topiramate and Obesity

To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight.. We performed a systematic review of drugs approved for treating obesity and overweight. We searched MEDLINE, Embase and CENTRAL through 26 February 2023. Random-effects network meta-analysis was applied.. A total of 168 trials (97 938 patients) were included. There was no evidence that drugs approved for weight management had different associations with cardiovascular death (69 trials, 59 037 participants). Naltrexone/bupropion was associated with lower cardiovascular mortality than placebo (odds ratio [OR], 0.62 [95% CI: 0.39, 0.99]; low certainty evidence). All drugs were associated with greater weight loss at 12 months than placebo (33 trials, 37 616 participants), mainly semaglutide (mean difference [MD], -9.02 kg [95% CI: -10.42, -7.63]; moderate certainty) and phentermine/topiramate (MD, -8.10 kg [95% CI: -10.14, -6.05]; high certainty); and with greater waist circumference reduction at 12 months than placebo (24 trials, 35 733 participants), mainly semaglutide (MD, -7.84 cm [95% CI: -9.34, -6.34]; moderate certainty) and phentermine/topiramate (MD, -6.20 cm [95% CI: -7.46, -4.94]; high certainty). Semaglutide and phentermine/topiramate were associated with lower or no difference in the odds of treatment withdrawal compared with all other drugs (87 trials, 70 860 participants).. Among adults with obesity or overweight, semaglutide and phentermine/topiramate were associated with greater body weight loss and waist circumference reduction at 12 months than all other drugs, and lower or no significant difference in risks of withdrawal. There was no evidence that drugs approved for weight management had different associations with cardiovascular death.

Topics: Adult; Humans; Network Meta-Analysis; Obesity; Overweight; Phentermine; Randomized Controlled Trials as Topic; Topiramate

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

Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs).. While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed.. The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications.

Topics: Anti-Obesity Agents; Bupropion; Drug Therapy, Combination; Humans; Liraglutide; Liver Cirrhosis; Liver Transplantation; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate; Translational Science, Biomedical

Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well-established diagnostic criteria and significant impacts on quality of life. Clinical observations, epidemiologic evidence, and animal models of disease have strongly suggested MetS is associated with an elevated risk for cryptogenic sensory peripheral neuropathy (CSPN). MetS neuropathy preferentially affects small unmyelinated axons early in its course, and it may also affect autonomic and large fibers. CSPN risk is linked to MetS and several of its components including obesity, dyslipidemia, and prediabetes. MetS also increases neuropathy risk in patients with established type 1 and type 2 diabetes. In this review we present animal data regarding the role of inflammation and dyslipidemia in MetS neuropathy pathogenesis. Several studies suggest exercise-based lifestyle modification is a promising treatment approach for MetS neuropathy.

Topics: Bariatric Surgery; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diet Therapy; Disease Progression; Dyslipidemias; Exercise; Humans; Hypoglycemic Agents; Metabolic Syndrome; Obesity; Peripheral Nervous System Diseases; Prediabetic State; Risk Factors; Small Fiber Neuropathy; Topiramate

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

Binge eating disorder (BED) is the most common eating disorder and was newly recognized in 2013 in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). BED is frequently associated with obesity and the metabolic syndrome, as well as with other psychiatric diseases, such as mood (49%), anxiety (41%), and substance use (22%) disorders. BED is highly prevalent and carries a high burden of mental and physical illness and disability. However, BED is frequently under-recognized and under-treated.. This paper reviews the main pharmacological treatments for BED and provides an expert opinion based on the available evidence and on the authors' clinical experience with patients affected by BED.. Several medications have proven to be effective for the treatment of BED, including Lisdexamfetamine (LDX), topiramate as well as anti-anxiety and antidepressant medications. To date, LDX is the only FDA approved medication for BED. Consequently, as a general rule, the use of an FDA approved medication should always be preferred. However, when in the presence of concomitant psychiatric conditions such as anxiety or depression, other medications that have proven efficacy in those comorbid conditions can be used and may contextually provide a benefit for BED.

Topics: Antidepressive Agents; Binge-Eating Disorder; Humans; Lisdexamfetamine Dimesylate; Obesity; Topiramate

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

Few studies on combination therapies for the treatment of obesity had been conducted until recently, when two fixed-dose combinations, bupropion-naltrexone ER fixed-dose combination and phentermine-topiramate ER titrated-dose combinations were evaluated in clinical studies that ultimately led to FDA approval. Areas covered: In this review, we discuss safety concerns about both combinations, the rationale and history of combination therapies for obesity (including phentermine plus fenfluramine), and possible future new combinations. Expert opinion: Combination therapies are a promising new area in obesity treatment, similar to what occurs with diabetes and hypertension. Safety assessment is highly important due to the high number of potential users on a chronic basis.

Topics: Animals; Anti-Obesity Agents; Bupropion; Delayed-Action Preparations; Drug Combinations; Fructose; Humans; Naltrexone; Obesity; Phentermine; Topiramate

Obesity management requires a multidisciplinary approach, as there are many factors that contribute to the development of obesity, as well as the preservation of excess weight once it has been gained. Diet, exercise, and behavior modification are key components of treatment. In addition to lifestyle changes, weight gain secondary to medications is an important modifiable risk factor. Even after appropriate lifestyle modification, and medication adjustments (where possible) to avoid agents that can contribute to weight gain, many patients are still unable to achieve clinically meaningful weight loss. Pharmacotherapy for obesity management can fill an important role for these patients. This article will review medications that can lead to weight gain and potential alternatives, currently approved anti-obesity medications and best practices to individualize the selection process, and the use of testosterone in men with hypogonadism and obesity.

Topics: Androgens; Anti-Obesity Agents; Antidepressive Agents; Antihypertensive Agents; Antipsychotic Agents; Appetite Depressants; Benzazepines; Bupropion; Drug Combinations; Fructose; Humans; Hypoglycemic Agents; Hypogonadism; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Testosterone; Topiramate; Weight Gain

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

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

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

Obesity is a growing epidemic and a major contributor to the global burden of disease. Obesity strains the healthcare systems and has profound economic and psychosocial consequences. Historically, pharmacotherapy for obesity has witnessed the rise and fall of several promising drug candidates that had to be eventually withdrawn due to unacceptable safety concerns. Currently four drugs are approved for chronic weight management in obese adults: orlistat, lorcaserin, phentermine/topiramate extended release and naltrexone/bupropion extended release. While lorcaserin and phentermine/topiramate were approved by US Food and Drug Administration (FDA) in 2012, after a gap of 13 years following the licensing of orlistat, naltrexone/bupropion has been recently approved in 2014. This review provides a brief overview of these current therapeutic interventions available for management of obesity along with the evidence of their safety and efficacy. Additionally, several novel monotherapies as well as combination products are undergoing evaluation in various stages of clinical development. These therapies if proven successful will strengthen the existing armamentarium of antiobesity drugs and will be critical to combat the global public health crisis of obesity and its associated co-morbidities.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Drug Combinations; Drug Therapy, Combination; Fructose; Humans; Lactones; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate

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

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

Topics: Anti-Obesity Agents; Appetite; Appetite Depressants; Benzazepines; Benzoxazines; Bupropion; Clinical Trials as Topic; Drug Approval; Drug Combinations; Drug Discovery; Energy Metabolism; Enzyme Inhibitors; Fructose; Glucagon-Like Peptide 1; Humans; Hypothalamus; Lactones; Lipase; Liraglutide; Metabolic Syndrome; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate

Obesity is quickly becoming the leading preventable cause of death in the USA. Over 60 obesity-related comorbidities exist which increase the complexity and cost of medical care in obese patients. Even a moderate weight loss of 5 % can reduce morbidity associated with these conditions. Lifestyle modification through caloric restriction and enhanced exercise and physical activity remain the first line treatment for obesity. The development of pharmacologic agents for the treatment of obesity has been challenged by both lack of efficacy and serious adverse side effects leading to their removal from market. Two new agents were recently approved by the US Food and Drug Administration to complement lifestyle modification in obese (BMI ≥30 kg/m(2)) and overweight patients (BMI ≥27 kg/m(2) and one obesity-related comorbidity). Lorcaserin is a novel serotonin 5-HT2C selective agonist which has been shown in three phase III studies to significantly reduce weight and cardiovascular risk factors such as diabetes. Phentermine/topiramate extended release (ER) is a novel combination of two agents which have individually been shown to significantly reduce weight. The combination agent phentermine/topiramate ER has been shown to reduce weight in overweight and obese subjects in a number of studies. This article reviews the pharmacology, clinical efficacy, and safety of these new agents compared to past and other presently available medications for the treatment of obesity.

Topics: Anti-Obesity Agents; Benzazepines; Drug Approval; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Topiramate; Treatment Outcome

Worldwide obesity prevalence has nearly doubled since 1980. Due to numerous co-morbidities, obesity represents a serious health and socioeconomic problem worldwide. Pharmacotherapy should be an integral part of comprehensive obesity management. Drug therapy can assist in weight loss and its maintenance in those individuals who do not achieve appropriate weight loss through lifestyle interventions alone. After the withdrawal of sibutramine from the market in 2010, orlistat, a lipase inhibitor, was the only remaining prescription drug approved for the long-term treatment of obesity. In 2012, phentermine/topiramate extended-release (PHEN/TPM ER) combination and lorcaserin were approved by the US FDA as novel medications for long-term weight management. Three major phase III trials conducted with each drug confirmed their efficacy in terms of weight loss/maintenance and improvement of cardiometabolic risks. No head-to-head studies between the two new anti-obesity drugs have been carried out. However, in the existing studies PHEN/TPM ER had a superior weight loss profile to lorcaserin but the incidence of adverse effects was lower with lorcaserin. Both drugs were well-tolerated, and adverse events were modest in intensity, dose dependent, rather rare, and tended to decrease with the duration of treatment. Major safety concerns regarding PHEN/TPM ER include elevations in resting pulse rate, teratogenicity, mild metabolic acidosis, and psychiatric and cognitive adverse events. Valvulopathy, cognitive impairment, psychiatric disorders, and hypoglycemia represent major safety concerns for lorcaserin. Although existing trials have not demonstrated any significant issues with PHEN/TPM ER-induced heart rate elevation and lorcaserin-induced valvulopathy, all safety concerns should be seriously taken into account in patients treated with either of these novel anti-obesity medications.

Topics: Anti-Obesity Agents; Benzazepines; Benzoxazines; Bupropion; Chemistry, Pharmaceutical; Drug-Related Side Effects and Adverse Reactions; Fructose; Glucagon-Like Peptide 1; Humans; Liraglutide; Naltrexone; Obesity; Phentermine; Topiramate

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: Adult; Aged; Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Benzazepines; Fructose; Humans; Lactones; Middle Aged; Obesity; Orlistat; Phentermine; Topiramate

Obesity is a major correlate of cardiovascular disease. Weight loss improves cardiovascular risk factors and has the potential to improve outcomes. Two drugs, phentermine plus topiramate and lorcaserin, have recently been approved by the US Food and Drug Administration for the indication of obesity; a third, bupropion plus naltrexone, is under consideration for approval. In clinical trials, these drugs cause weight loss and improve glucose tolerance, lipid profile, and, with the exception of bupropion plus naltrexone, blood pressure. However, their effect on cardiovascular outcomes is unknown. In defining appropriate roles for these drugs in preventive cardiology, it is important to remember the checkered history of drugs for obesity. New weight-loss drugs share the serotonergic and sympathomimetic mechanisms that proved harmful in the cases of Fen-Phen and sibutramine, respectively, albeit with significant differences. Given these risks, randomized cardiovascular outcomes trials are needed to establish the safety, and potential benefit, of these drugs. This review will discuss the history of pharmacotherapy for obesity, existing efficacy and safety data for the novel weight-loss drugs, and issues in the design of postapproval clinical trials.

