; Metabolic Diseases; Obesity; Phentermine; Practice Guidelines as Topic; Sympathomimetics; Topiramate; United States; United States Food and Drug Administration; Weight Loss

Topics: Adolescent; Adult; Aged; Anticonvulsants; Anxiety Disorders; Female; Fructose; Glaucoma, Angle-Closure; Humans; Male; Middle Aged; Migraine Disorders; Myopia; Pain; Personality Disorders; Topiramate; Weight Loss

To review the evidence of weight loss with use of topiramate in patients with mood disorders.. Literature search included MEDLINE (1966-December 2003), International Pharmaceutical Abstracts (1970-December 2003), and EMBASE (1980-December 2003). Search terms included topiramate, weight loss, adverse effect, mood disorders, bipolar disorder.. Weight gain is a common adverse effect of many agents used to treat mood disorders. Topiramate has been evaluated in the management of some mood disorders, and weight loss may be a beneficial side effect in these patients. Case reports, letters to the editor, prospective investigations, and retrospective observational studies were reviewed to identify evidence of weight loss with topiramate use in patients with mood disorders.. Current evidence suggests an association between topiramate and weight loss. Based on the limited data, controlled studies need to be conducted to define the role of topiramate in patients with mood disorders who would also benefit from weight reduction.

Topics: Anticonvulsants; Clinical Trials as Topic; Fructose; Humans; Mood Disorders; Topiramate; Weight Loss

Obesity is a growing worldwide epidemic that is associated with serious medical complications. Although diet and exercise are often effective treatment in the short run, the weight lost is usually regained unless intensive intervention is maintained. Pharmacological adjunctive measures are clearly needed, and topiramate is currently being investigated as a possible new therapy for obesity. This paper reviews three clinical trials of topiramate for weight reduction in obese subjects: a 6-month dose-ranging study, a 2-year study of weight loss, and a 44-week study in subjects who had previously lost weight on a low-calorie diet. All three studies found topiramate to be significantly more efficacious than placebo. Notably, weight loss continued for 1 year and, perhaps, could have continued for a longer period. Topiramate was generally well tolerated, with adverse events being mild to moderate and mostly related to the central nervous system. Paresthesia was a frequent occurrence, but it did not lead to withdrawal of >5% of the subjects in any study.

Topics: Animals; Anti-Obesity Agents; Dose-Response Relationship, Drug; Fructose; Humans; Obesity; Randomized Controlled Trials as Topic; Time Factors; Topiramate; Weight Loss

Pharmacotherapeutic management of bipolar disorder has advanced considerably since the introduction of lithium therapy nearly 50 years ago. The sizable percentage of patients who do not respond adequately to lithium and/or are intolerant to its side effects has served as an impetus for identifying alternative pharmacotherapeutic agents. Recent advances in the understanding of the neurotransmitter systems and their receptors as it applies to treatment of bipolar disorder has, in part, led to progress in delineating applications of anticonvulsant/antiepileptic drugs (AEDs) in this area. Although the efficacy of many drugs has been evaluated in patients with this disorder, medication tolerability and adherence issues related to unfavorable side effect profiles are substantial impediments to the development of novel pharmacotherapies. The potential for excessive weight gain as a side effect of certain psychopharmacologic agents remains a concern to both clinicians and patients.. English-language literature from 1985-2001 in MEDLINE was searched for the terms bipolar disorder, anticonvulsant, antiepileptic, lithium, antipsychotic, weight, and compliance. This article reviewed current therapeutic options for bipolar disorder, including newer AEDs and atypical antipsychotic drugs, with emphasis on the issue of weight gain and possible approaches to minimizing this risk.. Certain newer AEDs are characterized by more favorable safety and tolerability profiles that include weight loss as a desirable side effect. Because bipolar disorder is associated with unacceptably high rates of relapse, recurrence, and morbidity, the concept of pharmacotherapeutic efficacy logically not only includes symptom relief but also necessarily encompasses issues related to regimen tolerability and adherence.. There is a need for guidelines to help physicians carefully formulate and individualize management plans to reach safe, effective, and cost-efficient patient outcomes. Monitoring the weight of patients with bipolar disorder and educating them regarding this issue should be standard components of any treatment plan.

Topics: Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Clinical Protocols; Female; Fructose; Humans; Lithium; Obesity; Patient Compliance; Patient Education as Topic; Topiramate; Treatment Outcome; Weight Gain; Weight Loss

To date, 1,809 individuals have been exposed to topiramate (TPM), primarily adults with partial-onset seizures. Of this total, 665 patients have been treated for more than 1 year, 177 for more than 3 years, and 67 for more than 5 years. The profile of treatment-emergent adverse reactions (TEAEs) observed with TPM at various dosages is based primarily on data from five double-blind, placebo-controlled trials in which 360 patients received TPM at target doses of 200-1,000 mg/day. Long-term safety is assessed on the basis of 1,001 patients treated with TPM in controlled and open trials for up to 5.3 years. Most of the commonly reported TEAEs were related to the central nervous system and were observed with greater frequency at dosages above the 200-600-mg/day range found to be optimal in dose ranging trials. Nephrolithiasis not requiring surgery was seen in 1.5% of patients, and mild, dose-related weight loss was associated with TPM therapy. No clinically significant treatment-related abnormalities were observed in clinical laboratory parameters or in neurologic, electrocardiographic, ophthalmologic, or audiologic tests.

Topics: Adult; Anticonvulsants; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Fructose; Humans; Incidence; Kidney Calculi; Male; Middle Aged; Multicenter Studies as Topic; Topiramate; Treatment Outcome; Weight Loss

Higher cardiovascular mortality is seen with schizophrenia due to the disorder itself and antipsychotic use. South Asians are more vulnerable to developing metabolic disorders than others. Resource-limited settings in South Asia have only a few mental health professionals, and individualised case management is mostly unavailable. Therefore, there is less monitoring and personalised support for diet and physical exercise programmes. Topiramate is useful for weight reduction and improvement of psychopathology in schizophrenia. However, there has been only one previous randomised controlled trial (RCT) done in South Asia, which possesses a quarter of the world's population.. We conducted a double-blind RCT in an outpatient setting in Sri Lanka. We compared topiramate 100 mg/day with a placebo in overweight/obese adults with schizophrenia who have been on antipsychotics for at least a year. We obtained monthly anthropometric measurements and assessed the symptomatology using the brief psychiatric rating scale (BPRS).. Fifty patients each in the topiramate and placebo arms completed the study. Topiramate add-on therapy led to significant weight/Body Mass Index reduction and improved symptomatology as measured by the BPRS compared to the placebo. The topiramate group had significantly more reporting of loss of appetite.. According to available data, this is the RCT with most participants assessing the use of topiramate in schizophrenia and only the second in South Asia. Topiramate was shown to be useful for weight reduction and symptomatic improvement in persons with schizophrenia in a resource-limited setting in South Asia.

Topics: Adult; Antipsychotic Agents; Double-Blind Method; Humans; Obesity; Overweight; Schizophrenia; Topiramate; Weight Loss

Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms.. The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and coadministered (EQW/DAPA), DAPA/extended-release (ER) metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS.. Nondiabetic women (n = 119; aged 18-45 years) with a body mass index (BMI) greater than 30 and less than 45 and polycystic ovary syndrome (National Institutes of Health criteria) were randomly assigned in a single-blinded fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000 mg XR daily), or PHEN (7.5 mg)/TPM (46 mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures, and body composition evaluated by dual-energy x-ray absorptiometry (DXA). Oral glucose tolerance tests were conducted to assess glycemia and mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), and lipid profiles were measured in the fasting sample.. EQW/DAPA and PHEN/TPM resulted in the most loss of weight and total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI, and IS. Reductions in fasting glucose, testosterone, FAI, and BP were seen with all drugs.. Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.

Topics: Adolescent; Adult; Benzhydryl Compounds; Blood Glucose; Drug Therapy, Combination; Exenatide; Female; Glucose Tolerance Test; Glucosides; Humans; Hypoglycemic Agents; Metformin; Middle Aged; Obesity; Phentermine; Polycystic Ovary Syndrome; Prospective Studies; Single-Blind Method; Topiramate; Treatment Outcome; Weight Loss; Young Adult

Schizophrenia is a psychiatric disorder with a higher mortality than that of the general population. Most of the deaths are due to cardiovascular causes and are related to metabolic risks. This risk is due not only to antipsychotics but also to inherent factors of the disorder. Studies in the West have shown topiramate to be effective in schizophrenia to reduce weight gain and for symptomatic control. Whether this is effective for South Asians is not known. It is important because South Asians have a higher risk of metabolic syndrome. We aim to conduct a double-blind, randomized controlled trial comparing topiramate add-on therapy with treatment as usual with antipsychotics in patients with schizophrenia in an outpatient setting in Sri Lanka.. Ninety patients with schizophrenia presenting to the Colombo North Teaching Hospital will be randomized to intervention and control groups equally using permuted block randomization. Patients with comorbid metabolic disorders and taking prescribed weight-controlling medications will be excluded. The intervention group will be prescribed topiramate in addition to their antipsychotics in a predefined dosing regimen targeting a dose of 100 mg per day. The control subjects are to receive a placebo. As the primary outcome, anthropometric measurements including weight, waist circumference, skinfold thickness, and body mass index will be recorded at baseline and monthly during the study period of 3 months. The secondary outcome is the change in symptoms according to the clinician-administered Brief Psychiatric Rating Scale. Assessment of capacity will be performed and informed consent obtained from all subjects. Ethics approval has been obtained from the ethical review committee of the Faculty of Medicine, University of Kelaniya, and the trial has been registered in the Sri Lanka Clinical Trials Registry.. In this double-blind, randomized controlled trial, we will attempt to assess the effectiveness of topiramate as an add-on therapy compared with treatment as usual for weight control in patients with schizophrenia. To our knowledge, this is the first such study in South Asia, where metabolic risks are found to be higher than in the West and could have unique ethnic factors related to weight gain in schizophrenia.. Sri Lanka Clinical Trials Registry, SLCTR/2017/003 . Registered on 20 February 2017. Universal trial number, U1111-1192-9439.

Topics: Anti-Obesity Agents; Antipsychotic Agents; Clinical Protocols; Double-Blind Method; Fructose; Hospitals, Teaching; Humans; Obesity; Research Design; Schizophrenia; Schizophrenic Psychology; Sri Lanka; Time Factors; Topiramate; Treatment Outcome; Weight Gain; Weight Loss

Few studies have investigated the likelihood of weight maintenance in obese persons with schizophrenia after their initial successful weight loss. This pilot open-label study examined the efficacy of topiramate in weight loss and the trajectory of weight changes after topiramate discontinuation.. This study enrolled 10 obese persons with schizophrenia. A 4-month treatment phase was started, followed by a 12-month discontinuation phase. Body weight was measured as the primary outcome every month. Secondary outcomes included leptin levels, fasting glucose, lipid profiles, and insulin resistance index.. After the 4-month addition of topiramate, participants lost 1.79 kg of their body weight (95% CI=-3.03 to -0.56, p=0.005). The maximum weight reduction was 4.32 kg, occurring when topiramate had been discontinued for 12 months (95% CI=-6.41 to -2.24, p<0.001).. The continuing weight-loss effect after topiramate discontinuation might have resulted from topiramate's potential to improve leptin functioning. These findings demonstrate that topiramate's weight-loss effect could not only persist during its administration, but also continue to improve after its discontinuation.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Female; Follow-Up Studies; Fructose; Humans; Leptin; Male; Middle Aged; Obesity; Schizophrenia; Time Factors; Topiramate; Weight Loss

Treatment algorithms for type 2 diabetes recommend weight loss for disease management. The safety and efficacy of treatment with phentermine (PHEN)/topiramate (TPM) extended release (ER) plus lifestyle modification for weight loss and glycemic benefits were assessed in two randomized, double-blind, placebo-controlled 56-week studies of obese/overweight adults with type 2 diabetes.. The OB-202/DM-230 Study was a 56-week phase 2 trial that randomized subjects to receive once-daily placebo or PHEN/TPM ER 15 mg/92 mg (15/92). The primary end point was change in HbA₁c level. A post hoc analysis of a subpopulation with type 2 diabetes from a second study, CONQUER, is also presented. All subjects made lifestyle modifications, and comorbidities were managed to the standard of care.. The study groups comprised 130 subjects with type 2 diabetes enrolled in the OB-202/DM-230 Study (mean baseline HbA₁c 8.7% [72 mmol/mol]) and 388 subjects with type 2 diabetes in the CONQUER Study (mean baseline HbA1c 6.8% [51 mmol/mol]). At week 56 in the OB-202/DM-230, change in weight (from intent-to-treat sample with last observation carried forward [ITT-LOCF]) was -2.7% for placebo and -9.4% for PHEN/TPM ER 15/92 (P < 0.0001 vs. placebo). Change in HbA1c level (from ITT-LOCF) was -1.2% (-13.1 mmol/mol) for placebo and -1.6% (-17.5 mmol/mol) for PHEN/TPM ER 15/92 (P = 0.0381). In both the OB-202/DM-230 and CONQUER, greater numbers of patients randomized to receive PHEN/TPM ER treatment achieved HbA₁c targets with reduced need for diabetic medications when compared with the placebo group. Common adverse events included paraesthesia, constipation, and insomnia.. PHEN/TPM ER plus lifestyle modification can effectively promote weight loss and improve glycemic control as a treatment approach in obese/overweight patients with type 2 diabetes.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Fructose; Humans; Life Style; Male; Middle Aged; Obesity; Phentermine; Topiramate; Treatment Outcome; Weight Loss

A 28-week, randomized, controlled trial compared the combination of phentermine and topiramate extended-release (PHEN/TPM ER) with its components as monotherapies and with placebo in obese adults.. Subjects were randomized to placebo, phentermine 7.5 mg, phentermine 15 mg, topiramate ER 46 mg, topiramate ER 92 mg, PHEN/TPM ER 7.5/46 mg, or PHEN/TPM ER 15/92 mg. All subjects received lifestyle intervention counseling. Primary endpoints were percent weight loss (WL) and achievement of ≥5% WL.. At week 28, PHEN/TPM ER 7.5/46 (-8.5%) and 15/92 (-9.2%) achieved greater percentage WL versus placebo (-1.7%; P < 0.0001) and their respective monotherapies (P < 0.05). The percentage of subjects achieving ≥5% WL was 15.5% for placebo, 43.3% for phentermine 7.5, 46.2% for phentermine 15, 39.2% for topiramate ER 46, 48.6% for topiramate ER 92, 62.1% for PHEN/TPM ER 7.5/46, and 66.0% for PHEN/TPM ER 15/92. PHEN/TPM ER was generally well tolerated; comprehensive assessment of cognitive functions with the Repeatable Battery for Assessment of Neuropsychological Status revealed impairment only in the attention domain.. PHEN/TPM ER demonstrated greater WL when used in combination than when used as monotherapies, suggesting enhanced ability of the combination formulation to induce WL at doses lower than with available monotherapies.