Topics: Anti-Obesity Agents; Benzazepines; Bupropion; Cardiovascular Diseases; Clinical Trials as Topic; Drug Combinations; Fructose; Heart; Humans; Naltrexone; Obesity; Phentermine; Topiramate

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

To review the pharmacology, efficacy, and safety of phentermine/topiramate (PHEN/TPM) in the management of obese patients.. MEDLINE (1966-July 2012) was searched using the terms weight loss, obesity, phentermine and topiramate, phentermine, topiramate, Qnexa, Qsymia, and VI-0521. Additionally, the new drug application and prescribing information for PHEN/TPM were retrieved.. All studies considering the pharmacology, efficacy, and safety of PHEN/TPM were reviewed with a focus on efficacy and safety data from Phase 3 trials.. In 3 Phase 3 trials (EQUIP, CONQUER, and SEQUEL), treatment with PHEN/TPM consistently demonstrated statistically significant weight loss compared with placebo. After 56 weeks of treatment, percent weight loss achieved with PHEN/TPM was 10.6%, 8.4%, and 5.1% with 15/92 mg, 7.5/46 mg, and 3.75/23 mg, respectively (p < 0.0001). The 52-week extension study (SEQUEL) showed maintained weight loss over 2 years with 9.3% and 10.5% weight loss from baseline for 7.5/46 mg and 15/92 mg PHEN/TPM (p < 0.0001). A significantly higher proportion of patients achieved greater than 5%, 10%, or 15% weight loss with PHEN/TPM compared with placebo. Significant reductions in waist circumference, fasting triglycerides, and fasting glucoses were also attributable to PHEN/TPM. The drug was generally well tolerated in clinical trials. Adverse reactions occurring in 5% or more of study subjects included paresthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.. PHEN/TPM is a new, once-daily, controlled-release, combination weight-loss product approved as an adjunct to diet and exercise for chronic weight management of obese or overweight patients with weight-related comorbidities. PHEN/TPM is modestly effective and a viable option for patients interested in losing weight, although long-term safety data are lacking.

Topics: Anti-Obesity Agents; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Topiramate

Obesity is a world-wide epidemic associated with significant morbidity and mortality which costs billions of dollars per year. The associated related conditions are many and include heart disease, stroke, type II diabetes mellitus, sleep apnea and certain types of cancer. Given that it is a multifactorial problem, the treatments must also address the numerous causes associated with the development of obesity. The neurohormonal regulation of feeding and energy is a complex system often necessitating modification through more than 1 pathway to achieve weight loss. Therefore, in addition to lifestyle changes, attenuation of caloric intake and increase in caloric expenditure, pharmacotherapies, including combination medications, may prove beneficial in its treatment. Adding to the current available pharmacotherapies for obesity, the Food and Drug Administration has recently approved 2 new combination medications known as lorcaserin (Belviq) and phentermine-topiramate (Qsymia). As with these and other medications used for weight loss, clinical cautions, side effects, precise review of patients' medical history and selecting the appropriate medication are imperative. Additionally, close follow-up is necessary in patients undergoing treatment for weight loss. As weight loss progresses, patients who are currently undergoing concomitant treatment for comorbid diabetes and hypertension need to be monitored for appropriate changes in medications used to treat those conditions. Weight loss is often accompanied by improvement in blood pressure and glucose levels and therefore resting blood pressure and fasting and/or postprandial plasma glucose levels should be monitored at follow-up. Although unique to each individual, the benefits of weight loss are substantial and can improve well-being and physical health.

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

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

Obesity is ranked as one of the top 10 global health problems and the major concern deriving from it is the exposure of the population to a vast array of chronic pathologies such as cardiovascular and musculoskeletal disorders, type 2 diabetes, cancer, such as colon, breast and endometrial cancer, together with psychological disorders derived from this condition. The discovery that the clinically used anticonvulsants topiramate (TPM) and zonisamide (ZNS) induced weight loss in obese, epileptic patients, afforded the validation of the mitochondrial carbonic anhydrases (CAs, EC 4.2.1.1) VA and VB as targets for the development of antiobesity drugs.. This review deals with the scientific and patent literature regarding obesity or obesity-related pathologies, being particularly focused on the use of carbonic anhydrase inhibitors (CAI) such as TPM and ZNS which inhibit the de novo lipogenesis.. There is an urgent need of new drugs for the treatment of obesity. The identification that the mitochondrial CAs are implicated in the de novo lipogenesis allowed to consider selective inhibitors of such enzymes as useful for the development of new antiobesity drugs. Actually TPM was approved 1 year ago for this therapy, whereas ZNS is also an effective such agent. These compounds are the lead molecules in this field and an intense research is on the way in order to develop new compounds based on the selective inhibition of mitochondrial CA isoforms.

Topics: Animals; Anti-Obesity Agents; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Drug Design; Fructose; Humans; Isoxazoles; Lipogenesis; Mitochondria; Molecular Targeted Therapy; Obesity; Patents as Topic; Topiramate; Zonisamide

Obesity is now a major public health concern worldwide with increasing prevalence and a growing list of comorbidities and complications. The morbidity, mortality and reduced productivity associated with obesity and its complications result in a major burden to health care costs. Obesity is a complex chronic medical syndrome often with multiple different etiologic factors in individual patients. The long term successful management of obesity remains particularly challenging and invariably requires a multifaceted approach including lifestyle and behavioral modification, increased physical activity, and adjunctive pharmacotherapy. Bariatric surgery remains a last resort though at present it has the best results for achieving sustained robust weight loss. Obesity pharmacotherapy has been very limited in its role for long term obesity management because of the past history of several failed agents as well as the fact that presently available agents are few, and generally utilized as monotherapy. The recent FDA approval of the fixed drug combination of phentermine and extended release topiramate (topiramate-ER) (trade name Qsymia™) marks the first FDA approved combination pharmacotherapeutic agent for obesity since the Phen-Fen combination of the 1990s. This review details the history and clinical trial basis for the use of both phentermine and topiramate in obesity therapeutics as well as the results of clinical trials of their combination for obesity treatment in humans. The initial clinical approval trials offer evidence that this fixed drug combination offers synergistic potential for effective, robust and sustained weight loss with mean weight loss of at least 10% of baseline achieved and sustained for up to 2 years in over 50% of subjects treated. It is anticipated that this agent will be the first in a new trend of multi-agent combination therapy for the chronic adjunctive management of obesity.

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Drug Therapy, Combination; Fructose; Humans; Obesity; Phentermine; Topiramate

The aim of this article is to focus on the fixed-dose combination of phentermine and topiramate, a new antiobesity drug recently approved by the US FDA. The mechanisms of weight loss for each drug in monotherapy is described, followed by the rationale for its use as a combination therapy and a comprehensive review of recently published clinical trials that assessed its efficacy  and safety.

Topics: Anti-Obesity Agents; Appetite Depressants; Dose-Response Relationship, Drug; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

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, which results from an imbalance between calorie intake and expenditure, now affects over 500 million individuals worldwide. Lifestyle and behavioural interventions aimed at reducing calorie intake and/or increasing energy expenditure have limited long-term effectiveness due to complex and persistent hormonal, metabolic and neurochemical adaptations that defend against weight loss and promote weight regain. Surgical treatments for obesity, although highly effective, are unavailable or unsuitable for the majority of individuals with excess adiposity. Accordingly, few effective treatment options are available to most individuals with obesity. In the past, the use of antiobesity drugs, seemingly the logical choice to fill this therapeutic gap, has been limited because of a lack of efficacy, poor long-term adherence rates and serious adverse effects. In 2012, the FDA approved two new medications-lorcaserin and phentermine-topiramate controlled release-and is currently reviewing the resubmission of naltrexone sustained release-bupropion sustained release. This Review presents the available data on the efficacy and safety of these three medications and discusses future perspectives and challenges related to pharmacological weight management.

Topics: Appetite Depressants; Benzazepines; Drug Combinations; Fructose; Humans; Life Style; Obesity; Phentermine; Topiramate

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

The incidence of obesity and its associated comorbidities have significantly increased over the years with adverse health and financial consequences for society. Lifestyle changes are essential for the prevention and treatment of obesity but their benefit appears limited as inadequate and nonsustained weight loss results have been reported. Pharmacotherapy is frequently advocated as part of a weight loss strategy. In this review, we will discuss the antiobesity drugs with Food and Drug Administration approval and their cardiovascular implications.. Orlistat (Xenical) remains the single monotherapy that has approval in Europe. Topiramate (Topamax) and phentermine have long been approved in the United States, whereas lorcaserin and the extended release combination of phentermine with topiramate have recently gained approval. The development of single peptides targeting gut hormones or other host signals related to obesity may represent promising therapeutic options.. Despite the recent failures of a number of antiobesity drugs, the pharmacotherapy of obesity is progressing rapidly. Treating the obese cardiovascular patient has proven challenging. Efficacy, safety and the sustainability of weight loss are key areas of focus in drug development strategies.

Topics: Anti-Obesity Agents; Benzazepines; Cardiovascular Diseases; Fructose; Humans; Lactones; Obesity; Orlistat; Phentermine; Topiramate

Despite being one of the most prevalent chronic diseases, obesity was not recognized as such until very recently. Although linked to ubiquitous diseases like diabetes, hypertension, coronary artery disease, obstructive sleep apnea, and many others, targeted treatments are few. Diet, exercise, and behavior modification are the pillars of weight loss. When they alone do not achieve the required weight reduction, medications may be used for patients with a BMI above 30 or above 27 if obesity-related comorbidities are present. The spectrum of pharmacologic agents aimed at obesity treatment will be reviewed.. Two medications, phentermine and orlistat, have been the only agents approved many years ago and now still standing. Others have come and gone, removed from the market by the Food and Drug Administration (FDA) because of harmful side-effects. However, in the last few years, new drugs have started to emerge. Since 2012, two new medications phentermine-topiramate extended-release combination and lorcaserin have been FDA approved, while at least one more, naltrexone SR/bupropion SR combination is expected to be re-evaluated by the FDA in 2014.. Treating obesity is crucial as it will ultimately result in the prevention of many related chronic diseases and will decrease morbidity and mortality. Weight loss medications are a valuable part of the clinician's toolbox in the treatment of obesity and should be used when appropriate. Having a variety of medications would be a great asset to accommodate various patients' needs and pre-existing medical conditions.

Topics: Anti-Obesity Agents; Delayed-Action Preparations; Drugs, Investigational; Fructose; Humans; Lactones; Obesity; Orlistat; Phentermine; Topiramate; Weight Reduction Programs

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

Obesity is a chronic disease, and it requires chronic therapy. Hypertension, dyslipidemia, diabetes and cardiovascular diseases are leading causes of mortality in the modern world. All of them are strongly linked to obesity. While treating obesity, those conditions are also managed. Obese patients should always be treated through lifestyle interventions, though the results of such interventions are modest. Pharmacotherapy is a second step in the treatment of obesity, approved only when weight loss targets were not reached through lifestyle intervention. During the history of antiobesity drugs, many of them were withdrawn because of their side effects. Various guidelines recommend prescribing drug therapy for obesity through consideration of the potential benefits and limitations. Orlistat deactivates intestinal lipase and inhibits intestinal fat lipolysis. It is actually the only drug on the European market approved for the treatment of obesity. Orlistat therapy reduces weight to a modest extent, but it reduces the incidence of diabetes beyond the result achieved with lifestyle changes. Recently, some effective antiobesity drugs like sibutramine and rimonabant have been removed from the market due to their side effects. The new combination of topimarate and fentermine is approved in the US but not in Europe. The cost effectiveness of long-term pharmacotherapy of obesity is still an unresolved question.

Topics: Anti-Obesity Agents; Appetite; Combined Modality Therapy; Comorbidity; Cost-Benefit Analysis; Cyclobutanes; Diabetes Mellitus, Type 2; Diet, Diabetic; Drug Combinations; Exercise Therapy; Fructose; Gastrointestinal Hormones; Humans; Incretins; Insulin; Insulin Secretion; Intestines; Lactones; Leptin; Life Style; Models, Biological; Neuropeptides; Obesity; Orlistat; Phentermine; Phytotherapy; Piperidines; Plant Preparations; Pyrazoles; Rimonabant; Topiramate

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

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

Phentermine hydrochloride is a noradrenergic sympathetic amine approved for decades by the U.S. Food and Drug Administration (FDA) at doses as high as 37.5 mg/day for the short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide marketed since 1996, and approved by the FDA for seizure disorders at doses up to 400 mg/day and for the prevention of migraine headaches at doses up to 100 mg/day. Clinical trial data suggest topiramate promotes weight loss. The prescribing information of neither agent describes adverse drug interactions with the other. The controlled-release formulation of phentermine and topiramate at low, medium and full doses (with full dose containing 15 mg of phentermine hydrochloride and 92 mg of topiramate) promotes weight reduction, with clinical trial data supporting improvement in adiposopathic consequences leading to metabolic diseases. Reported adverse events with this combination agent are as expected, based upon knowledge of the individual components.

Topics: Animals; Anti-Obesity Agents; Appetite Depressants; Chemistry, Pharmaceutical; Drug Approval; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Randomized Controlled Trials as Topic; Topiramate; United States; United States Food and Drug Administration

To review the literature describing the efficacy of metformin and topiramate for the treatment of second-generation antipsychotic-induced weight gain.. Articles were identified by searching the MEDLINE database (from 1949 through January 2010) using the key words metformin, topiramate, antipsychotic, weight, weight gain, and obesity.. All randomized, placebo-controlled trials of metformin and topiramate were selected for review.. Weight gain due to second-generation antipsychotic use is a concern due to the risk of long-term metabolic and cardiovascular effects with these agents. These effects include obesity, hyperglycemia, and insulin resistance, all of which may contribute to diabetes and cardiovascular disease. Second-generation antipsychotics vary in the degree to which they cause weight gain, and dietary and lifestyle changes may not be feasible or sufficient in counter-acting this weight gain. Although other pharmacologic agents may be beneficial to prevent and treat antipsychotic-induced weight gain, metformin and topiramate have been the most extensively studied in this setting. Metformin acts peripherally to cause weight loss, while topiramate acts centrally. Review of 11 randomized, controlled trials demonstrates beneficial effects of metformin and topiramate in prevention and treatment of weight gain. Metformin is generally well tolerated and has been studied in pediatric patients, while topiramate is associated with more drug interactions and may possibly interfere with control of schizophrenia.. Data for the use of metformin and topiramate in the treatment and prevention of second-generation antipsychotic-induced weight gain are limited. Both may be effective in helping patients lose weight via mechanisms that have yet to be clearly defined. The use of metformin results in greater weight loss than topiramate, and topiramate is associated with more risks and may compromise the treatment of schizophrenia. Treatment of antipsychotic-induced weight gain with metformin may be an option after lifestyle and dietary changes have failed.

Topics: Anti-Obesity Agents; Antipsychotic Agents; Fructose; Humans; Hypoglycemic Agents; Metformin; Obesity; Psychotic Disorders; Randomized Controlled Trials as Topic; Topiramate; Weight Gain

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

Nighttime eating is categorized as either night eating syndrome (NES) or sleep-related eating disorder (SRED). These conditions represent an interruption in the overnight fast that characterizes human sleep. A critical review of the literature on NES and SRED will suggest that they are situated at opposite poles of a disordered eating spectrum. NES could be considered an abnormality in the circadian rhythm of meal timing with a normal circadian timing of sleep onset. Conversely, the feeding behavior in SRED is characterized by recurrent episodes of eating after an arousal from nighttime sleep with or without amnesia. Both conditions are often relentless and chronic. Multiple definitions of night eating have limited our ability to determine the exact prevalence of NES. Studies have suggested that central nervous system (CNS) serotonin modulation may lead to an effective treatment of NES. SRED is frequently associated with other sleep disorders, in particular parasomnias. Early studies have shown that the anti-seizure medication topiramate may be an effective treatment for SRED.

Topics: Anticonvulsants; Circadian Rhythm; Cross-Sectional Studies; Energy Metabolism; Feeding and Eating Disorders; Fructose; Homeostasis; Humans; Hypothalamus; Mass Screening; Obesity; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Serotonin; Sertraline; Sleep Wake Disorders; Topiramate

Obesity is a widespread disease in both the developed and developing world. Few pharmacological approaches for its treatment exist at this time.. This review summarises the currently approved obesity therapies and describes a possible new approach for the treatment and prophylaxis of this disease, based on the inhibition of carbonic anhydrases (CAs, EC 4.2.1.1), enzymes involved in several steps of de novo lipogenesis, both in the mitochondria and the cytosol of cells.. Topiramate and zonisamide, two antiepileptic drugs showing strong CA inhibitory properties, have been reported as an example of this approach, as clinical data have shown that these compounds induce persistent weight loss in obese patients.. The use of topiramate and zonisamide as lead molecules for the design of CA inhibitors targeting isozymes involved in lipogenesis could represent the beginning of a very promising new approach for the treatment of obesity.

Topics: Anti-Obesity Agents; Carbonic Anhydrase Inhibitors; Cytosol; Fructose; Humans; Isoxazoles; Mitochondria; Obesity; Topiramate; Zonisamide

Topiramate, a marketed antiepileptic drug, has been used to treat seizures and allied neurological problems since 1999. Recently, a series of newer findings for the use of topiramate have cropped up, which include Type 2 diabetes and obesity. In a series of clinical studies, a subset of neurological patients with Type 2 diabetes mellitus (T2DM) serendipitously showed better glycaemic control when treated with topiramate. It has since been demonstrated that topiramate can act both as an insulin secretagogue and sensitiser in T2DM animal models. Pathogenesis of Type 2 diabetes involves both beta-cell dysfunction and insulin resistance. Therefore, an agent that has dual action (insulin secretagougue and sensitisation) is preferred for T2DM. Topiramate seems to act through multiple mechanisms to ameliorate diabetic symptoms, some of them unknown. Hence, it becomes imperative to discuss its probable modes of action. Topiramate raises new hope as an antidiabetic agent or a potential new chemotype with a better safety profile for the treatment of T2DM.

Topics: Animals; Diabetes Mellitus, Type 2; Fructose; Humans; Hypoglycemic Agents; Obesity; Topiramate

The relentless rise in the prevalence of obesity predicts an exponential increase in the incidence of obesity-related complications. Medical and surgical treatments are necessary to prevent and treat obese co-morbidities, thereby avoiding disability and premature death. Interventions for obesity should be evaluated not by weight loss alone but against the new incidence in obesity-related co-morbidities, their remission or improvement. In combination with lifestyle measures, currently available pharmacological therapies -- rimonabant, orlistat and sibutramine -- achieve 5-10% weight loss, although a return to baseline is the norm after cessation of medication. All these agents demonstrate approximately 0.5% reduction in HbA1c in diabetic subjects; orlistat also reduces the new incidence of type 2 diabetes. Modest improvement in lipid profiles and reduced calculated cardiovascular risk is observed, but data on improvement of other co-morbidities are sparse. In contrast, surgical procedures that restrict food ingestion and/or curtail the absorptive surface area of the gut consistently achieve substantial weight loss, typically 20-35%, effect resolution of co-morbid conditions and improve quality of life. Although mortality is low, complications and hospitalisation are not uncommon after bariatric surgery. Intriguingly, surgical patients experience a reduction in appetite and report changes in food preference. Accentuation of the normal gastrointestinal hormonal response to food intake and possible changes in vagal afferent signalling are proposed to induce satiety. Increased understanding of body weight homeostasis and appetite regulation has provided an impressive list of potential targets for drug development, with the promise that single or combination therapy may ultimately challenge the supremacy of bariatric surgery.

Topics: Adipose Tissue; Amyloid; Anticonvulsants; Antidepressive Agents; Anxiety; Appetite Regulation; Bariatric Surgery; Body Mass Index; Bupropion; Cholecystokinin; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Depression; Diabetes Mellitus, Type 2; Female; Fluoxetine; Fructose; Ghrelin; Humans; Intra-Abdominal Fat; Islet Amyloid Polypeptide; Isoxazoles; Lactones; Leptin; Metabolic Syndrome; Metformin; Obesity; Obesity, Morbid; Orlistat; Oxyntomodulin; Peptide YY; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Sertraline; Sleep Apnea, Obstructive; Surgical Procedures, Operative; Topiramate; Zonisamide

Prader-Willi Syndrome (PWS) is a multisystemic genetic disease characterized by hypotonia, mental retardation, characteristic facial appearance, hyperphagia, and compulsive eating due to hypothalamic dysfunction. PWS is caused by loss of function of genes located in chromosome 15q11-q13, an area subject to genomic imprinting. Obesity is a major cause of increased morbidity and mortality among patients with PWS. The objective of this study was to analyze the therapeutic options available for the treatment of the obesity in PWS including pharmacological and surgical strategies.

Topics: Adolescent; Anti-Obesity Agents; Bariatric Surgery; Child; Child, Preschool; Female; Fluoxetine; Fructose; Humans; Infant; Infant, Newborn; Male; Mazindol; Obesity; Prader-Willi Syndrome; Selective Serotonin Reuptake Inhibitors; Topiramate

Obesity is strongly associated with conditions such as hypertension, diabetes mellitus and osteoarthritis that have known adverse health outcomes. The rising prevalence of obesity threatens to overburden our health care system. As a result, the need for safe and effective treatment options is urgent. Unfortunately, pharmacologic treatment options have been disappointing either because of poor side effect profiles or limited long-term efficacy. Our goal is to review currently available pharmacologic treatments and the data supporting their use so that practicing physicians may better incorporate them into a comprehensive, long-term treatment strategy for their patients. We focus on orlistat and sibutramine as these are the two medicines approved by the FDA for long-term treatment of obesity. In addition, we review briefly agents approved for short-term use as well as agents such as zonisamide and topiramate which have shown some promise as weight loss agents in specific clinical circumstances. Finally, we highlight one medicine currently in phase III clinical trials, an endocannabinoid receptor antagonist. Given the overwhelming research focus on this disease, it is likely that the coming years will bring more treatment options, raising the chance that our patients will have meaningful and sustained weight loss.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Fructose; Humans; Isoxazoles; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Selective Serotonin Reuptake Inhibitors; Topiramate; Zonisamide

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

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

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

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

Long-term success in obesity therapy is difficult to obtain, therefore drug therapy appears to be helpful. Until today, end-point studies for obesity drugs beyond the improvement of individual surrogate parameters are still missing. For all available drugs, medical treatment can be recommended only for a limited period of time due to the data of the studies and under consideration of side effects. Although a weight reduction leads to an improvement of cardiovascular risk factors and hence a reduction of cardiovascular morbidity and mortality should be expected, no study could prove it so far. Despite the positive influence on individual surrogate parameters, the use of the present available therapies appears underwhelming. In this overview the approved substances and perspectives of new therapeutic concepts are represented.

Topics: Anti-Obesity Agents; Anticonvulsants; Cyclobutanes; Fructose; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Topiramate

Weight overload and obesity became these last years a major health problem. However gain weight is a frequent side effect of a large number of psychotropics. This article proposes to discuss this potential while reviewing various molecules. This reveals that the atypical antipsychotics are most likely to induce weight gain, in particular clozapine and olanzapine. The tricyclic antidepressants and mirtazapine come next, with the majority of the mood stabilizers. The old antipsychotics seem to involve less gain of weight. The SSRI make lose weight in the first weeks of treatment, but induce a moderate weight gain on the long term.