Topics: Adult; Anti-Obesity Agents; Delayed-Action Preparations; Drug Combinations; Female; Fructose; Humans; Male; Middle Aged; Obesity; Phentermine; Placebos; Topiramate; Treatment Outcome; Weight Loss

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

Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant weight loss compared with placebo in a 56-wk study in overweight and obese subjects with ≥2 weight-related comorbidities.. This study evaluated the long-term efficacy and safety of PHEN/TPM CR in overweight and obese subjects with cardiometabolic disease.. This was a placebo-controlled, double-blind, 52-wk extension study; volunteers at selected sites continued with original randomly assigned treatment [placebo, 7.5 mg phentermine/46 mg controlled-release topiramate (7.5/46), or 15 mg phentermine/92 mg controlled-release topiramate (15/92)] to complete a total of 108 wk. All subjects participated in a lifestyle-modification program.. Of 866 eligible subjects, 676 (78%) elected to continue in the extension. Overall, 84.0% of subjects completed the study, with similar completion rates between treatment groups. At week 108, PHEN/TPM CR was associated with significant, sustained weight loss (intent-to-treat with last observation carried forward; P < 0.0001 compared with placebo); least-squares mean percentage changes from baseline in body weight were -1.8%, -9.3%, and -10.5% for placebo, 7.5/46, and 15/92, respectively. Significantly more PHEN/TPM CR-treated subjects at each dose achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss compared with placebo (P < 0.001). PHEN/TPM CR improved cardiovascular and metabolic variables and decreased rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well tolerated over 108 wk, with reduced rates of adverse events occurring between weeks 56 and 108 compared with rates between weeks 0 and 56.. PHEN/TPM CR in conjunction with lifestyle modification may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease. This trial was registered at clinicaltrials.gov as NCT00796367.

Topics: Adult; Anti-Obesity Agents; Cardiovascular Diseases; Delayed-Action Preparations; Diabetes Mellitus; Double-Blind Method; Drug Combinations; Female; Fructose; Humans; Incidence; Intention to Treat Analysis; Least-Squares Analysis; Male; Metabolic Diseases; Middle Aged; Obesity; Overweight; Patient Dropouts; Phentermine; Time; Topiramate; Weight Loss

Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors.. In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787.. Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events.. The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors.. Vivus.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Comorbidity; Double-Blind Method; Drug Combinations; Female; Fructose; Humans; Male; Middle Aged; Obesity; Overweight; Phentermine; Topiramate; Weight Loss; Young Adult

Clozapine represents the treatment of choice for refractory psychosis, although a significant number of individuals demonstrate suboptimal response to it as well, leading to clozapine augmentation strategies. A variety of agents have been investigated in this regard, including mood stabilizers, such as anticonvulsants. Within this group of medications, topiramate is unique in that it is associated with weight loss, making it an attractive option because of clozapine's notable risk for associated metabolic disturbance. A 12-week naturalistic, open study was carried out to examine the potential benefits of topiramate in clozapine-treated individuals with schizophrenia demonstrating a suboptimal clinical response. We were specifically interested in clinical symptoms, changes in metabolic parameters, and tolerability. A total of 20 subjects were enrolled, and 16 completed the study, including 5 individuals with type 2 diabetes. Topiramate augmentation led to a 14% improvement in total Brief Psychiatric Rating Scale scores (P = 0.0003), a 2.5% decrease in body weight (P = 0.015), and was generally well tolerated, paraesthesia being the most common side effect. These findings support topiramate as a viable augmentation strategy in clozapine partial responders, with evidence of both clinical and metabolic benefits.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Schizophrenia; Topiramate; Treatment Outcome; Weight Loss

Migraine, particularly migraine with aura, and increased body weight are independent risk factors for cardiovascular disease (CVD). The association of weight change and clinical markers of CVD risk was evaluated in subjects participating in a randomized double-blind, parallel-group study of migraine-preventive treatment comparing 100 mg/day of topiramate and amitriptyline. Individuals from both treatment groups were pooled and stratified into three groups. The 'major weight gain' group gained > or = 5% of their baseline body weight at the conclusion of the study; the 'major weight loss' group lost > or = 5% of their baseline body weight. The third group had < 5% of weight change. The influence of weight change in headache outcomes, as well as in markers of CVD (blood pressure, cholesterol, C-reactive protein), was assessed using analysis of covariance. Of 331 subjects, 52 (16%) experienced major weight gain and 56 (17%) experienced major weight loss. Weight change was not associated with differential efficacy for the treatment of headache. However, contrasted with those with major weight loss, those who gained weight experienced elevations in mean diastolic blood pressure (+2.5 vs. -1.2 mmHg), heart rate (+7.6 vs. -1.3 beats per minute), glycosylated haemoglobin (+0.09% vs. -0.04%), total cholesterol (+6.4 vs. -6.3 mg/dl), low-density lipoprotein cholesterol (+7.0 vs. -4.4 mg/dl) and triglycerides (+15.3 vs. -10.4 mg/dl) and an increase in high-sensitivity C-reactive protein (+1.8 vs. -1.9 mg/l). Both groups experienced decreases in systolic blood pressure (-4.0 vs. -1.3 mmHg) and high-density lipoprotein cholesterol (-3.7 vs. -0.8 mg/dl). Increased weight during migraine treatment is not associated with poor headache treatment outcomes, but is associated with deterioration of CVD risk markers.

Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cholesterol, HDL; Double-Blind Method; Female; Fructose; Humans; Male; Migraine Disorders; Risk Factors; Topiramate; Weight Gain; Weight Loss

We previously tested topiramate, an anticonvulsant, in the treatment of aggression in men with borderline personality disorder (BPD) (Nickel M, Nickel C, Kaplan P, Lahmann C, Mühlbacher M, Tritt K, et al. Treatment of aggression with topiramate in male borderline patients: a double-blind, placebo-controlled study. Biol Psychiatry 2005;57:495-9), and found significant changes on most scales of the state-trait anger expression inventory (STAXI) and significant weight loss eight weeks later. The aim of this trial was to assess topiramate's efficacy in the long-term therapy for aggression in men with BPD.. This 18-month follow-up observation, in which the previous patients (topiramate group: n=22; former placebo group: n=22) were examined bianually, was carried out.. According to the intent-to-treat principle, significant changes on all scales of the STAXI were observed in the subjects treated with topiramate. Additional significant weight loss was observed. All subjects tolerated topiramate relatively well.. Topiramate appears to be an effective, relatively safe agent in the long-term treatment of patients with BPD. Mild, non-transient weight loss can be expected.

Topics: Adult; Aggression; Anger; Anticonvulsants; Borderline Personality Disorder; Double-Blind Method; Follow-Up Studies; Fructose; Humans; Male; Personality Inventory; Topiramate; Weight Loss

To investigate the efficacy and safety of topiramate in obese subjects with type 2 diabetes treated with metformin.. This was a multicenter, double-blind, placebo-controlled trial. All subjects received a non-pharmacological program of diet, exercise and behavioral modification throughout the study; the assigned diet was 600 kcal/day less than the subject's individually calculated energy expenditure. After a 6-week single-blind placebo run-in, subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Following an 8-week titration period, subjects remained on their assigned dose for 52 weeks. However, the sponsor ended the study early in order to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. A total of 646 obese men and women (age: 18-75 years, body mass index: 27-50 kg/m(2)) with an established history of type 2 diabetes mellitus controlled by metformin monotherapy were randomized. Efficacy was assessed in a pre-determined modified intent-to-treat (MITT) population of 307 subjects whose randomization date would have allowed them to complete 24 weeks on study medication before the announcement of study termination.. Joint primary efficacy parameters were mean percent change in weight and change in glycosylated hemoglobin (HbA(1c)) from baseline to week 24.. Subjects in the placebo, topiramate 96 mg/day and topiramate 192 mg/day groups lost 1.7%, 4.5% (P<0.001) and 6.5% (P<0.001), respectively, of their baseline body weight and had absolute decreases in HbA(1c) of 0.1%, 0.4% (P<0.001) and 0.6% (P<0.001) (MITT, last observation carried forward). Topiramate-treated subjects also experienced statistically significant decreases in systolic blood pressure. Most common adverse events were paresthesia and events related to the central nervous system.. Topiramate was effective for weight reduction and improvement in glycemic control in obese subjects with type 2 diabetes treated with metformin monotherapy. Further study in obese diabetics is warranted.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Obesity; Topiramate; Treatment Outcome; Weight Loss

Topiramate (TPM) has been reported to reduce body weight beyond a placebo in the treatment of obese participants, but the effect of this agent on components of energy balance has not yet been established in humans. Thus, the aim of this study was to study the impact of TPM on food preferences, measures of satiety, food intake, resting metabolic rate (RMR), and 24-h energy expenditure.. The study design consisted of a 6-month, single-center, randomized, double-blind, parallel group, placebo-controlled trial with a 6-month open-label extension. The study included 68 sedentary men with abdominal obesity (waist circumference > or = 100 cm), of between 25 and 55 years of age, with a dyslipidemic profile and a body mass index (BMI) > or = 27 and < or = 40 kg/m(2).. Treatment with TPM produced significant changes in anthropometric variables and body composition compared with placebo. However, at the end of the 1-year study, the placebo/TPM group showed similar weight loss and reduction in body fatness compared with the TPM/TPM group. For instance, at the end of the 12-month intervention, mean percentage of body weight loss from baseline was about -5% in both groups (-4 kg fat loss). Topiramate treatment reduced energy intake, be it in the context of an ad libitum buffet-type meal or under free living conditions. The 24-h daily energy expenditure (DEE) assessed by whole-body indirect calorimetry adjusted for body weight and age was not altered by TPM treatment.. Topiramate treatment produced significantly greater weight loss than placebo and the majority of this loss was explained by a decrease in body fat stores. Most of the weight loss effect produced by TPM therapy was observed within a period of 6 months. Finally, TPM treatment had an impact on energy balance through a reduction in food intake that appears to have created an energy deficit of about 30,000-40,000 kcal compared with treatment with the placebo over 6 months.

Topics: Adipose Tissue; Adult; Anti-Obesity Agents; Calorimetry, Indirect; Double-Blind Method; Energy Intake; Energy Metabolism; Food Preferences; Fructose; Humans; Male; Middle Aged; Obesity; Satiety Response; Topiramate; Weight Loss

To examine the metabolic effects and body composition changes after topiramate treatment of obese type 2 diabetic patients (DM2) for 11 months.. Thirty-eight DM2 on diet or sulfonylurea treatment participated in this randomized double-blind placebo-controlled trial. Thirteen placebo-treated and nine topiramate-treated patients completed the trial. Patients were randomized to treatment with topiramate 96 mg b.i.d. or placebo (6-week run-in phase, 2-months titration phase, 9-months maintenance phase).. Insulin sensitivity was measured with euglycaemic hyperinsulinemic clamps. Weight, HbA1c, fasting glucose, blood lipids and safety variables were measured at regular intervals. Body composition was determined with computerized tomography. Meal tests were performed to evaluate postprandial glucose and insulin levels. Three-day diet recalls were carried out to evaluate energy ingestion.. The mean age was 58.6+/-7.1 years, body weight 98.1+/-16.1 kg, BMI 33.0+/-4.5 kg/m(2), and glycosylated hemoglobin (HbA1c) 7.3+/-0.9%. In topiramate-treated patients, there were significant reductions in HbA1c (1.1+/-0.9%), fasting plasma glucose, body weight (-6.6+/-3.3%), as well as body fat, lean body mass, postprandial glucose and free fatty acid levels but there were no significant changes in insulin sensitivity. The daily average energy intake decreased more in the topiramate group than in the placebo group. Paresthesia and central nervous system-related side effects were the main causes for the dropout rate.. Topiramate treatment of overweight DM2 reduced body weight and body fat, and was associated with a marked improvement in glycaemic control whereas no significant improvement in insulin-stimulated glucose uptake was demonstrated. Further studies are required to clarify whether this effect might occur through changes in insulin sensitivity in the liver and/or pancreatic insulin secretion.

Topics: Adipocytes; Adult; Aged; Anti-Obesity Agents; Body Composition; Cells, Cultured; Cytokines; Diabetes Mellitus, Type 2; Dietary Fats; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Middle Aged; Obesity; Overweight; Placebos; Sulfonylurea Compounds; Topiramate; Weight Loss

To examine efficacy and tolerability of topiramate as an adjunctive treatment for overweight refractory bipolar patients.. Patients (n=30) with Bipolar I or II, were provided with an open label treatment with topiramate as an add-on therapy. All patients deemed refractory to at least one mood stabilizer, were overweight, and were treated with topiramate as an adjuvant to existing medication for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression Scale (CGI). Other scales included the Young's Mania Rating Scale (YMRS), and the Hamilton Depression scale (HAMD21). Measures prior to adding topiramate were compared to those repeated at 4, 8 and 12 weeks. Tolerance, and weight changes were monitored.. There was significant reduction in both depressive and manic symptoms with adjunctive treatment. The mean BMI at 12 weeks of topiramate treatment dropped by 2 points (p<0.0001).. Topiramate is an effective adjunctive treatment in bipolar refractory patients and the significant weight reduction effects may result in important medical risk reductions, and make topiramate attractive for some obese bipolar patients.