Topics: Adolescent; Adult; Amisulpride; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Child; Clozapine; Dibenzothiazepines; Double-Blind Method; Female; Fructose; Haloperidol; Humans; Imidazoles; Indoles; Male; Obesity; Olanzapine; Piperazines; Placebos; Psychotropic Drugs; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Socioeconomic Factors; Sulpiride; Thiazoles; Time Factors; Topiramate; Valproic Acid; Weight Gain

The current obesity pandemic imposes a major global disease burden. Levels of non-communicable diseases such as type 2 diabetes, cardiovascular disease and some cancers will continue to rise unless an effective approach to treat obesity is found. Sustained weight loss of between 5-10% in the obese, by various means, confers marked health benefits. The currently available pharmacotherapies, orlistat and sibutramine, can induce weight loss of between 5-10% over 2 years or more. In trials, orlistat and sibutramine induced weight loss tends to be only between 2-4 kg greater than that produced by placebo control. However, this additional placebo subtracted weight loss produces marked additional improvements in diabetes and cardiovascular risk factors. Moreover, in the 4 year long XENDOS trial, the modest placebo subtracted weight loss produced by orlistat (2.8 kg) reduced the incidence of diabetes by over a third in those with normal glucose tolerance, and by nearly half in those with impaired glucose tolerance. Despite this, prescription sales of sibutramine in the US have apparently remained static and those of orlistat have fallen, with the drug now entering the global over-the-counter medication market. Recent data on potential anti-obesity drugs currently under going phase III trials, such as Rimonabant and Topiramate, demonstrate these drugs produce greater and more prolonged weight loss. Wider use of pharmacotherapy and enhanced efficacy for the next generation of anti-obesity drugs certainly promise to reduce obesity related illness if not halt the rise in obesity per se.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Energy Metabolism; Feeding Behavior; Fructose; Humans; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Topiramate

Topics: Adult; Appetite Depressants; Bupropion; Cyclobutanes; Diethylpropion; Fluoxetine; Fructose; Gastric Bypass; Gastroplasty; Humans; Lactones; Lipase; Obesity; Orlistat; Phentermine; Topiramate

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

Obesity is associated with considerable morbidity and decreased life expectancy. Weight gain is a commonly encountered problem associated with antipsychotic treatment. We reviewed the literature regarding the mechanisms of weight gain in response to these agents and eight substances implicated as potential obesity prevention or treatment: orlistat, sibutramine, fluoxetine, topiramate, amantadine, nizatidine and cimetidine, and metformin. Weight gain in response to antipsychotic treatment may be mediated through serotonergic, dopaminergic, adrenergic, cholinergic, histaminergic and glutaminergic receptors. Sex hormone dysregulation and altered insulin sensitivity have also been implicated. Two compounds, orlistat and sibutramine, have been shown to help prevent weight gain following a hypocaloric diet, but orlistat requires compliance with a fat-reduced diet, and sibutramine is unsuitable for patients taking serotonergic agents. The weight reducing effect of fluoxetine, even in conjunction with a hypocaloric diet, is only transient. Topiramate, amantadine and metformin may have adverse side-effects potentially outweighing the weight reducing potential. The effectiveness of cimetidine and nizatedine remains unclear. The hazards of these agents in a psychiatric population are discussed. It is concluded that the current evidence does not support the general use of pharmacological interventions for overweight patients treated with antipsychotic medication, although individually selected patients may benefit.

Topics: Amantadine; Antipsychotic Agents; Cimetidine; Cyclobutanes; Fluoxetine; Fructose; Humans; Lactones; Metformin; Nizatidine; Obesity; Orlistat; Topiramate; Weight Gain

Obesity is a general medical condition associated with an increase in morbidity and mortality. Although it would be desirable to use efficacious prevention programs, the success rates reported to date have been rather disappointing. In this observational study, a new drug treatment regimen was evaluated in five obese patients with a mean age of 39.6 +/- 4.2 years and an initial body mass index between 34.5 and 38.3 kg/m for a period of 96 weeks. The patients showed restrained and unrestrained eating patterns according to a German version of the Three-Factor Eating Questionnaire and were treated in an add-on regimen with the combination of three drugs with different anorectic properties that were consecutively introduced in an interval of 16 weeks. First, orlistat (120 mg three times a day) was given as a monotherapy. Sibutramine (15 mg in the morning) and then topiramate (in a dose dependent on appetite suppression and side effects) were added for a total duration of 48 weeks. A 48-week maintenance and relapse prevention treatment period with topiramate monotherapy followed the discontinuation of orlistat and sibutramine. This outpatient treatment procedure was tolerated well, although side effects occurred in all patients depending on the phase of the treatment regimen. After 96 weeks, the mean body mass index was 25.7 +/- 1.2 kg/m. Moreover, a normalization of eating patterns according to the Three-Factor Eating Questionnaire could be noticed. Factor 3, hunger, was significantly reduced. This treatment plan may be highly effective and safe in a subpopulation of obese patients.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Chemotherapy, Adjuvant; Cyclobutanes; Feeding Behavior; Female; Fructose; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Topiramate

By 24 mo postoperatively the model adjusted changes in systolic blood pressure/diastolic blood pressure (SBP/DBP) (mm Hg) were -24.44 (-34.46,-14.43)/-28.60 (-40.74,-16.46) in the PT + SG group versus -11.81 (-17.58,-6.05)/-13.89 (-21.32,-6.46) in the control group (SBP P = 0.02; DBP P = 0.03). At baseline 8 (61.5%) participants in the PT + SG arm and 22 (55.0%) in the control group used antihypertensives. Excluding patients lost to follow-up (n = 3), by 24 mo postoperatively, none of the PT + SG participants were on antihypertensives compared to 14 (41.2%) in the control group (P = 0.01).. Patients with BMI≥50 kg/m

Topics: Antihypertensive Agents; Gastrectomy; Humans; Laparoscopy; Obesity; Obesity, Morbid; Phentermine; Retrospective Studies; Topiramate; Treatment Outcome

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

To assess the pharmacokinetic (PK) and pharmacodynamic characteristics of VI-0521, a fixed-dose combination of immediate-release phentermine (PHEN) and extended-release topiramate (TPM) in adolescents aged 12 to 17 years with obesity, and to report weight loss and adverse events using this drug combination.. This was a multicentre, randomized, double-blind, parallel-design, placebo-controlled study in adolescents with obesity. A total of 42 adolescents were randomly assigned in a 1:1:1 ratio to placebo, or to a mid-dose (PHEN/TPM 7.5 mg/46 mg), or a top-dose (PHEN/TPM 15 mg/92 mg) of VI-0521. A total of 26 adolescents were included in the PK analysis (14 from the mid-dose group and 12 from the top-dose group).. On day 56, arithmetic means of terminal elimination half-life, apparent clearance (CL/F) and apparent central volume of distribution (Vc/F) were consistent across dose levels for both PHEN and TPM. Arithmetic means of CL/F and Vc/F for PHEN and TPM administered as a combination in adolescents with obesity were within 10% to 30% of those previously assessed in adults with obesity enrolled in phase II and III studies. A higher proportion of adolescents in both the mid- and top-dose groups (13.3% and 50.0%, respectively) compared with placebo (0.0%) reached ≥5% weight loss at day 56. The least squares (LS) mean change in systolic blood pressure from baseline to day 56 was -5.2 mmHg for the placebo group, -2.5 mmHg for the mid-dose group, and - 5.5 mmHg for the top-dose group. The LS mean change in diastolic blood pressure from baseline to day 56 was -2.4 mmHg for the placebo group, +3.8 mmHg for the mid-dose group, and + 2.0 mmHg for the top-dose group. Participants in the top-dose group had increases in heart rate from baseline of 4.1 bpm, while participants in the mid-dose group experienced a mean decrease in heart rate of 4.5 bpm at day 56. Both PHEN/TPM dose combinations were safe and well tolerated.. Treatment of adolescents with obesity using a fixed-dose combination of PHEN/TPM for 8 weeks resulted in exposure to PHEN and TPM that was comparable to that observed in adults, statistically significant weight loss, and a tolerable safety profile. These data indicate that both mid- and top-dose levels are appropriate for longer-term safety and efficacy studies in adolescents.

Topics: Adolescent; Anti-Obesity Agents; Child; Double-Blind Method; Fructose; Humans; Obesity; Phentermine; Topiramate

Prader-Willi Syndrome (PWS) is a rare genetic syndrome leading to severe behavioural disorders and mild cognitive impairment. The objective of this double-blind randomised placebo-controlled trial was to study the efficacy and tolerance of topiramate on behavioural disorders in patients with PWS. Participants (aged 12-45 years) had genetically confirmed PWS and severe irritability/impulsivity, eating disorders and/or obesity, and skin picking. Thirty-two participants received a placebo (PBO), and 30 participants received topiramate (TOP) (50-200 mg/day) for 8 weeks. The primary outcome was the rate of responders using the Clinical Global Impression-Improvement (CGI-I) scale. The secondary outcome measures included the Aberrant Behaviour Checklist, the Dykens Hyperphagia Questionnaire (DHK), the Self-Injurious Behaviour Scale (SIBS) and the body mass index (BMI). We found no significant difference in the primary outcome (the CGI-I): 9 (30%) patients were very much or much improved in the TOP group compared to 7 (22.6%) patients in the PBO group. However, the DHK behaviour and severity scores improved significantly more over time in patients treated with topiramate versus those receiving a placebo, with a significant dose-effect relationship. DHK scores were also significantly associated with genetic subtypes and hospitalisation status. The effects of topiramate on eating behaviours remained significant after adjusting for genetic subtype and hospitalisation. Topiramate had therefore a significant effect on eating disorders, with a dose-effect relationship. Given the burden of eating disorders in PWS, we believe that topiramate may become the first psychotropic option within the global care of obesity in individuals with PWS.

Topics: Adolescent; Adult; Body Mass Index; Child; Double-Blind Method; Feeding Behavior; Female; France; Humans; Hyperphagia; Logistic Models; Male; Middle Aged; Neuroprotective Agents; Obesity; Prader-Willi Syndrome; Severity of Illness Index; Surveys and Questionnaires; Topiramate; 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

Weight loss after pharmacotherapy varies greatly. We aimed to examine associations of quantitative gastrointestinal and psychological traits with obesity, and to validate the ability of these traits to predict responses of obese individuals to pharmacotherapy.. In a prospective study, we measured gastric emptying of solids and liquids, fasting and postprandial gastric volume, satiation by nutrient drink test (volume to fullness and maximal tolerated volume), satiety after an ad libitum buffet meal, gastrointestinal hormones, and psychological traits in 328 normal-weight, overweight, or obese adults. We also analyzed data from 181 previously studied adults to assess associations betwecen a subset of traits with body mass index and waist circumference. Latent dimensions associated with overweight or obesity were appraised by principal component analyses. We performed a proof of concept, placebo-controlled trial of extended-release phentermine and topiramate in 24 patients to validate associations between quantitative traits and response to weight-loss therapy.. In the prospective study, obesity was associated with fasting gastric volume (P = .03), accelerated gastric emptying (P < .001 for solids and P = .011 for liquids), lower postprandial levels of peptide tyrosine tyrosine (P = .003), and higher postprandial levels of glucagon-like peptide 1 (P < .001). In a combined analysis of data from all studies, obesity was associated with higher volume to fullness (n = 509; P = .038) and satiety with abnormal waist circumference (n = 271; P = .016). Principal component analysis identified latent dimensions that accounted for approximately 81% of the variation among overweight and obese subjects, including satiety or satiation (21%), gastric motility (14%), psychological factors (13%), and gastric sensorimotor factors (11%). The combination of phentermine and topiramate caused significant weight loss, slowed gastric emptying, and decreased calorie intake; weight loss in response to phentermine and topiramate was significantly associated with calorie intake at the prior satiety test.. Quantitative traits are associated with high body mass index; they can distinguish obesity phenotypes and, in a proof of concept clinical trial, predicted response to pharmacotherapy for obesity. ClinicalTrials.gov Number: NCT01834404.