Topics: Adult; Anti-Obesity Agents; Bipolar Disorder; Drug Resistance; Female; Fructose; Humans; Male; Obesity; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome; Weight Loss

The aim of this study was to examine the efficacy and safety of topiramate as an adjunct to diet and exercise in drug-naive, obese subjects with type 2 diabetes.. Drug-naive individuals with type 2 diabetes, body mass index (BMI) of > or =27 and <50 kg/m(2) and haemoglobin A(1c) (HbA(1c)) of <10.5% were enrolled into the study. All the individuals participated in a non-pharmacologic weight loss program (Pathways to Change((R)); Johnson & Johnson Healthcare Systems, Piscataway, NJ, USA) throughout the trial. After a 6-week placebo run-in, the subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Subjects were scheduled for 8-week titration and 52-week maintenance phases. The study was ended early; efficacy data were reported for a predefined modified intent-to-treat (MITT) population (n = 229), with 40 weeks of treatment. All the subjects who provided any safety data were included in the safety population (n = 535).. Baseline mean weight was 103.7 kg, BMI 36 kg/m(2) and HbA(1c) 6.7% across all treatment groups. By the end of week 40, the placebo, the topiramate 96 mg/day and topiramate 192 mg/day groups lost 2.5, 6.6 and 9.1% of their baseline body weight respectively (p < 0.001 vs. placebo, MITT population using last observation carried forward). The decrease in HbA(1c) was 0.2, 0.6 and 0.7% respectively (p < 0.001 vs. placebo, MITT). Topiramate significantly reduced blood pressure and urinary albumin excretion; a weight-loss-independent HbA(1c) improving effect of topiramate was demonstrated. Adverse events were predominantly related to central nervous system (CNS).. Topiramate as an add-on treatment to lifestyle improvements produced significant weight loss and improved glucose homeostasis in obese, drug-naive subjects with type 2 diabetes. These treatment advantages should be balanced against the occurrence of adverse events in the CNS.

Topics: Albuminuria; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Fructose; Glycated Hemoglobin; Humans; Lipid Metabolism; Male; Middle Aged; Nervous System Diseases; Obesity; Topiramate; Treatment Outcome; Weight Loss

This study focused on (i) evaluating the long-term tolerability and safety of topiramate in Chinese patients with epilepsy, and (ii) comparing the tolerability and safety of topiramate monotherapy versus polytherapy in the same population.. This was a prospective, open-label, long-term (36 months) clinical trial. 320 patients (275 adults and 45 children) with epilepsy were recruited into the study; of these, 156 patients had generalised seizures, 151 patients had partial seizures and 13 patients had unclassifiable seizures. All patients received topiramate approximately 200 mg/day either as monotherapy or as adjunctive therapy. At each visit, a physical examination and routine laboratory analysis were performed, and the adverse event (AE) profile was obtained by face-to-face interview.. 268 patients received topiramate

Topics: Adolescent; Adult; Anticonvulsants; Child; China; Dizziness; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Longitudinal Studies; Male; Memory Disorders; Paresthesia; Prospective Studies; Topiramate; Weight Loss

In a randomized controlled trial, we compared the efficacy of topiramate versus placebo in women undergoing olanzapine therapy and found that topiramate effectively contributed to weight loss in short-term treatment and had a positive effect on health-related quality of life, the patients' actual state of health, and psychological impairments. The aim of this observational study was to assess whether topiramate has a sustained benefit in long-term treatment of olanzapine-associated weight gain in subjects who had participated in the previous randomized controlled trial comparing topiramate with placebo. The subjects (topiramate group, n = 25; former placebo group, n = 18) were observed in an 18-month open-label study. After unblinding, subjects from the former topiramate group continued treatment with topiramate, whereas subjects from the former placebo group received neither placebo nor topiramate. The subjects were seen every 6 months, weighed, and tested with the SF-36 Health Survey, Scale of Well-Being, and the Adjective Checklist. According to the intent-to-treat principle, the repeated-measures analysis showed a significant interaction for the group-by-time effect for change of weight (P < 0.01) on the Scale of Well-Being (P < 0.01), all scales of the Adjective Checkist (all P < 0.01), and 5 scales (physical functioning, role limitations due to physical health, social functioning, mental health, and vitality) of the SF-36 Health Survey (all P < 0.01). Topiramate was well tolerated and seems to be effective and safe in the long-term treatment of olanzapine-related adiposity in women. Furthermore, positive changes in the patients' state of health, psychological impairments, and health-related quality of life could be also observed.

Topics: Adiposity; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Female; Follow-Up Studies; Fructose; Humans; Olanzapine; Quality of Life; Topiramate; Weight Gain; Weight Loss

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 is a common and severe psychiatric illness. The goal of this study was to determine whether topiramate can influence patients' borderline psychopathology, health-related quality of life, and interpersonal problems. Women meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Structured Clinical Interview II criteria for borderline personality disorder were randomly assigned in a 1:1 ratio to topiramate titrated from 25 to 200 mg/d (n = 28) or placebo (n = 28) for 10 weeks. Primary outcome measures were changes on the Symptom-Checklist, on the SF-36 Health Survey, and on the Inventory of Interpersonal Problems. Body weight and additional side effects were assessed weekly. According to the intent-to-treat principle, significant changes (all P < 0.001) on the somatization, interpersonal sensitivity, anxiety, hostility, phobic anxiety, and Global Severity Index scales of the Symptom Checklist were observed in the topiramate-treated subjects after 10 weeks (no significant changes on the obsessive-compulsive, depression, paranoid ideation, and psychoticism scales). In the SF-36 Health Survey, significant differences were observed on all 8 scales (all P < 0.01 or P < 0.001). In the Inventory of Interpersonal Problems, significant differences (all P < 0.001) were found in the scales for overly autocratic, overly competitive, overly introverted, and overly expressive (no significant differences in the scales for overly cold, overly subassertive/subservient, overly exploitable/compliant, and overly nurturant/friendly). Weight loss was additionally observed (p < 0.001). Topiramate appears to be a safe and effective agent in the treatment in women with borderline personality disorder. Additional weight loss can be expected.

Topics: Adolescent; Adult; Anger; Anticonvulsants; Anxiety; Borderline Personality Disorder; Double-Blind Method; Female; Fructose; Humans; Interpersonal Relations; Personality Inventory; Placebos; Psychiatric Status Rating Scales; Quality of Life; Topiramate; Weight Loss

The weight-gain caused by many psychotropic drugs is a major cause for poor compliance with such medications and could also increase cardio-vascular morbidity among psychiatric patients. Recent reports have shown that the anticonvulsant topiramate causes weight loss in various patient groups. The drug has also shown effectiveness in open trials as a mood stabilizer in patients with affective disorders, but not in controlled trials in the acute treatment of mania. We used topiramate to treat 12 patients with affective disorders who had a body-mass index > 30 kg/m2.. Topiramate was prescribed as part of our routine clinical practice, as an add-on medication, or as a replacement of a mood stabilizer. Patients' weight was recorded in 1 to 2 monthly intervals. Patients were followed up for between 6 and 12 months. The final dose of topiramate varied from 200 to 600 mg/day.. Topiramate was effective in reducing the weight in 10 out of the 12 patients. At six months the 12 patients had lost a mean of 7.75 kg (SD = 6.9 kg, p < 0.001) and at 12 months 9 patients had lost a mean of 9.61 kg (SD = 6.7 kg, p = 0.003). Three patients stopped the treatment: one due to side effects, one due to possible side effects, and one suffered a manic relapse and showed no sustained weight loss. There were no other clear changes in the course of illness of the patients.. The evidence of a strong weight-reducing potential of topiramate is indisputable and clinically significant. Topiramate could be considered in the treatment of bipolar patients who are overweight, or whose concerns about weight gain compromise their compliance with long-term prophylactic medication. So far there is no evidence that topiramate has anti-manic effect and it should not be used as monotherapy.

Topics: Adult; Aged; Anti-Obesity Agents; Anticonvulsants; Bipolar Disorder; Body Mass Index; Case-Control Studies; Comorbidity; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Mood Disorders; Obesity; Psychotropic Drugs; Topiramate; Weight Loss

The aim of this study was to compare the efficacy of topiramate versus a placebo in the treatment of adiposity in women undergoing olanzapine therapy. We also assessed changes health-related quality of life, the patient's actual state of health, and psychologic impairments. The 10-week, random, double-blind, placebo-controlled study included 43 women who had been treated with olanzapine (mean dose 7.8 +/- 3.6 in the topiramate group and 7.2 +/- 3.1 in the placebo group) and had gained weight as a side effect. The subjects were randomly assigned to topiramate (n = 25) or a placebo (n = 18). Primary outcome measures were weight checks and self-reported changes on the scales of the SF-36 Health Survey, Bf-S Scale of Well-Being, and the Adjective Checklist EWL-60-S. Weight loss was observed and was significantly more pronounced in the topiramate-treated group (difference in weight loss between the 2 groups: 5.6 kg, 95% CI = -8.5, -3.0, P < 0.001). In comparison with the placebo group, significant changes on 7 (7/8) scales of SF-36 Health Survey (all P < 0.001), on all 6 scales of the EWL-60-S, and on the Bf-S were observed in the topiramate-treated subjects after 10 weeks. All patients tolerated topiramate well. Topiramate appears to be a safe and effective agent in the treatment of weight gain that occurred during olanzapine treatment. Significantly positive changes in health-related quality of life, the patient's actual state of health, and psychologic impairments were observed.

Topics: Adipose Tissue; Adult; Anti-Obesity Agents; Benzodiazepines; Confidence Intervals; Double-Blind Method; Female; Fructose; Humans; Mental Disorders; Neuropsychological Tests; Olanzapine; Statistics, Nonparametric; Topiramate; Weight Gain; Weight Loss

Depression is associated with increased aggression and diminished ability and quality of life. The goal of this study was to compare the efficacy of topiramate in influencing depressive symptoms, aggression, ability, and health related quality of life in depressive women.. We conducted a randomized, double-blind, placebo-controlled 10-week study of topiramate in 64 female subjects from the general population who met criteria for recurrent major depressive disorder. Primary outcome measures were changes on the Hamilton Depression Rating Scale (HDRS), the State-Trait Anger Expression Inventory (STAXI), the Test of Attention (d2), and the SF-36 Health Survey (SF-36).. According to the intent-to-treat principle, a significant difference on the HDRS (P=0.02), all scales of STAXI (all P<0.001), Total efficiency of d2 (P<0.001), and on most scales of SF-36 (P between 0.15 and <0.001) were observed in the topiramate-treated subjects comprised the placebo group. The reduction in expression of anger correlated significantly with changes on the HDRS, and several scales of d2 and SF-36. Additional weight loss, which was significantly more pronounced in the topiramate group than in those treated with a placebo, was ascertained (difference in weight loss between the two groups: 4.2 kg, P<0.001). All the patients tolerated topiramate relatively well.. Only moderately ill women were included.. Topiramate appears to be an effective agent in the reduction of depressive symptoms and anger and in the improvement of ability and health-related quality of life in depressive women. Additional weight loss can be expected.

Topics: Adult; Anger; Anticonvulsants; Depressive Disorder, Major; Double-Blind Method; Female; Follow-Up Studies; Fructose; Humans; Surveys and Questionnaires; Topiramate; Weight Loss

The effect of topiramate on weight and blood pressure (BP) was examined in a randomized, placebo-controlled trial in obese subjects who had hypertension. After a 4-week, placebo, run-in period, 531 obese subjects (body mass index 27 to 50 kg/m(2)) who had established hypertension were randomly assigned to placebo or 96 or 192 mg/day of topiramate. All subjects received a standardized diet, exercise advice, and behavioral modification from run-in through study end. Initially scheduled for 60 weeks on medication, the sponsor ended the study early to develop a new controlled-release formulation. As a consequence, efficacy was assessed within a predefined modified intent-to-treat population (subjects who enrolled early enough to potentially complete 28 weeks on medication). The placebo and 96- and 192-mg groups had respective weight losses of 1.9%, 5.9%, and 6.5% from baseline (p <0.001 for each comparison with placebo) and decreases in diastolic BP of 2.1, 5.5, and 6.3 mm Hg (p <0.015 vs placebo). Systolic BP was decreased by 8.6 and 9.7 mm Hg in the 96- and 192-mg groups and 4.9 mm Hg in the placebo group (p = NS). Compared with placebo, the topiramate groups had larger proportions of subjects whose weight decreased by > or =5% and 10%, whose diastolic BP decreased by > or =5 and 10 mm Hg, and who achieved normalization of BP (BP <130/85 mm Hg). Adverse events included paresthesia, fatigue, taste perversion, loss of appetite, and difficulty with concentration and attention. In conclusion, topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects.