Topics: Adult; Aged; Anti-Obesity Agents; Anxiety; Body Image; Body Mass Index; Cholecystokinin; Cohort Studies; Delayed-Action Preparations; Depression; Dipeptides; Drug Combinations; Fasting; Female; Fructose; Gastric Emptying; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity; Organ Size; Overweight; Peptide YY; Phentermine; Postprandial Period; Principal Component Analysis; Prospective Studies; Satiation; Self Efficacy; Stomach; Topiramate; Treatment Outcome

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

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

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

A 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

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

Long-term treatment with topiramate reduces body weight and improves insulin sensitivity in obese humans. Our aim was to evaluate the effect of topiramate treatment for 4 weeks on insulin sensitivity and secretion, independent of weight loss.. Randomized, double-blind, crossover, placebo-controlled study.. Thirteen obese (BMI 36.6 ± 1.3 kg/m(2) (mean ± s.e.m.)), insulin-resistant (homeostasis model of assessment-insulin resistance 2.0 ± 0.2) women received topiramate (T, maximum dose of 75 mg) and placebo (P) for 4 weeks, separated by a 4-week washout period. Insulin sensitivity and β-cell function were assessed using a two-step hyperinsulinemic euglycemic clamp with stable isotopes and a hyperglycemic clamp.. Hepatic and peripheral insulin sensitivities were not affected by topiramate treatment (glucose disposal rate (step 1 (insulin infusion rate 10 MU/M(2) per min) T: 17.5 ± 0.8 vs P: 18.5 ± 1.0 μmol/kg(LBM) per min, t=1.016, P=0.33; step 2 (insulin infusion rate 40 mU/m(2) per min) T: 27.9 ± 3.2 vs P: 28.8 ± 1.9 μmol/kg(LBM) per min, t=0.418, P=0.68)). Subjects lost a small amount of weight during the topiramate period (T: -1.0 ± 0.2 vs P: -0.1 ± 0.2 kg, t=2842, P=0.15). There were no changes in body fat mass, blood pressure, and fasting glucose. β-Cell function was not affected by topiramate as evidenced by an unaltered area under the curve of early (0-10 min; T: 1929.6 ± 265.7 vs P: 2024.7 ± 333.6 pmol/l, t=-0.357, P=0.73) and late (80-120 min; T: 28,017.7 ± 5029.9 vs P: 31,567.7 ± 5376.2 pmol/l, t=-1.481, P=0.16) phase insulin levels during hyperglycemia. The use of topiramate was associated with significant side effects such as paresthesia, nausea, dizziness, and concentration problems.. Low-dose topiramate treatment for 4 weeks, relative to placebo, had no significant effect on insulin sensitivity in overweight/obese adult females without established diabetes.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Double-Blind Method; Female; Fructose; Humans; Insulin; Insulin Resistance; Insulin Secretion; Middle Aged; Obesity; Topiramate; Young Adult

To evaluate safety and efficacy of phentermine 15 mg plus extended-release topiramate 92 mg for treatment of moderate to severe obstructive sleep apnea (OSA) in obese adults.. This phase 2, randomized, double-blind, placebo-controlled study included 2-week screening and 28-week treatment periods. Overnight polysomnography was performed at baseline, Week 8, and Week 28.. Single-center study conducted from August 2008 to September 2009.. Forty-five subjects with moderate to severe OSA not receiving positive airway pressure (PAP) treatment with body mass index of 30-40 kg/m(2).. Subjects were randomized to receive placebo (n = 23) or phentermine 15 mg plus extended-release topiramate 92 mg (n = 22). Both groups received lifestyle-modification counseling.. Primary endpoint, change in apnea-hypopnea index (AHI), significantly favored phentermine 15 mg plus extended-release topiramate 92 mg (-31.5 events/h, 95% CI: -40.0, -22.9) over placebo (-16.6 events/h, 95% CI: -25.0, -8.2) at Week 28 (P =0.0084). At Week 28, there was a 10.2% (95% CI: -12.7, -7.6; 10.8 kg, 95% CI: -13.5, -8.0) mean decrease in weight in the phentermine 15 mg plus extended-release topiramate 92 mg group compared with 4.3% (95% CI: -6.6, -2.0; 4.7 kg, 95% CI: -7.2, -2.2) in the placebo group (P = 0.0006) and a positive, significant (P = 0.0003) correlation between percent change in weight and change in AHI. Significant improvements in overnight oxygen saturation and reduction in blood pressure compared with placebo were observed. Phentermine 15 mg plus extended-release topiramate 92 mg was well tolerated with low adverse event rates.. Phentermine 15 mg plus extended-release topiramate 92 mg induced significant weight reductions and concomitant improvements in OSA and related symptoms vs placebo. This suggests weight loss mediated by phentermine 15 mg plus extended-release topiramate 92 mg may be useful in treatment of moderate to severe OSA in obese subjects unable or unwilling to comply with PAP treatment.

Topics: Administration, Oral; Adult; Aged; Anti-Obesity Agents; Appetite Depressants; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Obesity; Phentermine; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Topiramate; Treatment Outcome

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

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

In a single-center, placebo-controlled study, topiramate reduced binge eating and weight in patients with binge eating disorder (BED) and obesity. The current investigation evaluated the safety and efficacy of topiramate in a multicenter, placebo-controlled trial.. Eligible patients between 18 and 65 years with >or= 3 binge eating days/week and a body mass index (BMI) between 30 and 50 kg/m2 were randomized.. A total of 407 patients enrolled; 13 failed to meet inclusion criteria, resulting in 195 topiramate and 199 placebo patients. Topiramate reduced binge eating days/week (-3.5 +/- 1.9 vs. -2.5 +/- 2.1), binge episodes/week (-5.0 +/- 4.3 vs. -3.4 +/- 3.8), weight (-4.5 +/- 5.1 kg vs. .2 +/- 3.2 kg), and BMI (-1.6 +/- 1.8 kg/m2 vs. .1 +/- 1.2 kg/m2) compared with placebo (p < .001). Topiramate induced binge eating remission in 58% of patients (placebo, 29%; p < .001). Discontinuation rates were 30% in each group; adverse events (AEs) were the most common reason for topiramate discontinuation (16%; placebo, 8%). Paresthesia, upper respiratory tract infection, somnolence, and nausea were the most common AEs with topiramate.. This multicenter study in patients with BED associated with obesity demonstrated that topiramate was well tolerated and efficacious in improving the features of BED and in reducing obesity.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Bulimia Nervosa; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Obesity; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome

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

This is a randomized, placebo-controlled study of the weight-loss efficacy and safety of a controlled-release (CR) formulation of topiramate in overweight and obese patients with type 2 diabetes treated with diet and exercise alone or in combination with metformin.. Patients with type 2 diabetes, BMI > or =27 kg/m2, A1C >6.5 and <11.0%, treated with diet and exercise alone or in combination with metformin monotherapy were enrolled. Patients were randomized to placebo or topiramate CR titrated up to 175 mg/day. Treatment consisted of a 7-week titration phase followed by a 9-week maintenance phase.. A total of 111 subjects were randomized and analyzed. By the end of week 16, patients in the placebo and topiramate groups lost 2.5 and 6.0 kg, which represented 2.3 and 5.8%, respectively, of their baseline body weight (P < 0.001 vs. placebo). A1C improved from a baseline of 7.4% in the placebo and 7.6% in the topiramate groups to 7.1 and 6.7%, respectively, representing a 0.4 and 0.9% reduction from baseline, respectively (P < 0.001 vs. placebo). Topiramate also significantly reduced blood pressure and urinary albumin excretion. Adverse events were predominantly neuropsychiatric or central and peripheral nervous system related.. Topiramate CR treatment produced significant weight loss and meaningful improvements in A1C and blood pressure in obese patients with type 2 diabetes treated with diet and exercise or in combination with metformin. However, the central nervous system and psychiatric adverse event profile of topiramate CR makes it unsuitable for the treatment of obesity and diabetes.

Topics: Adult; Aged; Anti-Obesity Agents; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diet, Reducing; Double-Blind Method; Exercise; Female; Fructose; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Obesity; Placebos; Safety; Topiramate

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

Patients with bipolar disorder (BD) have an increased risk of obesity as well as psychotropic-associated weight gain. The objective of this study was to compare sibutramine and topiramate as adjunctive treatments for psychotropic-associated weight gain in overweight or obese outpatients with BD.. In this 24-week, open-label, flexible-dose, comparison trial, 46 outpatients with bipolar disorders who had a body mass index (BMI) > or =30 kg/m(2), or > or =27 kg/m(2) with obesity-related comorbidities, and psychotropic-associated weight gain were randomly assigned to receive sibutramine (n = 18; 5-15 mg/day) or topiramate (n = 28; 25-600 mg/day). The primary outcome measure was weight loss. Secondary measures included changes in BMI, percent body weight loss, and mood symptoms.. Patients randomized either to sibutramine or topiramate lost comparable amounts of weight (4.1 +/- 5.7 and 2.8 +/- 3.5 kg, respectively) and displayed similar rates of weight loss (0.85 and 0.82 kg/week, respectively). However, only four (22%) patients receiving sibutramine and six (21%) patients receiving topiramate completed the 24-week trial. In addition, the attrition patterns for the two drugs were different, with patients discontinuing topiramate doing so early in treatment and patients discontinuing sibutramine doing so throughout treatment. Also, higher ratings of manic and depressive symptoms significantly increased risk for early topiramate discontinuation compared to that for sibutramine.. Adjunctive sibutramine and topiramate may have comparable weight loss effects in overweight or obese bipolar patients with psychotropic-associated weight gain, but are each associated with similarly high discontinuation rates. In addition, they may have different attrition profiles. Compared to sibutramine, discontinuation of topiramate may be more likely to occur early in treatment and may be more dependent upon manic and depressive symptoms.

Topics: Adult; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Appetite Depressants; Bipolar Disorder; Body Mass Index; Cyclobutanes; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fructose; Humans; Lithium Compounds; Male; Middle Aged; Obesity; Psychiatric Status Rating Scales; Psychotic Disorders; Topiramate; Weight Gain

Topics: Anti-Obesity Agents; Benzodiazepines; Drug Administration Schedule; Fructose; Humans; Male; Obesity; Olanzapine; Schizophrenia; Topiramate; Weight Gain

Topics: Adolescent; Anti-Obesity Agents; Child; Child, Preschool; Cognition; Cognition Disorders; Female; Fructose; Humans; Male; Obesity; Topiramate

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 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

Prader-Willi syndrome is a multisystem neurogenetic obesity disorder with behavioral manifestations, including hyperphagia, compulsive behavior, self-injury, and mild to moderate mental retardation. In an 8-week open-label study, we evaluated adjunctive therapy with the anticonvulsant topiramate in 8 adults with Prader-Willi syndrome. Appetite was measured by a 1-hour access to food four times throughout the study and quantified with a visual analogue scale. Topiramate did not significantly change calories consumed, Body Mass Index, or increase self-reported appetite. In addition, there were no significant changes in compulsions. Surprisingly, topiramate treatment resulted in a clinically significant improvement in the self-injury (i.e., skin-picking) that is characteristic of this syndrome. Potential benefits of topiramate for self-injury should be evaluated further in controlled trials.

Topics: Adolescent; Adult; Anti-Obesity Agents; Body Mass Index; Female; Fructose; Humans; Male; Obesity; Prader-Willi Syndrome; Self-Injurious Behavior; Topiramate

Treatment of obese subjects with topiramate has recently been associated with significant weight loss in a 6-month dose-ranging study.. To investigate the long-term efficacy and safety of topiramate in obese subjects.. Randomised, double-blind, placebo-controlled study investigating three doses of topiramate: 96, 192, and 256 mg/day. All subjects also participated in a nonpharmacological weight-loss programme.. The study included 1289 subjects 18-75 y with a body mass index >/=30 kg/m(2) and <50 kg/m(2) in the absence of comorbidities, or >/=27 kg/m(2) and <50 kg/m(2) in the presence of controlled hypertension and/or dyslipidaemia.. The original study design was for a 6-week, single-blind, placebo run-in phase followed by an 8-week titration phase and 2 y of maintenance at the assigned dose. Sponsor ended study early in order to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Therefore, none of the subjects completed the full 2 y of treatment. Efficacy results are based on subjects who were enrolled early enough to have had an opportunity to complete 1 y at their assigned dose (modified intent-to-treat population, MITT) before learning of the decision to terminate the study. Safety results are based on all subjects who took at least one dose of study medication.. The safety population consisted of 1282 subjects, and the MITT efficacy population was 854 subjects. At 60 weeks, subjects in the placebo group lost 1.7% of their baseline body weight, while subjects in the topiramate 96, 192, and 256 mg/day treatment groups lost 7.0, 9.1, and 9.7%, respectively (P<0.001, MITT, last observation carried forward). Weight loss >/=5% of baseline weight was achieved by 18% of subjects in the placebo arm vs 54, 61, and 67% of subjects receiving topiramate 96, 192, and 256 mg/day, respectively; weight loss >/=10% was achieved by 6 vs 29, 40, and 44%, respectively (P<0.001). Weight loss was accompanied by significant improvements in blood pressure (systolic/diastolic changes of +0.4/+1.0, -3.1/-1.3, -5.7/-3.4, and -4.6/-2.4 mmHg were observed for placebo, topiramate 96 mg/day, 192 mg/day, and 256 mg/day, respectively, P<0.001) and glucose and insulin. The most common adverse events more frequently observed in topiramate-treated subjects occurred mostly during the titration phase and were related to the central or peripheral nervous system and included paresthesia, difficulty with concentration/attention, depression, difficulty with memory, language problems, nervousness, and psychomotor slowing.. Topiramate treatment of obese subjects over the course of 1 y resulted in clinically significant weight loss. Improvements were also observed in blood pressure and glucose tolerance.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Depression; Diet, Reducing; Double-Blind Method; Drug Administration Schedule; Exercise Therapy; Female; Follow-Up Studies; Fructose; Glucose Tolerance Test; Humans; Male; Middle Aged; Obesity; Paresthesia; Suicide; Topiramate

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

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

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

Binge eating disorder is associated with obesity. Topiramate is an antiepileptic agent associated with weight loss. The objective of this study was to evaluate topiramate in the treatment of binge eating disorder associated with obesity.. For this 14-week, double-blind, flexible-dose (25-600 mg/day) topiramate trial, 61 outpatients (53 women, eight men) with binge eating disorder who were obese (body mass index >/=30 kg/m(2)) were randomly assigned to receive topiramate (N=30) or placebo (N=31). The primary efficacy measure was binge frequency. The primary analysis of efficacy was a repeated-measures random regression with treatment-by-time as the effect measure.. Compared with placebo, topiramate was associated with a significantly greater rate of reduction in binge frequency, binge day frequency, body mass index, weight, and scores on the Clinical Global Impression severity scale and the Yale-Brown Obsessive Compulsive Scale (modified for binge eating). Topiramate was also associated with significantly greater reductions in binge frequency (topiramate: 94%, placebo: 46%) and binge day frequency (topiramate: 93%, placebo: 46%) and with a significantly higher level of response than placebo. The mean weight loss for topiramate-treated subjects who completed the study was 5.9 kg. Median topiramate dose was 212 mg/day (range=50-600). Nine patients (three receiving placebo, six given topiramate) discontinued because of adverse events. The most common reasons for discontinuing topiramate were headache (N=3) and paresthesias (N=2).. Topiramate was efficacious and relatively well tolerated in the short-term treatment of binge eating disorder associated with obesity.

Topics: Ambulatory Care; Anticonvulsants; Bulimia; Comorbidity; Double-Blind Method; Drug Administration Schedule; Fructose; Humans; Obesity; Placebos; Topiramate; Treatment Outcome

To study the pharmacokinetics of a combination oral contraceptive (OC) containing norethindrone and ethinyl estradiol during OC monotherapy, concomitant OC and topiramate (TPM) therapy, and concomitant OC and carbamazepine (CBZ) therapy in order to comparatively evaluate the pharmacokinetic interaction, which may cause contraceptive failure.. This randomized, open-label, five-group study included two 28-day cycles. Five groups of female subjects received oral doses of ORTHO-NOVUM 1/35 alone (cycle 1) and then concomitant with TPM or CBZ (cycle 2). The treatment groups were group 1, TPM, 50 mg/day; group 2, TPM, 100 mg/day; group 3, TPM, 200 mg/day; group 4, TPM, 200 mg/day (obese women); and group 5, CBZ, 600 mg/day. Group 4 comprised obese women whose body mass index (BMI) was between 30 and 35 kg/m(2). The BMI of the remaining four groups was < or =27 kg/m2.. Coadministration of TPM at daily doses of 50, 100, and 200 mg (nonobese) and 200 mg (obese) nonsignificantly (p > 0.05) changed the mean area under the curve (AUC) of ethinyl estradiol by -12%, +5%, -11%, and -9%, respectively, compared with OC monotherapy. A similar nonsignificant difference was observed with the plasma levels and AUC values of norethindrone (p > 0.05). CBZ (600 mg/day) significantly (p < 0.05) decreased the AUC values of norethindrone and ethinyl estradiol by 58% and 42%, respectively, and increased their respective oral clearance by 69% and 127% (p < 0.05). Because CBZ induces CYP 3A-mediated and glucuronide conjugation metabolic pathways, the significant increase in the oral clearance of ethinyl estradiol and norethindrone was anticipated.. TPM, at daily doses of 50-200 mg, does not interact with an OC containing norethindrone and ethinyl estradiol. The lack of the TPM-OC interaction is notable when it is compared with the CBZ-OC interaction.

Topics: Administration, Oral; Adult; Anticonvulsants; Area Under Curve; Body Mass Index; Carbamazepine; Contraceptives, Oral, Combined; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Interactions; Enzyme Induction; Ethinyl Estradiol; Female; Fructose; Humans; Mestranol; Metabolic Clearance Rate; Norethindrone; Obesity; Topiramate

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

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

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

Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown.. To quantify cost-effectiveness of different antiobesity drugs available for pediatric use.. This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature.. Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis.. Incremental cost-effectiveness ratio.. Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY.. In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.

Topics: Adolescent; Anti-Obesity Agents; Child; Cost-Benefit Analysis; Female; Humans; Liraglutide; Male; Obesity; Obesity, Morbid; Orlistat; Phentermine; Topiramate

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

Obesity and eating disorders can present together, and pose diagnostic and therapeutic challenges to the clinician. Generally, lifestyle interventions alone for the treatment of obesity have modest long-term effectiveness. Phentermine-topiramate extended release is a relatively new medication approved for weight reduction. Sleep-related eating disorder is a rare condition that is often underdiagnosed. Both conditions are chronic and require long-term management. There is no definitive treatment for sleep-related eating disorder, and therapeutic options are based on case reports.. A 35-year-old Caucasian male with a body mass index of 41.7 kg/m. Clinicians intending to help patients reduce body weight should screen for nocturnal eating and other eating disorders. Sleep-related eating disorder can be associated with significant morbidity and excess weight. Patients report adverse effects on quality of life as a result. Phentermine-topiramate extended release may be a good therapeutic option for patients presenting with comorbid obesity and sleep-related eating disorder. More research is needed to explore the efficacy and safety in this patient population.

Topics: Adult; Anti-Obesity Agents; Feeding and Eating Disorders; Fructose; Humans; Male; Obesity; Phentermine; Quality of Life; Sleep; Topiramate

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

To evaluate the effects of combining topiramate, bupropion and naltrexone in obesity-induced rats on their weight and subcutaneous adipose tissue.. A total of 40 male Wistar rats were induced to obesity for 8 weeks and the animals were divided into 8 groups: Ctr - control, G0 - Sham, G1 - oral saline solution (1.0mL/day), G2 - topiramate (20.0mg/kg) and bupropion (5.0mg/kg), G3 - naltrexone (20.0mg/kg), G4 - topiramate (20.0mg/kg), G5 - bupropion (5.0mg/kg) and G6 - topiramate (20.0mg/kg), bupropion (5.0mg/kg) and naltrexone (20.0mg/kg). During the experiment, all animals were weighed weekly. After 30 days of treatment animals were euthanized and their skin fragments were processed and stained with hematoxylin and eosin for morphological, morphometric and biochemical analyzes.. The only group that presented a decrease in the volume of subcutaneous adipose tissue was G3, but this decrease was not significant when compared with the other groups. The G4, the G5 and the G6 presented increased adipose tissue volume. Data showed that until the eighth week all animals increased their weight by approximately 50%. After treatment animals of all groups, except G3, increased their weight from 4% to 9% approximately. The G3 was the only group that lost weight, but this decrease was not significant.. The medicines studied were not efficient in reducing weight in obese rats. However, it should be considered that 30-day treatment period is not enough to observe the stronger effects of these drugs.

Topics: Animals; Bupropion; Humans; Male; Naltrexone; Obesity; Rats; Rats, Wistar; Subcutaneous Fat; Topiramate

The US FDA required a Risk Evaluation and Mitigation Strategy (REMS) for phentermine/topiramate, an anti-obesity medication, to prevent congenital malformations. No REMS is required for single-ingredient topiramate, which may be used off-label for the same purpose.. The aim of this study was to evaluate the impact of phentermine/topiramate approval in 2012 on subsequent topiramate use among patients with obesity.. We used a national insurance claims database to conduct an interrupted time-series study (2009-2015). Enrollees aged 18-65 years in each examined calendar quarter had full insurance benefits during that quarter and the preceding 6 months. We required patients to have an obesity diagnosis and no other conditions warranting topiramate use. We calculated topiramate or comparator drug (atorvastatin, metformin) initiation rates and evaluated changes in trends before and after 2012 (transition period).. Among topiramate users, 80% were female, and demographic characteristics remained consistent during the study period. Between 2009 and 2011, the topiramate initiation rate (95% confidence interval) among patients with obesity was 0.85 (0.73-0.98) per 1000 patients, with no significant upward or downward trend. In the first quarter of 2013, this rate had increased more than 2.5-fold (change: + 1.36 [1.19-1.52]). Metformin and atorvastatin initiation rates did not change. Topiramate initiation rates were threefold higher than phentermine/topiramate rates during the post-approval period.. Phentermine/topiramate approval was associated with increased topiramate use among patients with obesity. Prescribers are encouraged to enhance patient education and monitoring in such clinical use since topiramate prescribing information, compared with REMS for phentermine/topiramate, has less emphasis on preventing prenatal exposure.

Topics: Anti-Obesity Agents; Atorvastatin; Drug Approval; Drug Repositioning; Female; Fructose; Humans; Male; Metformin; Obesity; Phentermine; Pregnancy; Topiramate

We aimed to investigate the possible effect of topiramate (TOP, 0.02 mg/kg/day) on the livers in a high-fat diet (HFD)-induced obesity rat model. The other objective was to evaluate the relationship between TOP administration and NPY level using anti-NPY1R antibody.. Twenty-four adult female Wistar albino rats were randomly assigned into four equal groups as follow: control (CONT), obese (OBS), TOP, and OBS+TOP. All liver samples were investigated using the stereological analysis, as well as immunohistochemical and histopathological examination.. The total number of hepatocytes was significantly decreased in the OBS+TOP group compared to the CONT group or the OBS group (p < 0.05). We found a significant increase in the mean volume of liver in the OBS group compared to the CONT group (p < 0.05). Also, the mean volume of liver was significantly decreased in the OBS+TOP group compared to the OBS group (p < 0.05).. Taken together, our findings suggest that decreased liver volume is possibly attributed to TOP administration via setting the NPY level in the obese rats. Further, the side effects of TOP in combination with health risk of obesity may have led to an increase in hepatotoxicity and the subsequent hepatocyte loss (Fig. 7, Ref. 56). Text in PDF www.elis.sk Keywords: immunohistochemistry, liver, neuropeptide Y, obesity, rat, topiramate.

Topics: Animals; Diet, High-Fat; Disease Models, Animal; Female; Hypoglycemic Agents; Liver; Obesity; Rats; Rats, Wistar; Receptors, Neuropeptide Y; Topiramate

As with other psychiatric disorders, development of drugs to treat binge-eating disorder (BED) has been hampered by high placebo response and dropout rates in randomized controlled trials (RCTs). Although not approved for use in BED, several RCTs have suggested that topiramate is efficacious for BED in obese individuals. Using data from a positive investigator-initiated RCT of topiramate in 61 obese individuals with BED, the objective of the present study is (i) to develop a quantitative disease-drug-trial framework to inform future BED clinical trial designs, and (ii) to determine the optimal topiramate dose to achieve therapeutic efficacy. Disease-drug-trial models were developed separately for the two efficacy measures, namely, longitudinal normalized weekly binge-eating episode frequency (BEF) and binge day frequency (BDF). Model building consisted of (i) developing a placebo effect model that describes response from the placebo group, (ii) adding a drug effect to the placebo model to describe dose-response relationships, and (iii) developing a parametric time to event model to characterize patient dropout patterns. The placebo effect on normalized BEF and BDF over time demonstrated a maximum decrease of ~ 57% by 5 weeks. Participants had a higher dropout probability if no weight loss occurred during the trial period. The identified dose-response relationship demonstrated a daily dose of 125 mg was needed to exhibit a marked reduction in weekly BEF. The developed comprehensive disease-drug-trial model will be utilized to simulate different clinical trial designs to increase the success for future BED drug development programs.