Topics: Administration, Oral; Adult; Anti-Obesity Agents; Body Mass Index; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Fructose; Humans; Hypertension; Male; Middle Aged; Obesity; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Topiramate; Treatment Outcome; Weight Loss

Small open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for migraine prevention.. To assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial.. A 26-week, randomized, double-blind, placebo-controlled study was conducted during outpatient treatment at 52 North American clinical centers. Patients were aged 12 to 65 years and had a 6-month history of migraine (International Headache Society criteria) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospective baseline phase.. After a washout period, patients meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever was less. Patients continued receiving that dose for 18 weeks.. The primary efficacy measure was change from baseline in mean monthly migraine frequency. Secondary efficacy measures included responder rate (proportion of patients with > or =50% reduction in monthly migraine frequency), reductions in mean number of monthly migraine days, severity, duration, and days a month requiring rescue medication, and adverse events. The month of onset of preventive treatment action was assessed.. Of 483 patients randomized, 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population. Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d (-2.1, P =.008) and topiramate at 200 mg/d (-2.4, P<.001) vs placebo (-1.1). Statistically significant reductions (P<.05) occurred within the first month with topiramate at 100 and 200 mg/d. The responder rate was significantly greater with topiramate at 50 mg/d (39%, P =.01), 100 mg/d (49%, P<.001), and 200 mg/d (47%, P<.001) vs placebo (23%). Reductions in migraine days were significant for the 100-mg/d (P =.003) and 200-mg/d (P<.001) topiramate groups. Rescue medication use was reduced in the 100-mg/d (P =.01) and 200-mg/d (P =.005) topiramate groups. Adverse events resulting in discontinuation in the topiramate groups included paresthesia, fatigue, and nausea.. Topiramate showed significant efficacy in migraine prevention within the first month of treatment, an effect maintained for the duration of the double-blind phase.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Double-Blind Method; Female; Fructose; Humans; Linear Models; Male; Middle Aged; Migraine Disorders; Topiramate; Weight Loss

To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low-calorie diet.. Obese subjects (30 < or = BMI < 50 kg/m(2)) 18 to 75 years old received a low-calorie diet for 8 weeks. Those who lost > or =8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination.. Of the 701 subjects enrolled, 80% lost > or =8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run-in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system.. During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low-calorie diet-and produced additional clinically significant weight loss beyond that achieved by a low-calorie diet.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Combined Modality Therapy; Diet, Reducing; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Obesity; Paresthesia; Safety; Topiramate; Treatment Outcome; Weight Loss

The goal of this study was to compare the efficacy and safety of topiramate versus placebo in the treatment of aggression in women who meet the criteria for borderline personality disorder.. We conducted a double-blind, placebo-controlled study of topiramate in 29 female subjects (response rate 93.5%) meeting SCID (Structured Clinical Interview for DSM-IV) criteria for borderline personality disorder. The subjects were randomly assigned in a 2:1 ratio to topiramate (N = 21, analysis based on N = 19) or placebo (N = 10). Treatment lasted 8 weeks (November 2003-January 2004). Primary outcome measures were self-reported changes on the anger subscales of the State-Trait Anger Expression Inventory (STAXI).. Significant improvements on 4 subscales of the STAXI (state-anger, trait-anger, anger-out, anger-control) were observed in the topiramate-treated subjects after 8 weeks, in comparison with the placebo group. The difference in improvement in score between the 2 groups for state-anger, trait-anger, and anger-out ranged from 21% to 24%, and the difference for anger-control was -13%. As an exception, a difference of only 8.5% (p < .2) was found on the anger-in subscale. Significantly greater weight loss was observed in the topiramate-treated group than in those treated with placebo (difference in weight loss between the 2 groups: 2.3 kg [5.1 lb] [3.2%]; 95% CI = 1.3% to 4.4%, p < .01). All patients tolerated topiramate well.. Topiramate appears to be a safe and effective agent in the treatment of anger in women with borderline personality disorder as defined by SCID criteria. Additionally, significant weight loss can be expected.

Topics: Adult; Aggression; Anger; Anticonvulsants; Borderline Personality Disorder; Double-Blind Method; Female; Fructose; Humans; Placebos; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome; Weight Loss

Selective serotonin reuptake inhibitors (SSRIs) are the current gold standard in the pharmacologic treatment of generalized social phobia. SSRIs are only effective in approximately 50% of individuals with generalized social phobia and can be associated with significant side effects. Based on the successful use of the anticonvulsants gabapentin and pregabalin in treating generalized social phobia, we conducted an open trial examining the efficacy of the glutamatergic and GABAergic anticonvulsant topiramate in the treatment of generalized social phobia.. Twenty-three adult outpatients with DSM-IV social phobia, generalized type, were entered into a 16-week open trial of topiramate, starting at 25 mg/day, and gradually titrated up to a maximum dose of 400 mg/day.. Twelve of 23 patients completed the trial. In the intent-to-treat (ITT) analysis, 11 (47.8%) of 23 were responders by a Clinical Global Impressions Improvement (CGI-I) scale rating of "much" or "very much" improved. The mean drop in the Liebowitz Social Anxiety Scale (LSAS) score for the ITT group was 29.4%. The change in LSAS score from baseline to endpoint was significant for the ITT group (F = 3.44, df = 4,110; p = .01). In the completers group, 9 (75.0%) of 12 were responders by CGI-I at 16 weeks, with a mean drop in LSAS score of 45.1%. The rate of remission in the ITT sample, using a definition of an LSAS score of

Topics: Adult; Age of Onset; Anticonvulsants; Comorbidity; Drug Administration Schedule; Female; Fructose; Headache; Humans; Male; Mental Disorders; Middle Aged; Paresthesia; Phobic Disorders; Psychiatric Status Rating Scales; Severity of Illness Index; Topiramate; Treatment Outcome; Weight Loss

We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults.. In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial-onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment.. In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) >/= 30 kg/m(2)], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007).. Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.

Topics: Adult; Anticonvulsants; Blood Glucose; Body Composition; Body Mass Index; Cholesterol; Energy Intake; Epilepsy; Female; Fructose; Glucose Tolerance Test; Humans; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Regression Analysis; Topiramate; Weight Loss

Prader-Willi syndrome is a neurologic disorder caused by a mutation on chromosome 15. It is characterized by short stature, obesity, mild-to-moderate mental retardation, and multiple behavior problems including mood, self-abusive behavior, and compulsive-eating disorder. These behaviors have detrimental effects on the mental and physical health of patients with Prader-Willi syndrome. This study evaluates the effectiveness of a new antiepileptic medication, topiramate, on behavior, mood, and compulsive-eating disorder associated with Prader-Willi syndrome. Recent studies have indicated that topiramate affects behavior, as well as reducing appetite and weight in some patients. We evaluated seven patients with Prader-Willi syndrome and determined that, in these patients, topiramate appeared to have a positive effect on reducing self-abusive behavior, improving mood, and stabilizing weight.

Topics: Adolescent; Affect; Anticonvulsants; Child; Compulsive Behavior; Feeding Behavior; Female; Fructose; Humans; Male; Prader-Willi Syndrome; Satiety Response; Topiramate; Treatment Outcome; Weight Loss

To evaluate the efficacy and safety of topiramate (TPM) for weight loss in healthy obese subjects.. A randomized, double-blind, placebo-controlled, dose-ranging trial was conducted. Three hundred eighty-five subjects, 18 and 75 years of age, were randomized to receive either placebo or TPM at 64, 96, 192, or 384 mg daily. Dosing began at 16 mg once daily. In week 2, the dose was increased to 16 mg twice daily. Thereafter, the dose was raised every week by 32 mg/d (16 mg twice daily) until subjects reached their target dose. Twenty-four weeks after beginning treatment, all subjects were tapered off treatment by a dose reduction of 50% per week. All participants received the same lifestyle program.. Mean percent weight loss from baseline to week 24 was -2.6% in placebo-treated patients vs. -5.0%, -4.8%, -6.3%, and -6.3% in the 64, 96, 192, and 384 mg/d TPM groups, respectively. Greater percentages of TPM-treated patients lost at least 5% or 10% of body weight compared with placebo. The most frequent adverse events were related to the central or peripheral nervous system, including paresthesia, somnolence, and difficulty with memory, concentration, and attention. Most events were dose-related, occurred early in treatment, and usually resolved spontaneously; only 21% receiving TPM withdrew due to adverse events compared with 11% on placebo.. TPM produced significantly greater weight loss than placebo at all doses.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Blood Pressure; Body Mass Index; Cardiovascular System; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Obesity; Placebos; Risk Factors; Time Factors; Topiramate; Weight Loss

Sleep-related eating disorder (SRED) and nocturnal eating syndrome (NES) combine features of sleep disorders and eating disorders. Treatment of these nocturnal eating behaviors has been directed towards underlying identifiable sleep or eating disorders using dopaminergic or opioid agonists, as well as anorectic agents, at times with the addition of sedatives.. Two patients with SRED and two with NES, who had failed multiple previous trials of pharmacotherapy and psychotherapy, were treated in a naturalistic, open-label fashion with topiramate at night. Reduction in nocturnal eating was graded based on self-report. Weight was computed at the outset of, and during, topiramate treatment.. One patient with NES had a complete elimination of nocturnal eating with topiramate, two patients (one with NES, one with SRED) had a marked response, and one patient (with SRED) had a moderate response. Mean dose was 218 mg, though three patients noted an improvement at 100 mg. Notable weight loss was observed in all patients (mean of 11.1 kg). Benefits of topiramate treatment have been maintained for a mean period of 8.5 months.. Topiramate may be of benefit for patients with NES or SRED in reducing nocturnal eating, improving nocturnal sleep, and producing weight loss.

Topics: Adult; Anti-Obesity Agents; Dyssomnias; Feeding and Eating Disorders; Female; Fructose; Humans; Male; Middle Aged; Topiramate; Treatment Outcome; Weight Loss

A 3-month open-label pilot study was carried out to assess the safety, tolerability, and effect of the antiepilectic topiramate on the cosmetic appearance of scars. Ten adult subjects with discolored or raised scars at least 2 years old were given an oral dosage of 15 mg per day of topiramate for 1 month. The dosage was then increased to 30 mg per day if there was minimal or no improvement. The safety of topiramate was assessed in this study by reviewing adverse events and vital signs. Efficacy outcomes included a Clinician Global Impression Scale (CGI) to document changes such as thickness and color. Digital photos were taken with consistent variables. In addition, two independent medical reviewers blindly reviewed the photos. The Rosenberg Self-Esteem Scale was done at each visit to measure patients' levels of self-esteem. Side effects were generally mild with the most common being language problems (n = 3) and sleep disturbances (n = 3). All subjects completed the study and experienced at least minimal thinning and decreased coloration (usually redness) of their scars. Based on CGI-assessment data at 3 months, two subjects were very much improved, four were much improved, and four had minimal improvement. One independent medical reviewer arranged before and after treatment picture sets for ten out of ten subjects. The other independent medical reviewer arranged before and after treatment pictures sets for nine out of ten subjects (both p-values less than 0.025). The data indicate that topiramate may be a safe and effective treatment for scar therapy.

Topics: Administration, Oral; Adult; Cicatrix; Female; Fructose; Humans; Male; Mental Disorders; Middle Aged; Pilot Projects; Safety; Self Concept; Single-Blind Method; Topiramate; Treatment Outcome; Weight Loss

This study was to evaluate the efficacy and safety of topiramate (TPM) in refractory partial epilepsy in children, adolescents and young adults.. We performed a prospective open label add-on study in 55 patients (age 2-30 years, mean 15 years) with refractory partial seizures. Topiramate was added to one or two other baseline drugs and the efficacy was rated according to seizure type and frequency.. TPM was initiated at a daily dose of 0.5-1 mg/kg, followed by a 2-week titration at increments of 1-3 mg/kg/24h, up to a maximum daily dose of 12 mg/kg. After 9 months of treatment, 11 patients (20%) had 100% fewer seizures and 25 patients (45%) had a more than 50% seizure reduction. TPM appeared to be effective both in cryptogenic (76.2%) and symptomatic (58.8%) partial epilepsies. Mild to moderate adverse events were present in 25 patients (45.4%), mostly represented by drowsiness, nervousness and hyporexia with or without weight loss.. TPM was an overall effective and safe add-on drug both in cryptogenic and symptomatic childhood refractory partial seizures, the adverse reactions being generally mild or moderate.

Topics: Adolescent; Adult; Child; Child, Preschool; Epilepsies, Partial; Female; Fructose; Humans; Male; Neuroprotective Agents; Prospective Studies; Psychoses, Substance-Induced; Topiramate; Weight Loss

A total of 292 adult patients (mean age, 33 years) with partial and/or generalized seizures previously resistant to antiepileptic drug (AED) therapy (median baseline seizure rate, 12 seizures/month) were treated with open-label topiramate (TPM) in dosages of 100-1,600 mg/day.. The mean duration of TPM treatment was 413 days (range, 84-804 days), and the mean TPM dosage was 503 mg/day (range, 100-1,600 mg/day; median TPM dosage, 300 mg/day). Seizure reduction was calculated from seizure counts during the last 3 months and last 6 months of TPM therapy compared with baseline.. Overall, >50% of patients achieved > or =50% seizure reduction. More important, 11% of patients were seizure-free for > or =3 months at the last visit; 10% of patients were seizure free for > or =6 months at the last visit. This robust therapeutic response was consistent for patients receiving TPM dosages >400 and <400 mg/day. The most commonly reported adverse events were related to the central nervous system. Over the 2.2-year treatment period, 19% of patients discontinued TPM therapy because of inadequate seizure control; 32% discontinued because of adverse events. Findings from this study show that TPM is a useful agent for long-term seizure control, with some patients becoming seizure free for extended periods despite failing previous AED therapy.

Topics: Adolescent; Adult; Aged; Anorexia; Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Fatigue; Female; Fructose; Headache; Humans; Incidence; Male; Middle Aged; Placebos; Sleep Wake Disorders; Topiramate; Treatment Outcome; Weight Loss

Reduced appetite and weight loss were found in clinical trials of topiramate for epilepsy. Binge-eating disorder is characterized by recurrent episodes of binge eating that are not associated with regular use of inappropriate compensatory behaviors. Overweight and obesity may be common complications. To explore the effectiveness and tolerability of topiramate in binge-eating disorder, we describe the response of 13 consecutive outpatients with binge-eating disorder to naturalistic, open-label treatment with topiramate.. The response of 13 female outpatients with binge-eating disorder by DSM-IV criteria to naturalistic, open-label treatment with topiramate (100-1400 mg/day) was reviewed. Response of binge-eating disorder symptoms was clinically assessed as none, mild, moderate, marked, or remission. Weight and side effects were also evaluated.. All 13 patients had comorbid Axis I psychiatric disorders along with binge-eating disorder and were receiving psychotropic medications at the time of topiramate administration. After beginning topiramate treatment, 9 patients displayed a moderate or better response of binge-eating disorder symptoms that was maintained for periods ranging from 3 to 30 months (mean +/- SD = 18.7+/-8.0 months). Two other patients displayed moderate or marked responses that subsequently diminished. The remaining 2 patients had a mild or no response. The mean +/- SD weight of the 13 patients decreased from 99.3+/-26.4 kg to 87.5+/-20.4 kg (z = -2.4, df = 1, p = .02), but only 7 patients lost > or = 5 kg of weight. The mean topiramate treatment dose was 492.3+/-467.8 mg/day for all 13 patients. The mean topiramate dose was higher in patients who lost > or = 5 kg than in patients who lost < 5 kg. Also, topiramate dose correlated significantly with weight loss (p < .01). In general, topiramate was well tolerated, with neurologic side effects the most common. Of 3 patients who discontinued topiramate because of side effects, 2 resumed the drug at a later date without significant recurrence of these effects.. Topiramate may be an effective treatment for binge-eating disorder. Controlled studies of topiramate in binge-eating disorder appear warranted.