Topics: Adult; Binge-Eating Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Development; Humans; Longitudinal Studies; Models, Psychological; Models, Statistical; Obesity; Off-Label Use; Patient Dropouts; Placebo Effect; Placebos; Randomized Controlled Trials as Topic; Research Design; Severity of Illness Index; Topiramate; Treatment Outcome

The aim of the present study is to investigate the effects of topiramate on the fat mass/obesity-associated protein (FTO) and on the neuropeptide Y (NPY) level in the hypothalamus depending on the recently increased prevalence of obesity.. In this study, twenty-four female rats were divided into four equal groups: Non-obese control, obese control, non-obese topiramate, and obese topiramate. Obese groups were fed with a 40% high-fat diet. At the end of the 9th week, the drug treatment started and the subjects were treated with topiramate once a day for 6 weeks. All animals underwent cardiac perfusion under high-dose anesthesia on the 15th week. Tissues were analyzed using biochemical, histological, and stereological methods.. In terms of neuron number in the arcuate nucleus area, a significant difference was observed among all groups (P < 0.01). The neuron number of the non-obese topiramate group was found to be significantly higher than that of the non-obese control group (P < 0.01). In the examination of the ventromedial nucleus of the entire group, it was observed that the neuron number of the non-obese control group was significantly lower than those of the other groups (P < 0.01). A significant increase in the NPY levels of the obese groups compared to the groups treated with topiramate was observed. Furthermore, the amount of the FTO protein increased in obese rats, while FTO and NPY levels decreased in the groups treated with topiramate.. In conclusion, the mechanism of the effect of topiramate to create a state of obesity is thought to involve the decrease in the levels of NPY and FTO.

Topics: Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Animals; Anti-Obesity Agents; Female; Hypothalamus; Neurons; Neuropeptide Y; Obesity; Rats; Topiramate

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

Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood-retinal barrier (BRB) and blood-brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice.. BBB and BRB permeability were assessed using. High-fat feeding caused increased entry of. Blood-brain barrier and blood-retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in

Topics: Animals; Blood-Brain Barrier; Blood-Retinal Barrier; Capillary Permeability; Carbonic Anhydrase Inhibitors; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Hippocampus; Hypothalamus; Male; Mice; Obesity; Oxidative Stress; Tight Junction Proteins; Topiramate

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

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

Topics: Adolescent; Amitriptyline; Child; Humans; Migraine Disorders; Obesity; Pediatric Obesity; Risk Factors; Screen Time; Sedentary Behavior; Topiramate

Obesity is a serious, chronic, relapsing disease of energy regulation, with strong genetic and early-life environmental determinants. Pharmacotherapy can be a useful adjunct to lifestyle intervention in effecting and maintaining clinically meaningful weight loss.. The aim of this article is to discuss the role of pharmacotherapy in obesity management. The efficacy, side effects and contraindications of available weight-loss medications are reviewed.. Long-term pharmacotherapy options, which can be effective in providing moderate weight loss, are available to treat obesity. Pharma-cotherapy should be considered an adjunct to lifestyle intervention in those with a body mass index (BMI) >30 kg/m30 kg/m2, or in those with a BMI of 27-30 kg/m2 and obesity-related complications. Safety and efficacy should be monitored closely on commencement, and the medication should be discontinued if there are safety or tolerability issues, or if.

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Drug Therapy; Drug Therapy, Combination; Fructose; Humans; Incretins; Lactones; Liraglutide; Obesity; Orlistat; Phentermine; Topiramate

To highlight the prevalence and impact of obesity in the United States and provide nurse practitioners (NPs) with an overview of pharmacotherapy options for treatment of overweight and obese individuals.. A comprehensive review of the literature was conducted using multiple databases, including PubMed, MEDLINE, and Ovid. Keywords used to obtain relevant articles included obesity and drug, or orlistat, topiramate/phentermine, lorcaserin, bupropion/naltrexone, and liraglutide.. Obesity is a prevalent disease with more than two thirds of Americans being considered overweight and one third being obese. Obesity places patients at an increased risk for many comorbidities that impact patient health as well as public health. There are currently five approved medications for the chronic management of obesity, two of which were approved in 2014. These pharmacological therapies are options to aid weight loss in patients that are obese or those who are overweight with additional risk factors.. NPs can assist patients struggling with their weight. With new pharmacotherapy options, there is an opportunity to add to diet and exercise in order to achieve increased weight loss. A decrease in obesity would potentially alleviate the burden on the healthcare system, both socially and economically, and improve patient quality of life.

Topics: Benzazepines; Bupropion; Disease Management; Fructose; Humans; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate; United States

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

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

This clinical practice guideline for treatment of DSM-5 feeding and eating disorders was conducted as part of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) Clinical Practice Guidelines (CPG) Project 2013-2014.. The CPG was developed in accordance with best practice according to the National Health and Medical Research Council of Australia. Literature of evidence for treatments of anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), other specified and unspecified eating disorders and avoidant restrictive food intake disorder (ARFID) was sourced from the previous RANZCP CPG reviews (dated to 2009) and updated with a systematic review (dated 2008-2013). A multidisciplinary working group wrote the draft CPG, which then underwent expert, community and stakeholder consultation, during which process additional evidence was identified.. In AN the CPG recommends treatment as an outpatient or day patient in most instances (i.e. in the least restrictive environment), with hospital admission for those at risk of medical and/or psychological compromise. A multi-axial and collaborative approach is recommended, including consideration of nutritional, medical and psychological aspects, the use of family based therapies in younger people and specialist therapist-led manualised based psychological therapies in all age groups and that include longer-term follow-up. A harm minimisation approach is recommended in chronic AN. In BN and BED the CPG recommends an individual psychological therapy for which the best evidence is for therapist-led cognitive behavioural therapy (CBT). There is also a role for CBT adapted for internet delivery, or CBT in a non-specialist guided self-help form. Medications that may be helpful either as an adjunctive or alternative treatment option include an antidepressant, topiramate, or orlistat (the last for people with comorbid obesity). No specific treatment is recommended for ARFID as there are no trials to guide practice.. Specific evidence based psychological and pharmacological treatments are recommended for most eating disorders but more trials are needed for specific therapies in AN, and research is urgently needed for all aspects of ARFID assessment and management.. Associate Professor Susan Byrne, Dr Angelica Claudino, Dr Anthea Fursland, Associate Professor Jennifer Gaudiani, Dr Susan Hart, Ms Gabriella Heruc, Associate Professor Michael Kohn, Dr Rick Kausman, Dr Sarah Maguire, Ms Peta Marks, Professor Janet Treasure and Mr Andrew Wallis.

Topics: Anti-Obesity Agents; Antidepressive Agents; Australia; Chronic Disease; Cognitive Behavioral Therapy; Feeding and Eating Disorders; Fructose; Harm Reduction; Humans; Lactones; New Zealand; Obesity; Orlistat; Psychiatry; Societies, Medical; Topiramate

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

Topics: Anti-Obesity Agents; Appetite Depressants; Benzazepines; Bupropion; Clinical Trials as Topic; Drug Approval; Drug Combinations; Europe; Fructose; Humans; Naltrexone; Obesity; Phentermine; Product Surveillance, Postmarketing; Topiramate; United States; United States Food and Drug Administration

The cornerstones of treatment for obesity, and even more so for simple overweight, are dietary measures and physical exercise. There are no drugs with a favourable harm-benefit balance in this setting. A fixed-dose combination of topiramate, an antiepileptic drug, and phentermine, an appetite-suppressant amphetamine, has been refused marketing authorisation in the European Union, after being licensed in the United States. There are no randomised controlled trials of topiramate + phentermine in the prevention of complications of obesity. In the three available placebo-controlled trials, patients treated with topiramate 46 mg per day + phentermine 7.5 mg per day for between 1 and 2 years lost about 6-8 kg more than patients who received a placebo. About one-quarter of this weight loss was regained within a year after treatment discontinuation. The known adverse effects of the two drugs composing this combination are additive, and include psychiatric disorders, cardiac arrhythmias and metabolic acidosis. The risk of serious cardiovascular disorders was not adequately studied during clinical trials. Many women of child-bearing age would be exposed to this combination, which can provoke fetal abnormalities, including cleft palate, if taken during pregnancy. In practice, the topiramate + phentermine combination has an unfavourable harm-benefit balance and has no place in the treatment of obesity.

Topics: Anti-Obesity Agents; Appetite Depressants; Drug Approval; Drug Combinations; European Union; Female; Fructose; Humans; Obesity; Overweight; Phentermine; Pregnancy; Topiramate; United States

Topics: Anti-Obesity Agents; Appetite Depressants; Fructose; Humans; Obesity; Phentermine; Substance-Related Disorders; Topiramate

The aim of this analysis was to evaluate changes in cardiovascular risk factors in obese patients with dyslipidemia and/or hypertension receiving phentermine (PHEN) and topiramate extended-release (TPM ER). In the 56-week, randomized, double-blind, placebo-controlled, multicenter CONQUER trial, PHEN/TPM ER demonstrated significant weight loss compared with placebo in overweight or obese participants with ≥2 weight-related co-morbidities. Participants with body mass indexes of 27 to 45 kg/m(2) were randomized to placebo, PHEN 7.5 mg/TPM ER 46 mg, or PHEN 15 mg/TPM ER 92 mg; participants also received lifestyle modification counseling. Primary end points were percentage weight loss and the proportion of participants achieving ≥5% weight loss. Additional end points were changes in lipid variables in the dyslipidemia population and blood pressure in the hypertensive population, stratified by treatment and magnitude of weight loss. PHEN/TPM ER produced significantly greater dose-related mean percentage weight loss compared with placebo in the subgroups of participants with dyslipidemia and those with hypertension. Regardless of treatment group assignment, participants with dyslipidemia who lost ≥5% of their baseline weight experienced significantly greater reductions in triglycerides (-14.5% to -39.8%), and in non-high-density lipoprotein cholesterol (-9.4% to -14.8%) than those losing <5% of their weight (p <0.05). Similarly, participants with hypertension at baseline showed reduced systolic blood pressure by -7.5 to -11.8 mm Hg (p <0.001 vs those with <5% weight loss). In conclusion, the dose-related weight loss induced by PHEN/TPM ER treatment was accompanied by significant improvements in cardiovascular disease risk factors in participants who had dyslipidemia or hypertension at baseline, suggesting that facilitating weight loss by augmenting lifestyle changes with pharmacotherapies may decrease the risk for cardiovascular disease in obese and overweight patients with co-morbidities.

Topics: Anti-Obesity Agents; Biomarkers; Body Mass Index; Cardiovascular Diseases; Comorbidity; Delayed-Action Preparations; Female; Fructose; Humans; Male; Middle Aged; Obesity; Phentermine; Risk; Topiramate

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

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

Topics: Drug Approval; Drug Therapy, Combination; Fructose; Humans; Obesity; Phentermine; Topiramate; United States; United States Food and Drug Administration

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

Topics: Appetite Depressants; Data Interpretation, Statistical; Drug Approval; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Risk Assessment; Topiramate; United States; United States Food and Drug Administration

Topiramate (TPM) treatment has been shown to reduce adiposity in humans and rodents. The reduction in adiposity is related to decreased food intake and increased energy expenditure. However, the molecular mechanisms through which TPM induces weight loss are contradictory and remain to be clarified. Whether TPM treatment alters hypothalamic insulin, or leptin signaling and action, is not well established. Thus, we investigate herein whether short-term TPM treatment alters energy balance by affecting insulin and leptin signaling, action, or neuropeptide expression in the hypothalamus of mice fed with a high-fat diet. As expected, short-term treatment with TPM diminished adiposity in obese mice mainly due to reduced food intake. TPM increased anorexigenic signaling by enhancing the leptin-induced leptin receptor/Janus kinase 2/signal transducer and activator of transcription 3 pathway and the insulin-induced insulin receptor substrate/Akt/forkhead box O1 pathway in parallel to reduced phosphatase protein expression in the hypothalamus of obese mice. These effects were independent of body weight. TPM also raised anorexigenic neuropeptides such as POMC, TRH, and CRH mRNA levels in obese mice. In addition, TPM increased the activation of the hypothalamic MAPK/ERK pathway induced by leptin, accompanied by an increase in peroxisome proliferator-activated receptor-coactivator α and uncoupling protein 1 protein levels in brown adipose tissue. Furthermore, TPM increased AMP-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation in peripheral tissues, which may help improve energy metabolism in these tissues. Together, these results provide novel insights into the molecular mechanisms through which TPM treatment reduces adiposity.