Topics: Ambulatory Care; Anticonvulsants; Body Mass Index; Comorbidity; Drug Administration Schedule; Drug Therapy, Combination; Feeding and Eating Disorders; Female; Fructose; Humans; Mental Disorders; Middle Aged; Psychotropic Drugs; Research Design; Severity of Illness Index; Topiramate; Treatment Outcome; Weight Loss

The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double-blind, placebo-controlled study.. A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8-week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placebo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial.. In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a > or =50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group.. TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dizziness; Double-Blind Method; Epilepsies, Partial; Female; Fructose; Humans; Male; Middle Aged; Placebos; Topiramate; Treatment Outcome; Weight Loss

In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as add-on therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b.i.d)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced > or = 50% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75-100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentration, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefit/risk ratio of TPM in resistant partial epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Attention; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Fatigue; Female; Fructose; Headache; Humans; Male; Medical Records; Middle Aged; Paresthesia; Placebos; Topiramate; Treatment Outcome; Weight Loss

Long-term treatment of obesity with lifestyle changes alone is unsustainable for most individuals because of several factors including adherence and metabolic adaptation. Medical management of obesity has proven efficacy for up to 3 years in randomized controlled trials. However, there is a dearth of information regarding real-world outcomes beyond 3 years.. This work aimed to assess long-term weight loss outcomes over a 2.5- to 5.5-year period with US Food and Drug Administration (FDA)-approved and off-label antiobesity medications (AOMs).. A cohort of 428 patients with overweight or obesity were treated with AOMs at an academic weight management center with an initial visit between April 1, 2014, and April 1, 2016. Intervention included FDA-approved and off-label AOMs. The primary outcome was percentage weight loss from initial to final visit. Key secondary outcomes included weight reduction targets as well as demographic and clinical predictors of long-term weight loss.. The average weight loss was 10.4% at a mean follow-up duration of 4.4 years. The proportions of patients who met the weight reduction targets of 5% or greater, 10% or greater, 15% or greater, and 20% or greater were 70.8%, 48.1%, 29.9%, and 17.1%, respectively. On average, 51% of maximum weight loss was regained, while 40.2% of patients maintained their weight loss. In a multivariable regression analysis, a higher number of clinic visits was associated with more weight loss. Metformin, topiramate, and bupropion were associated with increased odds of maintaining 10% or greater weight loss.. Clinically significant long-term weight loss of 10% or more beyond 4 years is achievable in clinical practice settings with obesity pharmacotherapy.

Topics: Anti-Obesity Agents; Humans; Life Style; Obesity; Topiramate; Weight Loss

The U.S. Food and Drug Administration approved phentermine-topiramate for obesity in 2012 and required a Risk Evaluation and Mitigation Strategy (REMS) to prevent prenatal exposure. No such requirement was introduced for topiramate.. To evaluate the rate of prenatal exposure, contraceptive use, and pregnancy testing among patients with phentermine-topiramate compared with topiramate or other antiobesity medications (AOMs).. Retrospective cohort study.. Nationwide health insurance claims database.. Females aged 12 to 55 years with no infertility diagnosis or sterilization procedure. Patients with other indications for topiramate were excluded to identify a cohort that was likely treated for obesity.. Patients initiated use of phentermine-topiramate, topiramate, or an AOM (liraglutide, lorcaserin, or bupropion-naltrexone). Pregnancy at treatment initiation, conception during treatment, contraceptive use, and pregnancy testing outcomes were ascertained. Measurable confounders were adjusted for, and extensive sensitivity analyses were done.. A total of 156 280 treatment episodes were observed. Adjusted prevalence of pregnancy at treatment initiation was 0.9 versus 1.6 per 1000 episodes (prevalence ratio, 0.54 [95% CI, 0.31 to 0.95]) for phentermine-topiramate versus topiramate. The incidence rate of conception during treatment was 9.1 versus 15.0 per 1000 person-years (rate ratio, 0.61 [CI, 0.40 to 0.91]) for phentermine-topiramate versus topiramate. Both outcomes were similarly lower for phentermine-topiramate compared with AOM. Prenatal exposure was marginally lower in topiramate users compared with AOM users. Approximately 20% of patients in all cohorts had at least 50% of treatment days covered by contraceptives. Few patients had pregnancy tests before treatment (≤5%), but this was more common among phentermine-topiramate users.. Outcome misclassification; unmeasured confounding due to lack of prescriber data to account for possible clustering and spillover effects.. Prenatal exposure seemed to be significantly lower among phentermine-topiramate users under the REMS. Pregnancy testing and contraceptive use appeared to be inadequate for all groups, which deserves attention to prevent the remaining potential exposures.. None.

Topics: Anti-Obesity Agents; Contraceptive Agents; Female; Fructose; Humans; Obesity; Phentermine; Pregnancy; Prenatal Exposure Delayed Effects; Retrospective Studies; Risk Evaluation and Mitigation; Topiramate; Weight Loss

Transoral outlet reduction (TORe) and antiobesity medication (AOM) are effective treatments for weight regain after Roux-en-Y gastric bypass (RYGB). This study aims to assess the efficacy of combination therapy (TORe + AOM) for treating weight regain and to compare the safety and efficacy of combination therapy with AOM alone, TORe alone, and surgical revision of RYGB.. This was a retrospective study of RYGB patients with weight regain who underwent combination therapy, defined as initiation of at least 1 AOM within 6 months before or after TORe. Outcomes were weight loss after combination therapy and comparison of combination therapy with AOM alone, TORe alone, and surgical revision.. One hundred forty-five RYGB patients underwent combination therapy. Most commonly prescribed AOMs were topiramate, phentermine/topiramate, phentermine, and liraglutide. At 12 months, patients experienced 15.2% ± 7.4% total weight loss (TWL). Ninety percent of patients achieved ≥5% TWL at 12 months. Combination therapy was associated with greater weight loss than AOM alone (15.2% ± 7.4% vs 6.8% ± 8.2% TWL, P < .0001) or TORe alone (15.2% ± 7.4% vs 8.7% ± 8.3% TWL, P < .0001), with similar serious adverse event rates (2.1% vs 4.7% vs .6% for combination therapy vs AOM alone vs TORe alone, P > .05). Combination therapy yielded similar weight loss to surgical revision (15.2% ± 7.4% vs 16.4% ± 13.1% TWL, P = .34), with a lower serious adverse event rate (2.1% vs 14.3%, P = .0004).. Combination of TORe with AOM is superior to either therapy alone, providing similar efficacy to surgical revision with a better safety profile for the treatment of weight regain after RYGB.

Topics: Gastric Bypass; Humans; Phentermine; Reoperation; Retrospective Studies; Topiramate; Weight Gain; Weight Loss

Bariatric surgery is the most efficient treatment for obesity. However, in some cases, weight regain can occur. Currently, it is unknown the best antiobesity medication (AOM) for such clinical situation. This study aims to evaluate the effect of AOM in patients with weight regain after bariatric surgery.. A retrospective cohort study from December 2010 to July 2019 with patients submitted to bariatric surgery that had weight regain and received AOM for at least 2 years.. Of 96 patients that had weight regain in the analyzed period and received AOM, 16 were excluded from the analysis due to non-compliance (n = 7), treatment failure (n = 5), intolerable side effects with all available AOM (n = 2), or interaction with other medications (n = 2). Eighty patients were included in the analysis. The mean age was 59.0 ± 10.1 years, 88.8% were female, 91.2% white, and most of them were submitted to gastric bypass (87.6%). The mean preoperative and nadir weight after surgery were 127.9 ± 25.5 kg and 84.7 ± 22.8 kg, respectively. At the initiation of AOM, the mean baseline weight was 99.4 ± 23.1 kg. After 2 years of follow-up, there was significant weight loss in the groups treated with topiramate-alone (- 3.2 kg), topiramate plus sibutramine (- 6.1kg), and orlistat-alone or in combination (- 3.9kg). No statistical difference was observed in the sibutramine-alone group.. Topiramate (alone or associated with sibutramine) and orlistat (alone or in combination) promoted significant weight loss after 2 years of use in patients submitted to bariatric surgery with weight regain.

Topics: Aged; Anti-Obesity Agents; Bariatric Surgery; Female; Humans; Male; Middle Aged; Obesity, Morbid; Orlistat; Retrospective Studies; Topiramate; Weight Gain; Weight Loss

Randomized clinical trials have proven the efficacy and safety of Food and Drug Administration (FDA) approved anti-obesity medications (AOMs) for long-term use. It is unclear whether these outcomes can be replicated in real-world clinical practice where clinical complexities arise. The aim of this study was to evaluate the effectiveness and side effects of these medications in real-world multidisciplinary clinical practice settings.. We reviewed the electronic medical records (EMR) of patients with obesity who were prescribed an FDA-approved AOM for long-term use in academic and community multidisciplinary weight loss programs between January 2016 and January 2020.. We assessed percentage total body weight loss (%TBWL), metabolic outcomes, and side effect profile up to 24 months after AOM initiation.. The full cohort consisted of 304 patients (76% women, 95.2% White, median age of 50 years old [IQR, 39-58]). The median follow-up time was 9.1 months [IQR, 4.2-14.1] with a median number of 3 visits [IQR, 2-4]. The most prescribed medication was phentermine/topiramate extended-release (ER) (51%), followed by liraglutide (26.3%), bupropion/naltrexone sustained-release (SR) (16.5%), and lorcaserin (6.2%). %TBWL was 5.0%, 6.8%, 9.3%, 10.3%, and 10.5% at 3, 6, 12, 18, and 24 months. 60.2% of the entire cohort achieved at least 5% TBWL. Overall, phentermine/topiramate-ER had the most robust weight loss response during follow-up, with the highest %TBWL at 12 months of 12.0%. Adverse events were reported in 22.4% of patients. Only 9% of patients discontinued the medication due to side effects.. AOMs resulted in significant long-term weight loss, that was comparable to outcomes previously reported in clinical trials.

Topics: Adult; Anti-Obesity Agents; Female; Humans; Male; Middle Aged; Obesity; Phentermine; Topiramate; Weight Loss

Nearly 90% of individuals with type 2 diabetes mellitus (T2DM) are either overweight or obese, placing them at high risk of microvascular and macrovascular complications. The main objective of this study was to assess the use of antiobesity medications and antihyperglycemic agents that produce weight gain among patients with T2DM who qualify for National Institutes of Health guideline-recommended pharmacologic weight loss therapy.. Among adults with T2DM who qualified for antiobesity treatment (N = 2910), only 40 participants (2.2%; 95% CI, 1.5-3.3) were on pharmacologic antiobesity treatment within 30 days of survey interview. The only antiobesity medications identified were liraglutide (n = 34 [1.9%]), phentermine (n = 4 [0.2%]), orlistat (n = 1 [0.1%]), and phentermine/topiramate (n = 1 [0.0%]). Among those who were on antihyperglycemic treatment (n = 2401), 1661 (66%; 95% CI, 63.1-68.8) were on weight-inducing antihyperglycemic agents; however, a downward trend in the use of these agents over time was observed (from 78.4% in 2005-2006 to 53.3% in 2015-2016; P < 0.0005).. This is the first national epidemiologic study evaluating the use of antiobesity medications and weight-inducing antihyperglycemic agents among patients with T2DM who qualify for weight loss therapy. This study documents that patients are not on guideline-directed weight loss therapy. Furthermore, weight loss goals are likely compromised by 66% of individuals being on weight-inducing antihyperglycemic therapy. Use of antiobesity medications could play a significant role in promoting weight loss and potentially lead to a healthier lifestyle, which could reduce microvascular and macrovascular complications. Stronger recommendations in using guideline-directed therapy in obesity complicated by T2DM are necessary.

Topics: Adult; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Liraglutide; Nutrition Surveys; Obesity; Orlistat; Phentermine; Prevalence; Topiramate; United States; Weight Loss

Prader-Willi syndrome (PWS) is characterised by childhood-onset hyperphagia and obesity however limited data are available to guide treatment of obesity in this population. We aimed to evaluate the safety, tolerability, and efficacy of intensive medical weight loss interventions (very-low-energy diets [VLED] and/or pharmacotherapy) in individuals with PWS attending a specialist obesity management service.. A retrospective audit was undertaken of individuals with PWS attending the Austin Health Weight Control Clinic between January 2010-April 2021. Main outcome measures were weight outcomes, duration of use, and adverse effects.. Data were available for 18 patients, of whom 15 were treated with intensive weight loss interventions. Median (interquartile range, IQR) age at baseline was 20 years (19-32) with median body weight 90 kg (75-118) and BMI 37 kg/m. VLED and pharmacotherapy can achieve substantial weight loss in some individuals with PWS though non-adherence results in substantial weight regain. Adverse effects were ascribed to phentermine and topiramate, whereas liraglutide was well-tolerated in this population.

Topics: Child; Humans; Liraglutide; Obesity; Phentermine; Prader-Willi Syndrome; Retrospective Studies; Topiramate; Weight Loss

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, associated with immunoglobulin G (IgG) autoantibodies against the GluN1 subunit of the NMDAR, is one of the most common types of autoimmune encephalitis. In patients with anti-NMDAR encephalitis, movement disorders (MDs) are often frequent, mainly presenting as facial dyskinesias and stereotyped movements. The alternating clinical manifestation of limb tremor with unilateral ptosis is rare. Here, we report an interesting case of a 22-year-old woman with rapid weight loss presenting with staged dyskinesia. Interestingly, she typically showed persistent tremor of the right upper limb, which would stop when her left upper eyelid drooped uncontrollably, a phenomenon that lasted for a few seconds, followed by automatic upper eyelid lift and continued persistent tremor of the upper limb. Moreover, it was fortunate to find anti-NMDAR antibodies in her cerebrospinal fluid (CSF), which indicated the patient had anti-NMDAR encephalitis. And abnormal apparent diffusion coefficient (ADC) hyperintense signals on the left midbrain interpeduncular fossa explained this manifestation of focal neurological deficit. After the systematic administration of immunotherapy (intravenous immunoglobulin, IVIG), steroid pulse therapy, and symptomatic treatment, the initial symptoms were significantly relieved except for limb tremor. The MDs were becoming less visible for the next six months under topiramate prescriptions. Noteworthy, there are no specific MD phenotypes in anti-NMDAR encephalitis. We describe the young women with unique MDs and rapid weight loss to help us get a more comprehensive understanding of anti-NMDAR encephalitis.

Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Dyskinesias; Female; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Movement Disorders; Steroids; Topiramate; Tremor; Weight Loss

While bariatric surgery restults in significant long-term weight loss for most patients with obesity, post-surgical weight gain affects a considerable percentage of patients to varying degrees of severity. Furthermore, a small but significant percentage of patients experience inadequate post-surgical weight loss. Although many studies have examined the role of anti-obesity medications to address post-operative weight regain, an evidence-based consensus has not yet been achieved because of the heterogeneity of populations studied and the studies themselves. Observational studies in the post-bariatric surgery population consistently demonstrate the benefit of medical weight management after bariatric surgery, with most evidence highlighting liraglutide, topiramate, and phentermine/topiramate. New anti-obesity medications are anticipated to be helpful for post-surgical weight optimization given their efficacy in the non-surgical population.

Topics: Anti-Obesity Agents; Bariatric Surgery; Humans; Obesity, Morbid; Topiramate; Weight Gain; Weight Loss

Topics: Adult; Anti-Obesity Agents; Bariatric Surgery; Body Mass Index; Combined Modality Therapy; Drug Therapy, Combination; Female; Humans; Metformin; Middle Aged; Obesity, Morbid; Off-Label Use; Topiramate; Weight Loss

Increases in heart rate were seen during the clinical program for fixed-dose combination phentermine (PHEN) and topiramate (TPM), an oral medication indicated for weight management; however, the effect on cardiovascular (CV) outcomes is uncertain.. The aim of the present study was to determine the extent to which the rates of major adverse CV events (MACE) in patients using PHEN and TPM (including fixed dose) differed from the MACE rates during unexposed periods.. Retrospective cohort study.. MarketScan, US insurance billing data.. Patients aged >18 years with ≥6 months of continuous enrollment in the database before taking PHEN and/or TPM or after stopping these medications.. PHEN and TPM, taken separately and together (including fixed dose).. MACE, a composite of hospitalization for acute myocardial infarction and stroke and in-hospital CV death.. Because the outcomes are rare and the duration of medication use was brief, few events occurred. The MACE rates among current users of PHEN/TPM, fixed-dose PHEN/TPM, and PHEN were lower than those among unexposed former users. In contrast, the rate of MACE among current users of TPM was greater than among unexposed former users [incidence rate ratio: PHEN/TPM, 0.57; 95% CI, 0.19 to 1.78; fixed-PHEN/TPM, 0.24; 95% CI, 0.03 to 1.70; PHEN, 0.56; 95% CI, 0.34 to 0.91; TPM, 1.58; 95% CI, 1.33 to 1.87).. Overall, the data indicated no increased risk of MACE for current PHEN/TPM users; however, the 95% CIs for the PHEN/TPM groups were broad, indicating that the data were compatible with a wide range of possible values.

Topics: Adolescent; Adult; Anti-Obesity Agents; Drug Combinations; Female; Heart Rate; Hospitalization; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Obesity; Phentermine; Retrospective Studies; Stroke; Topiramate; Weight Loss; 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

To assess the ability of medication-assisted weight loss to prevent diabetes as a function of the baseline weighted Cardiometabolic Disease Staging (CMDS) score.. We pooled data from 3,040 overweight and obese participants in three randomized controlled trials-CONQUER, EQUIP, and SEQUEL-assessing efficacy and safety of phentermine/topiramate extended release (ER) for weight loss. In these double-blind phase III trials, overweight/obese adult patients were treated with a lifestyle intervention and randomly assigned to placebo versus once-daily oral phentermine/topiramate ER. The weighted CMDS score was calculated using baseline quantitative clinical data including waist circumference, blood glucose, blood pressure, and blood lipids. Incident diabetes was defined based on serial measures of fasting glucose, 2-h oral glucose tolerance test glucose, and/or HbA. The absolute decrease in 1-year diabetes incidence rates in subjects treated with medication versus placebo was greatest in those with high-risk CMDS scores at baseline (10.43-6.29%), intermediate in those with moderate CMDS risk (4.67-2.37%), and small in the low-risk category (1.51-0.67%). The number of participants needed to treat to prevent one new case of diabetes over a 56-week period was 24, 43, and 120 in those with baseline CMDS scores of ≥60, 30-59, and 0-29, respectively.. Numbers needed to treat to prevent one case of type 2 diabetes are markedly lower in patients with high-risk scores. CMDS can be used to quantify risk of diabetes in overweight/obese individuals and predict the effectiveness of weight-loss therapy to prevent diabetes.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Fructose; Humans; Life Style; Male; Middle Aged; Obesity; Phentermine; Topiramate; Waist Circumference; Weight Loss

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

Clinical response to topiramate can vary greatly in obese patients. Identifying genetic variants associated with treatment response could help gain insight into the mechanism of action of topiramate. Little is known about the relationship between genetic variability and topiramate treatment response. We performed a large-scale candidate-gene study to identify genetic risk factors predictive of topiramate-induced weight loss.. We collected DNA samples from patients who had previously participated in clinical trials to assess the efficacy of topiramate for the treatment of obesity. A custom chip containing single nucleotide polymorphisms from ∼ 480 candidate genes was utilized to genotype a discovery cohort of 445 obese patients from a clinical study. Variants predictive of topiramate-induced weight loss were identified and further tested in an independent replication cohort of drug-naive, obese patients with type 2 diabetes (N=139).. We identified a haplotype in INSR that may contribute to differential topiramate-induced weight loss. Carriers and noncarriers of an INSR haplotype lost 9.1 and 7.0% of body weight, respectively (P = 6.5 × 10(-6), P adj = 0.001). This finding was replicated, with carriers and noncarriers losing 9.5 and 7.3% of body weight, respectively (P Bonf=0.02), in the independent replication cohort. We also identified an SNP in HNF1A that may be associated with topiramate response and an SNP in GRIA3 that may be associated with nonpharmacologic treatment response.. According to our preliminary findings, genetic variation in the INSR and HNF1A genes may differentially affect weight loss in obese individuals treated with topiramate and genes related to insulin action are implicated in modulating topiramate response. However, these findings need to be further replicated in additional larger samples.

Topics: Adult; Anti-Obesity Agents; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Fructose; Humans; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Topiramate; Weight Loss

Bariatric surgery is an effective therapeutic option for management of obesity. However, weight recidivism (WR) and weight loss plateau (WLP) are common problems. We present our experience with the use of two pharmacotherapies in conjunction with our standard diet and exercise program in those patients who experienced WR or WLP.. From June 2010 to April 2014, bariatric surgery patients who experienced WR or WLP after undergoing Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), and who were treated with phentermine (Ph) or phentermine-topiramate (PhT), were reviewed retrospectively. Generalized estimating equations were used to compare patient weights through 90 days between initial surgery type and medication type. Patient weights, medication side effect, and co-morbidities were collected during the first 90 days of therapy.. Fifty-two patients received Ph while 13 patients received PhT. Overall, patients in both groups lost weight. Among those whose weights were recorded at 90 days, patients on Ph lost 6.35 kg (12.8% excess weight loss (EWL); 95% confidence interval (CI) 4.25, 8.44) and those prescribed PhT lost 3.81 kg (12.9% EWL; CI 1.08, 6.54). Adjusting for baseline weight, time since surgery, and visit through 90 days, patients treated with Ph weighed significantly less than those on PhT throughout the course of this study (1.35 kg lighter; 95% CI 0.17, 2.53; p = 0.025). There were no serious side effects reported.. Phentermine and phentermine-topirimate in addition to diet and exercise appear to be viable options for weight loss in post-RYGB and LAGB patients who experience WR or WLP.

Topics: Adult; Anti-Obesity Agents; Bariatric Surgery; Diet, Reducing; Exercise Therapy; Female; Fructose; Humans; Laparoscopy; Male; Middle Aged; Obesity; Phentermine; Retrospective Studies; Topiramate; Weight Loss

This study aims to see whether patients in a real-world setting taking topiramate for varied indications experience significant weight loss.. This was a retrospective cohort study from the Veterans Affairs San Diego Healthcare System. Patients were new topiramate users between January 1, 2000 and December 31, 2013 with body mass index > 25 kg/m(2) and medication possession ratio > 0.5. Primary outcome determined if topiramate users experienced significant changes in weight and body mass index. Secondary outcome analyzed predictive factors associated with 5% weight loss using logistic regression models. Patients were followed up 1 year post index date.. A total of 767 patients were included in the final analysis. Patients lost an average of 5.6 lbs (216.1 lbs preweight vs. 210.5 lbs postweight) at an average follow-up of 7.8 months. A total of 43.2% (92/213) of females lost 5% of their body weight compared to 29.4% (163/554) of males. Females (odds ratio 1.73; 95% confidence interval 1.21-2.48; p = 0.003), topiramate indication other than headache, and adherent patients (odds ratio 1.78; 95% confidence interval 1.28-2.49; p = 0.001) were more likely to lose 5% of body weight.. Topiramate should be considered with higher priority in overweight and obese patients for nonweight loss indications for dual benefit.

Topics: Adult; Aged; Anti-Obesity Agents; Anticonvulsants; Body Mass Index; Female; Fructose; Humans; Male; Middle Aged; Obesity; Retrospective Studies; Topiramate; United States; United States Department of Veterans Affairs; Veterans; 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

To monitor weight regain after therapy discontinuation in patients with migraine experiencing weight loss during topiramate (TPM) treatment.. Patients with migraine without aura were enrolled in this observational prospective study. Weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, and ghrelin, and homeostatic model assessment of insulin resistance (HOMA-IR) were evaluated before starting TPM (T1), at 3 (T2) and 6 (T3) months of treatment and 6 months after withdrawal of TPM (T4). Weight loss/regain was considered as a change of 5% of pre-TPM body weight.. A total of 241 patients were analyzed. Of these, 87 (36%) patients experienced weight loss on TPM medication. During TPM therapy significant reductions in mean values of weight (p<0.001), BMI (p<0.001), waist circumference (p<0.01), HOMA-IR (p<0.01), and leptin (p<0.01) were observed. After TPM discontinuation, all of these parameters showed a clear trend to increase at T4, achieving pre-TPM values in 27 patients. Among potential predictors, only HOMA-IR before starting TPM (parameter estimate=1.36, effect size=0.75; p=0.006) was significantly associated with weight regain after therapy discontinuation.. Loss of body weight is a reversible effect, which at 6 months after TPM discontinuation shows a clear trend to return to baseline values. HOMA-IR is the only predictive factor of weight regain.

Topics: Adult; Body Mass Index; Central Nervous System Agents; Cholesterol; Female; Fructose; Humans; Insulin Resistance; Linear Models; Male; Migraine without Aura; Prognosis; Prospective Studies; Severity of Illness Index; Topiramate; Waist Circumference; Weight Gain; Weight Loss; Young Adult

Topics: Anti-Obesity Agents; Autism Spectrum Disorder; Female; Fructose; Humans; Topiramate; Weight Loss; Young Adult

In 2012, the US Food and Drug Administration approved 2 drugs for long-term weight loss: lorcaserin hydrochloride (Belviq; Eisai Inc) and phentermine-topiramate (Qysmia; Vivus Inc). The approvals were based on 1-year trials showing that on top of recommendations to follow a calorie-restricted diet and to increase exercise, patients randomized to either drug lost more weight than patients randomized to placebo (3% [95% CI, 3%-4%] more weight lost with lorcaserin; 7% [95% CI, 3%-4%] more with phentermine /topiramate). The drugs have been associated with serious harms: Both drugs' labels include warnings about memory, attention, or language problems and depression; for lorcaserin, the label also warns of valvular heart disease and euphoria; and for phentermine-topiramate, the label warns of metabolic acidosis, increased heart rate, anxiety, insomnia, and elevated creatinine levels. Neither medication is marketed in Europe because of safety concerns. The manufacturer withdrew its application for lorcaserin in Europe after the European Medicines Agency (EMA) said approval was unlikely, and the EMA rejected phentermine-topiramate. In the United States, the required postmarketing safety trials are behind schedule. Until there is more convincing evidence about the cardiovascular safety of these drugs, physicians and patients should approach them cautiously. Patients who do not lose at least 5% of their body weight within 12 weeks of starting to take either drug should stop taking it, as stated in the prescribing information.