Topics: Animals; Fructose; Hypothalamus; Insulin; Leptin; Male; Mice; Obesity; Topiramate

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

Vivus' proprietary oral capsule containing phentermine and extended-release (ER) topiramate has been approved in the US for the treatment of obesity. Phentermine is an appetite suppressant, while topiramate is an anti-epileptic medication. The once-daily formulation, known as Qsymia™, is designed to produce weight loss by decreasing appetite and increasing satiety. The product is also in clinical development for sleep apnoea syndrome and type 2 diabetes mellitus. This article summarizes the milestones in the development of phentermine/topiramate ER leading to this first approval for obesity.

Topics: Anti-Obesity Agents; Appetite Depressants; Clinical Trials as Topic; Delayed-Action Preparations; Fructose; Humans; Obesity; Phentermine; Randomized Controlled Trials as Topic; Topiramate

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; Benzazepines; Body Mass Index; Drug Approval; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Topiramate; United States; United States Food and Drug Administration

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

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

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

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

Meralgia paresthetica is a mononeuropathy affecting the lateral femoral cutaneous nerve that is extremely rare in children. Two adolescent females, aged 11 and 13 years, presented due to tingling and pain on the side of the thigh of 2 to 3 weeks duration. The general examination revealed mild obesity; the neurological examination of both patients is normal except for pain, hypo- or hyperesthesia on the side of the quadriceps. An electromyogram was performed in the first case that reveals decreased conduction velocity of the affected lateral femoral cutaneous nerve. The younger child was treated successfully with diet and topiramate; the second patient's symptoms disappeared after initiating conservative measures. Meralgia paresthetica is probably underdiagnosed in the pediatric population. First-line treatment should be conservative, but topiramate may be useful for the treatment of meralgia paresthetica, although broader studies are needed to evaluate its true effectiveness in this pathological condition.

Topics: Adolescent; Anti-Obesity Agents; Child; Female; Femoral Neuropathy; Follow-Up Studies; Fructose; Humans; Muscle, Skeletal; Neural Conduction; Obesity; Pain; Pain Management; Topiramate; Treatment Outcome

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

Topics: Anti-Obesity Agents; Appetite Depressants; Bulimia Nervosa; Comorbidity; Cyclobutanes; Female; Fructose; Humans; Male; Neurotransmitter Uptake Inhibitors; Obesity; Placebos; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

Topics: Adult; Anti-Obesity Agents; Feeding Behavior; Fructose; Humans; Male; Obesity; Substance Withdrawal Syndrome; Topiramate; Weight Gain

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

Among the multiple mechanisms of action of topiramate, AMPA/kainate antagonism may be particularly interesting for the treatment of disorders characterized by conditioned cognitive and behavioral cue reactivity.. We report the case of a patient consulting primarily for obesity and cue triggered snacking, who responded well on topiramate at doses up to 50 mg. Coincidentally he reported on an improvement of compulsive nonparaphilic sexual behaviors (consumption of prostitution), which was also strongly triggered by environmental cues. Both addictive behaviors (snacking and consumption of prostitution) reoccurred after discontinuation of topiramate and again responded reintroduction of the drug.. The present case report of topiramate's effect on comorbid obesity and nonparaphilic addiction could be interpreted as a further indication that topiramate acts on the common pathway underlying conditioned behaviors and seems to be a treatment of behavioral disorders associated with environmental cues.

Topics: Adult; Anti-Obesity Agents; Behavior, Addictive; Comorbidity; Compulsive Behavior; Conditioning, Psychological; Cues; Eating; Fructose; Humans; Male; Obesity; Receptors, AMPA; Receptors, Kainic Acid; Recurrence; Sex Work; Sexual Behavior; Topiramate; Treatment Outcome

Topics: Adult; Anti-Obesity Agents; Bipolar Disorder; Female; Fructose; Humans; Male; Middle Aged; Obesity; Topiramate; Weight Gain

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

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

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

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

Children and adolescents with autistic spectrum disorders are treated with neuroleptics to limit behavioral disturbances such as aggression, hyperactivity and self-injury. They may experience substantial weight gain when undergoing treatment with atypical antipsychotics actually employed. Topiramate (TPM) is an antiepileptic medication that is being progressively demonstrating a wider spectrum of action, mainly as an agent for weight control and as a mood stabilizer. It was administered to a group of children and adolescents with autistic spectrum disorders with the aim of reversing weight gain. This is an open study over an observation period of 18 months of 10 children and adolescents, eight males and two females, mean age 13 years, SD+/-3.6, range 8-19 years with a diagnosis of autistic disorder or pervasive developmental disorder not otherwise specified according to DSM-IV. Starting dosage of TPM was 0.5 mg/kg followed by titration of 0.5 mg/kg on a weekly basis, up to 1-3 mg/kg/day as the maintenance dosage. Eight subjects were undergoing long-term treatment with risperidone, one with pimozide and one was temporarily not on antipsychotics. Six patients took TPM on a regular basis and four dropped out. Variable degrees of weight reduction were observed in four patients, two subjects showed weight increase. Behavioral adverse effects were observed in three patients causing rapid withdrawal of the medication. TPM should be used with caution in autistic spectrum disorders because this population has a high risk of behavioral disruption.

Topics: Adolescent; Adult; Anti-Obesity Agents; Antipsychotic Agents; Autistic Disorder; Behavior; Child; Female; Fructose; Humans; Male; Obesity; Topiramate; Weight Gain

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

Topics: Anti-Obesity Agents; Anticonvulsants; Cognition Disorders; Epilepsy; Fructose; Humans; Neuroprotective Agents; Obesity; Practice Guidelines as Topic; Practice Patterns, Physicians'; Topiramate

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

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

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

Topiramate, a novel antiepileptic agent, has shown promise in the treatment of bipolar disorder. Patients attending a bipolar specialty clinic and treated with topiramate were identified by chart review, and data were harvested from systematic prospective assessments used routinely in the clinic. Fourteen patients who received topiramate for an average of 22.4 weeks were identified. All but one of these patients were considered to be highly refractory to standard treatment and 13 met the criteria for at least one comorbid psychiatric condition. Nine of these patients (64%) experienced an increased level of functioning and decrease in symptom severity during treatment with adjunctive topiramate. Eleven patients remained on treatment for longer than 2 weeks. Eight of these patients (73%) experienced a significant improvement in their comorbid conditions. Patients with a body mass index (BMI) of > or = 28 (n = 4) experienced a mean weight loss of 29.7 lb while on topiramate. Topiramate appears to be a promising agent for the treatment of bipolar disorder associated with comorbid psychiatric conditions and obesity.

Topics: Adolescent; Adult; Anti-Obesity Agents; Anticonvulsants; Bipolar Disorder; Body Mass Index; Drug Resistance; Female; Fructose; Humans; Male; Middle Aged; Obesity; Prospective Studies; Psychiatric Status Rating Scales; Topiramate

Topiramate, a fairly new anticonvulsant, is increasingly being used as a mood stabilizer in bipolar and schizoaffective disorders. One common side effect is a reduced appetite that often results in weight loss. This finding raises the interesting question of whether both mood and body weight can be stabilized in patients who have gained weight while being treated with neuroleptics for one of the disorders mentioned above.. We studied the body weight, subjective sense of well-being, and psychopathology in two adolescent patients who were being treated with topiramate (alone or in combination with a neuroleptic drug). Both patients had reduced appetite, while body weight either remained stable or was reduced.. The patients reported both improved control of food intake and mood stabilization.. We conclude that adolescents with affective disturbance who have gained weight on neuroleptic drugs may benefit from topiramate in terms of mood stabilization and body weight control.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Combined Modality Therapy; Diet, Reducing; Dose-Response Relationship, Drug; Follow-Up Studies; Fructose; Humans; Male; Obesity; Psychotic Disorders; Topiramate

Psychopharmacology research aims to expand the therapeutic ratio between efficacy, on the one hand, and adverse events and safety, on the other. The novel antipsychotics are now the antipsychotics of choice in the treatment of bipolar disorders. They have the advantages of potential antidepressant properties and low risks of extrapyramidal side effects and, especially, of tardive dyskinesia. However, novel antipsychotics may also have varying propensities to cause side effects, such as somnolence, hyperprolactinemia, weight gain (sometimes significant), and possibly diabetes mellitus. The increasing use of these novel agents requires careful assessment and monitoring of emergent side effects and diligent consideration of associated medical complications. Two new anticonvulsants, lamotrigine and topiramate, have recently shown promise in the treatment of bipolar disorders. Most of their adverse effects can be avoided by slow titration toward the recommended doses. In contrast to carbamazepine and valproic acid, topiramate may be associated with weight loss.

Topics: Anticonvulsants; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Female; Fructose; Humans; Lamotrigine; Male; Obesity; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles; Topiramate; Triazines

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

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

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

Topics: Adult; 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: Agoraphobia; Alcoholism; Cyclohexanols; Depressive Disorder; Female; Fructose; Hallucinations; Humans; Infarction, Posterior Cerebral Artery; Middle Aged; Neuroprotective Agents; Obesity; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Topiramate; Venlafaxine Hydrochloride

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

Topics: Abnormalities, Drug-Induced; Acetates; Adult; Amines; Anti-Anxiety Agents; Anticonvulsants; Bipolar Disorder; Carbamazepine; Cognition Disorders; Cyclohexanecarboxylic Acids; Dizziness; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fructose; Gabapentin; gamma-Aminobutyric Acid; Heart Defects, Congenital; Humans; Lamotrigine; Nausea; Obesity; Stevens-Johnson Syndrome; Topiramate; Triazines; Valproic Acid

This study examined the effects of topiramate (TPM), a novel neurotherapeutic agent reported to reduce body weight in humans, on the components of energy balance in female Zucker rats.. A 2 x 3 factorial experiment was performed in which two cohorts of Zucker rats differing in their phenotype (phenotype: lean, Fa/?; obese, fa/fa) were each divided into three groups defined by the dose of TPM administered (dose: TPM 0, vehicle; TPM 15, 15 mg/kg; TPM 60, 60 mg/kg).. The reduction in body weight gain induced by TPM in both lean and obese rats reflected a decrease in total body energy gain, which was more evident in obese than in lean rats. Whereas TPM administration did not influence the intake of digestible energy in lean rats, it induced a reduction in food intake in obese animals. In lean, but not in obese rats, apparent energy expenditure (as calculated by the difference between energy intake and energy gain) was higher in rats treated with TPM than in animals administered the vehicle. The low dose of TPM decreased fat gain (with emphasis on subcutaneous fat) without affecting protein gain, whereas the high dose of the drug induced a reduction in both fat and protein gains. The effects of TPM on muscle and fat depot weights were representative of the global effects of TPM on whole body fat and protein gains. The calculated energetic efficiency (energy gain/energy intake) was decreased in both lean and obese rats after TPM treatment. TPM dose independently reduced hyperinsulinemia of obese rats, but it did not alter insulinemia of lean animals.. The present results provide sound evidence for the ability of TPM to reduce fat and energy gains through reducing energetic efficiency in both lean and obese Zucker rats.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Cohort Studies; Dose-Response Relationship, Drug; Energy Intake; Energy Metabolism; Feeding Behavior; Female; Fructose; Muscle, Skeletal; Obesity; Rats; Rats, Zucker; Time Factors; Topiramate; Weight Gain

Topics: Adult; Anticonvulsants; Bipolar Disorder; Comorbidity; Depressive Disorder; Female; Fructose; Humans; Obesity; Topiramate; Weight Gain