Topics: Anti-Obesity Agents; Benzazepines; Female; Fructose; Humans; Male; Obesity; Phentermine; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Topiramate; United States; United States Food and Drug Administration; Weight Loss

To investigate the safety, tolerability and efficacy of combination phentermine and topiramate therapy for maintenance of weight loss.. Retrospective audit of patients attending the Austin Health Weight Control Clinic who were dispensed phentermine-topiramate between 22 January 2010 and 16 July 2012 and after reaching a target weight by following a very low energy diet (VLED). Data collection continued until July 2013.. Number of patients who ceased pharmacotherapy; duration of use of pharmacotherapy; types and numbers of adverse effects; and mean weight and blood pressure measurements at the initial visit, the end of the VLED and the last observation during pharmacotherapy.. Data were available for 103 patients who were dispensed phentermine-topiramate; 61 patients ceased combination pharmacotherapy before the end of the data collection period, 41 due to adverse effects (eg, paraesthesia, cognitive changes, dry mouth and depression). The mean duration of use of pharmacotherapy was 10 months. Mean weight decreased by 10% due to the VLED (from 135.5 kg to 122.5 kg) and this loss was maintained. For 30 patients who continued on phentermine-topiramate, the mean duration of pharmacotherapy was 22 months and the mean weight decreased by 6.7 kg between the end of the VLED and the last observation during pharmacotherapy.. Phentermine-topiramate therapy was not well tolerated; more than half of the patients in our study stopped taking it because of adverse effects, and more than half of the adverse events reported were ascribed to topiramate. However, in those able to continue with pharmacotherapy, the combination was efficacious for both maintenance of weight loss and ongoing weight loss.

Topics: Anti-Obesity Agents; Australia; Body Mass Index; Drug Therapy, Combination; Follow-Up Studies; Fructose; Humans; Medical Audit; Obesity; Phentermine; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Topiramate; Treatment Failure; Treatment Outcome; Weight Loss

Topics: Benzazepines; Bupropion; Drug Combinations; Drug Prescriptions; Fructose; Humans; Naltrexone; Obesity; Phentermine; Topiramate; Weight Loss

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

Topics: Appetite Depressants; Benzazepines; Drug Utilization; Fructose; Humans; Obesity; Phentermine; Prescription Drugs; Topiramate; United States; Weight Loss

Topics: Anti-Obesity Agents; Female; Follow-Up Studies; Fructose; Humans; Middle Aged; Migraine Disorders; Neuroprotective Agents; Obesity, Morbid; Topiramate; Treatment Outcome; Weight Loss

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Cyclobutanes; Fructose; Humans; Naltrexone; Obesity; Phentermine; Risk Assessment; Risk Factors; Topiramate; Weight Loss

Topics: Adult; Anti-Obesity Agents; Benzazepines; Dose-Response Relationship, Drug; Drug Combinations; Drugs, Investigational; Female; Fructose; Heart Valve Diseases; Humans; Male; Obesity; Phentermine; Pregnancy; Tachycardia; Teratogens; Topiramate; Weight Loss

In France, extra restrictions have been placed on this appetite-suppressant drug. Phentermine is widely used in many countries despite its multiple adverse effects and lack of proven efficacy in preventing complications of obesity.

Topics: Anti-Obesity Agents; Appetite Depressants; Appetite Regulation; Drug and Narcotic Control; Drug Combinations; Evidence-Based Medicine; France; Fructose; Humans; Narcotics; Obesity; Phentermine; Topiramate; Treatment Outcome; Weight Loss

Topics: Abnormalities, Drug-Induced; Anti-Obesity Agents; Benzazepines; Delayed-Action Preparations; Drug Approval; Drug Combinations; Female; Fructose; Humans; Obesity; Phentermine; Pregnancy; Serotonin Receptor Agonists; Topiramate; United States; United States Food and Drug Administration; Weight Loss

Topics: Anti-Obesity Agents; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Combinations; Fructose; Humans; Life Style; Obesity; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; Weight Loss

Topics: Anti-Obesity Agents; Drug Combinations; Fructose; Heart Valve Diseases; Humans; Obesity; Phentermine; Topiramate; Weight Loss

Topics: Anti-Obesity Agents; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Topiramate; United States; United States Food and Drug Administration; Weight Loss

Topiramate is newly approved as anticonvulsant that seems to promote body weight loss in humans. The present study was designed to evaluate the weight-controlling properties of topiramate in dietary obese female rats in comparison with sibutramine.. Fifty rats were assigned as normal, high fat diet (HFD), HFD + sibutramine (7.5 mg/kg, p.o.), HFD + topiramate (25 mg/kg, p.o.) and HFD + topiramate (50 mg/kg, p.o.). Body weight was registered, anxiety was tested in Vogel's test and blood pressure (BP) was measured. In addition, liver index, adipose tissue index, fasting blood glucose and serum lipid profile were measured in all groups. Further, serum insulin, leptin and adiponectin were determined.. Feeding with HFD induced a significant increase in body weight of rats as well as insulin resistance and serum lipids as compared to normal group (p<0.05). These measurements were suppressed by sibutramine treatment. However, a significant elevation in BP and anxiety behavior were detected as compared with HFD group (p<0.05). Topiramate (50 mg/kg, p.o.) group showed weight loss, improved insulin resistance, lessened anxiety behavior without influence on BP.. Our data ensures the findings that topiramate has a weight controlling properties with no anxiogenic or hypertensive effects. Further investigations are needed to determine the utility of topiramate in the clinical management of obesity.

Topics: Animals; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Cyclobutanes; Female; Fructose; Insulin; Insulin Resistance; Leptin; Lipids; Obesity; Rats; Topiramate; Weight Loss

Qnexa (VI-0521) is an investigational fixed-dose combination drug of phentermine and topiramate currently in Phase III clinical trials for the treatment of obesity. Vivus, Inc. has demonstrated efficacy of their product and are currently addressing FDA safety concerns with the possibility of a New Drug Application (NDA) resubmission.

Topics: Anti-Obesity Agents; Appetite Depressants; Clinical Trials, Phase III as Topic; Comorbidity; Double-Blind Method; Drug Approval; Drug Combinations; Fructose; Humans; Obesity; Overweight; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; United States; United States Food and Drug Administration; Weight Loss

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 metabolic and endocrine parameters in patients with migraine independently of any intention to lose body weight. Six patients (26-61 years old, body mass indices [BMI] 20.9-32.1 kg/m(2)) with migraine were treated with an average dose of 100 mg topiramate/day over a period of 20 weeks. The following parameters were measured every 4-8 weeks: BMI, body fat proportion, waist and hip circumference, HOMA insulin resistance, fasting serum-/plasma concentrations of adiponectin, leptin, ghrelin, vascular endothelial growth factor (VEGF), cortisol, interleukin-6 and tumor necrosis factor (TNF)-alpha. Profound metabolic changes were observed for the whole treatment period. Compared with the baseline value, 20 weeks of treatment reduced the BMI by 7.2+/-1.4%, body fat proportion by 11.6+/-3.6%, waist circumference by 4.2+/-1.2%, leptin by 39.2+/-6.5% and HOMA insulin resistance by 37.3+/-5%, while adiponectin was increased by 69.9+/-17.3% (P<0.05, respectively). VEGF concentrations increased during the week 2-4 by 177.4+/-39.4% (P<0.05) followed by a continuous decrease. There were trends for a reduction in ghrelin concentration, whereas cortisol, interleukin-6 and TNF-alpha values were unchanged. In summary, in this small sample of migraine patients topiramate treatment was associated with increased insulin sensitivity, increased adiponectin concentration and a reduction of body fat in all treated patients. The role of increased VEGF concentrations prior to these metabolic changes is not clear and might, hypothetically, involve a centrally mediated effect of topiramate on body weight regulation.

Topics: Adiponectin; Adipose Tissue; Adult; Anti-Obesity Agents; Anticonvulsants; Body Mass Index; Cytokines; Female; Fructose; Hip; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Vascular Endothelial Growth Factors; Waist Circumference; Weight Loss

Topiramate (TPM) is generally recognized efficacious and safe in migraine prevention. A significant proportion of patients undergoing TPM administration may show weight loss. In epileptic subjects, high body mass index (BMI) was found to be predictive of weight loss under TPM therapy. We therefore aimed to study whether common clinical determinants may be associated to TPM weigh loss in migraine patients. In our clinical series, high BMI was not found a predictor of weight loss under TPM treatment. Unknown genetic and environmental factors that may determine the courses of weight loss under TPM therapy are still do be identified.

Topics: Adult; Body Mass Index; Female; Fructose; Humans; Linear Models; Male; Migraine Disorders; Prospective Studies; Topiramate; Weight Loss

To evaluate prospectively the relationship between appetite, food composition, nutritional habits and weight loss following administration of topiramate (TPM) and to identify predictors for TPM induced weight loss.. 22 patients with epilepsy who were started on TPM were prospectively followed for 6 months and contacted again after a mean follow-up time of 37.1 months.. Body mass index (BMI) loss occurred in 59% of patients, with a mean weight loss of 9.5 kg after 6 months while receiving TPM without further weight loss at the long term follow-up. Weight loss was associated with reduction in appetite without affecting food composition. Predictors for BMI loss after 6 months were high initial BMI and body fat. After 3 weeks of treatment with TPM, the recorded parameters did not predict BMI loss but at 3 months, weight loss, reduction of appetite and amount of food intake were predictive for the amount of BMI loss after 6 months.

Topics: Adult; Anticonvulsants; Appetite; Body Mass Index; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Feeding Behavior; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Nutritional Status; Prospective Studies; Topiramate; Weight Loss

Topiramate is a new broad-spectrum anti-epileptic drug. Decreased body weight and appetite are common side effects of topiramate. The side effect affects the growth and development in children greatly. Little is known about the mechanisms of topiramate-induced weight loss and decreased appetite in children with epilepsy in China and abroad. galanin is one of factors that affect appetite. It is a neuroendocrine peptide and play an important role in the control of appetite and body weight in the mechanism of hormone release. The purpose of this study was to explore the mechanism of topiramate-induced weight loss in children with epilepsy and the relation of weight loss with change of galanin, thereby to provide evidences for improvement of quality of life, compliance to treatment and reduce side effects of growth and development in children with epilepsy.. Totally 61 patients with especial epilepsy were enrolled into this study and the disease was defined by clinical manifestations and electroencephalography (EEG). Among them 32 cases had generalized seizures and 29 had local seizures. Sixteen normal children were enrolled as control group. The patients' age ranged from 0.5 to 14 (4.76 +/- 4.05) years and the patients were instructed to take 0.5 - 1 mg/kg of topiramate per day, with 0.5 - 1 mg/kg every 3 - 5 d increased to maximum of 3 - 8 mg/kg per day. Patients continued receiving the doses for 4 months. All patients' serum galanin levels and body height and weight and hepatic function were detected before and after antiepileptic drugs treatment. The galanin was detected by using radioimmunoassay.. After treatment with topiramate (61 cases) for 4 months, plasma galanin [(22.01 +/- 8.12) pg/ml] declined as compared with baseline [(26.56 +/- 9.35) pg/ml, t = 2.85, P < 0.01] in children with epilepsy. Twenty-two of 61 patients lost weight, their plasma galanin concentration was significantly lower [(26.51 +/- 10.00) pg/ml vs. (20.45 +/- 8.09) pg/ml, t = 2.91, P < 0.01], but there was no significant change in the weight-gained patients (39/61) and control group (n = 16). In children with epilepsy, the mean value of body weight decreased as compared with the pre-treatment values, but the difference was not significant; however, the body-mass index (BMI) was significantly lower than that obtained before treatment (t = 8.628, P < 0.01). Eighteen of 22 patients who lost weight had decreased appetite, but only five of 39 patients who gained weight showed decreased appetite (chi(2) = 28.50, P < 0.001). The mean value of plasma galanin declined after treatment in patients (23 cases) with decreased appetite [(18.35 +/- 7.80) pg/ml vs. (27.28 +/- 6.90) pg/ml, t = 4.84, P < 0.001]; while plasma galanin did not change significantly after treatment in patients (38 cases) without decreased appetite [(24.23 +/- 7.66) pg/ml vs. (26.12 +/- 5.49) pg/ml, t = 1.04, P > 0.05].. Topiramate treatment may lower the body weight and reduce appetite in part of children with epilepsy which may be mediated by the reduced plasma galanin level.

Topics: Adolescent; Anticonvulsants; Appetite; Case-Control Studies; Child; Child, Preschool; Epilepsy; Female; Fructose; Galanin; Humans; Infant; Male; Topiramate; Weight Loss

Atypical antipsychotics have been associated with weight gain. This study examines the efficacy of adjunctive topiramate in patients with schizophrenia and schizoaffective disorder with antipsychotic-induced weight gain.. A 2-year retrospective case analysis was performed in all 300 patients of the outpatient Special Follow-up Clinic for chronic schizophrenia and related psychoses at the Allan Memorial Institute, McGill University Health Centre (Montreal, Canada), a tertiary care University teaching hospital.. 10 patients met study inclusion criteria. Mean daily topiramate dose was 197.5 mg (A+/-77) (range, 125-400 mg). Topiramate produced continued weight loss throughout the study duration without tolerance. Patients treated for 6 months and more had significantly higher Body Mass Index (BMI) differences than those treated for shorter durations (BMI-d6 months=-4.7A+/-2.4; BMI-d2 months=-3.2A+/-2.3; P=0.015). BMI changes were similar across genders.. This study supports topiramate use to target weight loss in stable overweight schizophrenic patients as a potential therapy that requires further investigation.

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Body Mass Index; Female; Fructose; Humans; Male; Ontario; Overweight; Retrospective Studies; Schizophrenia; Topiramate; Weight Loss

Topics: Anorexia; Anti-Obesity Agents; Appetite; Conditioning, Psychological; Energy Intake; Energy Metabolism; Fructose; Humans; Male; Topiramate; Weight Loss

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

To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder.. In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of > or =1 previous manic or mixed episodes, and > or =20 Young Mania Rating Scale (YMRS) score were randomized to double-blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9-week double-blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study.. Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, -5.1 to -8.4). Mean YMRS reductions in lithium-treated groups were significantly greater (p < or = 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo.. These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression. Lithium was confirmed as an effective therapy in this population.

Topics: Acute Disease; Adolescent; Adult; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Double-Blind Method; Female; Fructose; Humans; Lithium; Male; Middle Aged; Multicenter Studies as Topic; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; Weight Loss

Topics: Amino Acids, Branched-Chain; Anti-Obesity Agents; Dyskinesia, Drug-Induced; Fructose; Humans; Male; Middle Aged; Schizophrenia, Paranoid; Selective Serotonin Reuptake Inhibitors; Time Factors; Topiramate; Weight Loss

To review the adverse drug reactions (ADRs) of Topiramate and Lamotrigine among children in Israel, and to compare the two drugs, based on their side effect profile and tolerability among this population.. We performed a cross-sectional study. Four paediatric neurologists from three different tertiary medical centres in Israel documented all cases of children from birth to the age 18 years, treated with Topiramate and/or Lamotrigine in their respective outpatient clinics and hospital wards. All present ADRs and their characteristics were recorded.. Reports on 45 and 65 children treated with Topiramate and Lamotrigine respectively, were received. Half of the children treated with Topiramate suffered from one or more ADRs, as opposed to one-third of the children treated with Lamotrigine (p = 0.03). Most reactions were considered mild to moderate. There were no deaths or hospitalisations, but the drug had to be discontinued in about 10% of the patients due to ADRs. Most Topiramate and Lamotrigine ADRs appeared early in the treatment and were more frequent when Topiramate was an add-on versus a monotherapy drug. Most ADRs of both Topiramate and Lamotrigine were related to the central nervous system; while poor appetite, drowsiness, speech difficulties and weight loss were observed only with Topiramate, and rash and headaches only with Lamotrigine. Nervousness and seizure aggravation were more frequent ADRs of Topiramate whereas sleep disturbances were observed more in children treated with Lamotrigine.. Results of this study indicate that Lamotrigine causes ADRs less frequently than Topiramate; however both medications are generally well tolerated. Topiramate and Lamotrigine differ in their central nervous system side effect profile.

Topics: Adolescent; Adverse Drug Reaction Reporting Systems; Anticonvulsants; Child; Child, Preschool; Cross-Sectional Studies; Drug Monitoring; Drug Therapy, Combination; Fatigue; Feeding and Eating Disorders; Female; Fructose; Humans; Infant; Lamotrigine; Multicenter Studies as Topic; Sleep Stages; Time Factors; Topiramate; Treatment Outcome; Triazines; Weight Loss

Topiramate is the second antiepileptic drug, after valproate, to be approved by the FDA for prevention of migraine. There is no evidence that it is more effective than a beta-blocker for this indication, and it is much more expensive. Topiramate can cause cognitive impairment and weight loss. No studies have compared it to valproate for this indication.

Topics: Anticonvulsants; Cognition Disorders; Fructose; Humans; Migraine Disorders; Topiramate; Weight Loss

To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy.. Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (> or =5% incidence) AEs were calculated for patients completing the 12-week study.. The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits.. This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Anxiety; Carbamazepine; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Feeding and Eating Disorders; Female; Fructose; Headache; Humans; Incidence; Male; Meta-Analysis as Topic; Middle Aged; Paresthesia; Placebos; Randomized Controlled Trials as Topic; Sleep Wake Disorders; Time Factors; Topiramate; Weight Loss

Topics: Adult; Anticonvulsants; Epilepsy; Female; Fructose; Humans; Male; Topiramate; Weight Loss

Metabolic syndrome has been recognised as a cluster of risk factors contributing to the development of cardiovascular diseases. Different diagnostic criteria have been proposed and the consensus focuses on four major risk factors: obesity, diabetes, dyslipidaemia and hypertension. Although treatment options are available to treat each component separately, a highly effective agent for metabolic syndrome has yet to be developed. To explore the clinical definition of metabolic syndrome and potential molecular targets that can be modulated for treatment purpose, a meeting entitled 'Targeting Metabolic Syndrome' was organised in 2004 by IBC USA Conferences, Inc. This article highlights discussions related to the clinical correlates and pathophysiology of metabolic syndrome, and reviews some of the promising drug discovery efforts. Metabolic syndrome should be treatable and preventable if obesity and insulin resistance are well controlled. New regulatory guidelines need to be developed as new treatment options are being investigated. From a broad spectrum of potential mechanisms encompassing central nervous system targets and peripheral targets for pharmacological intervention, a few promising molecular targets have emerged. Modulating these is expected to treat at least some components of metabolic syndrome.

Topics: Animals; Callithrix; Diabetes Mellitus, Experimental; Disease Models, Animal; Fructose; Humans; Hyperlipidemias; Hypertension; Macaca mulatta; Metabolic Syndrome; Mice; Obesity; Topiramate; Weight Loss

Rett syndrome, a neurodevelopmental disorder, manifests in the first few years of life with developmental arrest, stereotyped behaviors, and respiratory abnormalities. Seizures occur in 70 to 80% of patients. Clinical drug trials have not demonstrated the superiority of any specific antiepilepsy drug. We report our experience with topiramate in eight patients with Rett syndrome. Topiramate was initiated as monotherapy in two patients and as adjunctive therapy in six patients. Seven patients had improved seizure control. Respiratory abnormalities improved by 50 to 75% in two patients and by 20 to 50% in two others. In our cohort, seven of eight patients showed improvement in seizure control and/or respiratory abnormalities on topiramate. Topiramate was well tolerated. The effect of topiramate, a broad-spectrum drug, could be due to its gamma-aminobutyric acid (GABA)ergic and glutaminergic effects, both systems thought to be disordered in Rett syndrome.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Fructose; Humans; Respiration Disorders; Retrospective Studies; Rett Syndrome; Seizures; Topiramate; Weight Loss

Topiramate is currently used in the treatment of epilepsy, but this anticonvulsant drug has also been reported to exert mood-stabilizing effects and induce weight loss in patients. Neuropeptide Y (NPY) is abundantly and widely distributed in the mammalian central nervous system and centrally administered NPY markedly reduces pharmacologically induced seizures and induces antidepressant-like activity as well as feeding behavior. Two other peptides, galanin and corticotropin-releasing hormone (CRH), have also been proposed to play a modulatory role in mood, appetite, and seizure regulation. Consequently, we investigated the effects of single and repeated topiramate (10 days, once daily: 40 mg/kg i.p.) or vehicle treatment in 'depressed' flinders sensitive line (FSL) and control Flinders resistant line (FRL) rats on brain regional peptide concentrations of NPY, galanin, and CRH. The handling associated with repeated injections reduced hippocampal levels of NPY- and galanin-like immunoreactivities (LI) while NPY- and CRH-LI levels were increased in the hypothalamus, regardless of strain or treatment. In the hippocampus, concentrations of NPY-LI, galanin-LI, and CRH-LI were lower in FSL than FRL animals. Repeated topiramate treatment selectively normalized NPY-LI in this region in the FSL animals. In the hypothalamus, galanin-LI was reduced in FSL compared to FRL animals. Topiramate elevated the hypothalamic concentrations of NPY-LI, CRH-LI, and galanin-LI in both strains. Furthermore, topiramate elevated serum leptin but not corticosterone levels. The present findings show that topiramate has distinct effects on abnormal hippocampal levels of NPY, with possible implications for its anticonvulsant and mood-stabilizing effects. Furthermore, stimulating hypothalamic NPY-LI, CRH-LI and galanin-LI as well as serum leptin levels may be associated with the weight loss-inducing effects of topiramate.

Topics: Affect; Animals; Anticonvulsants; Corpus Striatum; Corticosterone; Corticotropin-Releasing Hormone; Depression; Disease Models, Animal; Drug Administration Schedule; Frontal Lobe; Fructose; Galanin; Hippocampus; Hypothalamus; Leptin; Male; Neuropeptide Y; Occipital Lobe; Radioimmunoassay; Rats; Rats, Inbred Strains; Species Specificity; Topiramate; Weight Loss

To characterize weight changes in patients with neurodevelopmental disabilities who received topiramate.. Retrospective, observational study.. State-supported developmental center.. Fifteen patients with neurodevelopmental disabilities who received topiramate therapy. Monthly weights for 1 year after the start of topiramate therapy were recorded. Mean body weight at drug initiation differed significantly compared with the nadir weight during the next 12 months (52.2+/-7.5 vs 49.9+/-7.2 kg, p<0.02). Twelve patients who were receiving ad libitum oral diets demonstrated a significant decrease in body weight (52.1+/-7.5 vs 49.0+/-7.3 kg, p<0.01), whereas the three patients who received enteral nutrition through enterostomy did not experience significant weight loss.. Weight loss is common in patients with neurodevelopmental disabilities who receive topiramate. Since patients who received oral diets lost weight whereas those receiving enteral nutrition did not, decreased nutrient intake is the likely cause of weight loss.

Topics: Adult; Enteral Nutrition; Female; Fructose; Humans; Male; Middle Aged; Nervous System Diseases; Retrospective Studies; Seizures; Statistics, Nonparametric; Topiramate; Weight Loss

Topics: Adult; Anorexia Nervosa; Anticonvulsants; Female; Fructose; Humans; Topiramate; Weight Loss

The purpose of this study was to evaluate the efficacy of topiramate in the treatment of acute manic symptoms. Fourteen patients, admitted with an acute manic episode, were treated with topiramate. All required supplementation therapy with benzodiazepines. Nine patients received topiramate as monotherapy; four of them required zuclopenthixol acutard 100 mg/48 h intramuscularly (im) for not more than 6 days. In three treatment-resistant patients, topiramate was added to the existing therapy. Finally, in two patients topiramate was coadministered with an antipsychotic from the beginning. Patients were assessed every week for 4 weeks with the Bech and Rafaelsen Mania Scale (BRMS). Mean BRMS scores declined from 26.2 to 11.6 in the fourth week (P<.001); a significant decline (P<.001) was observed after the first week. Response rate (> or = 50% reduction of BRMS) was 61.5% (8 out of 13 patients). All patients tolerated topiramate well. Reduced appetite and weight loss was observed in four patients; however, two patients presented weight gain. These preliminary findings provide support for a modest efficacy of topiramate, especially as monotherapy, in the treatment of acute mania.

Topics: Acute Disease; Adult; Aged; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clopenthixol; Female; Fructose; Hospitalization; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Topiramate; Weight Loss

To assess topiramate's efficacy and tolerability in a group of obese binge eaters with no neuropsychiatric comorbidity.. We consecutively selected 8 obese patients with binge eating disorder (BED) and no medical or psychiatric comorbidity from individuals seeking treatment for obesity. Treatment with topiramate at 150 mg daily was administered over a 16-week period. To assess outcome, we employed the days with binge episodes per week (DBE), the Binge Eating Scale (BES), the Beck Depression Inventory (BDI), and body weight evaluation.. Of the 6 patients who completed the trial, all showed reduced binge eating. Four patients presented a total remission, and 2 had a marked reduction in binge eating frequency. The mean DBE decreased significantly from 4.3 to 1.1 (P = 0.03), as did the BES scores, which fell from 31.8 to 15.3 (P = 0.04). Moreover, there was a statistically significant weight loss (mean 4.1 kg, P = 0.04). The most frequent side effects were paresthesias, fatigue, and somnolence.. Topiramate may be an effective and well-tolerated agent in the treatment of BED in obese patients.

Topics: Adult; Anti-Obesity Agents; Bulimia; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fructose; Humans; Male; Obesity; Personality Inventory; Topiramate; Treatment Outcome; Weight Loss

Topics: Adult; Antidepressive Agents, Second-Generation; Appetite; Depressive Disorder; Drug Therapy, Combination; Female; Fluoxetine; Fructose; Humans; Neuroprotective Agents; Obesity; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Topiramate; Weight Loss

Topiramate is an antiepileptic agent, which is being investigated as a mood-stabilizer. Three obese individuals with DSM-IV bipolar I disorder and type II diabetes mellitus received topiramate treatment in combination with antipsychotics and valproate or carbamazepine. In addition to improved mood stability, these individuals lost between 16 to 20.5% of their pre-topiramate body weight and also achieved significant glycemic control.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Body Mass Index; Diabetes Mellitus, Type 2; Female; Fructose; Humans; Hyperglycemia; Male; Middle Aged; Obesity; Time; Topiramate; Weight Loss

Topics: Adult; Anticonvulsants; Female; Fructose; Humans; Psychotic Disorders; Topiramate; Weight Loss

Topics: Adolescent; Anti-Obesity Agents; Antipsychotic Agents; Child; Child, Preschool; Female; Fructose; Humans; Obesity; Topiramate; Weight Loss

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

Topics: Adult; Aged; Anticonvulsants; Antidepressive Agents; Bipolar Disorder; Data Collection; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Medical Records; Middle Aged; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome; Weight Loss

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

To report a case of weight loss and mood stabilization in a patient being treated with the antiepileptic drug topiramate.. A 37-year-old obese white woman with affective instability and obesity was being treated with adjunctive topiramate therapy. The patient lost 10 kg over 10 weeks of treatment with topiramate and improved clinically, as evidenced by a reduction in the number of times that she had to be admitted to a management unit for constant observation, and a decrease in the number of times that mechanical restraints or medication interventions were required for aggressive outbursts. Furthermore, the patient successfully completed two home visits while receiving topiramate therapy and was out of the hospital on her third home visit at the time of this writing.. This case further strengthens previous reports that topiramate may be useful in treating affective disorders as well as inducing weight loss in a patient population in which weight gain is common. The patient discussed in this case report had no acute illnesses or changes in health status, no changes in diet, and no changes in her medications that could have accounted for the sudden weight loss. In addition, the patient's behavior did not improve until topiramate was added as adjunctive therapy of valproic acid, citalopram, and chlorpromazine during an adequate trial period.. Controlled studies need to be performed to evaluate the use of topiramate in the psychiatric population and, in particular, the benefits of topiramate therapy in psychiatric patients with an additional diagnosis of obesity.

Topics: Adult; Affect; Anticonvulsants; Female; Fructose; Humans; Mood Disorders; Obesity; Topiramate; Weight Loss