topiramate and Cardiovascular-Diseases

Patients with schizophrenia have increased prevalence rates for many cardiometabolic risk factors; the prevalence and severity of these risks increase after the institution of antipsychotic medication. Nearly 2 dozen different pharmacologic interventions have been trialed to prevent or attenuate antipsychotic-related cardiometabolic changes. Metformin (usually 1,000-1,500 mg/d) has emerged as the best-studied intervention; in short- and intermediate-duration randomized controlled trials, it has been shown to bring about improvements in weight and other anthropometric indices, in fasting sugar and other glycemic control indices, and in total cholesterol and other lipid metabolism indices. Topiramate and aripiprazole are other possible interventions with support in literature; besides improving metabolic outcomes, these drugs may improve indices of psychopathology, as well. Encouraging though the findings are, there are many unanswered questions that require attention in future research.

Topics: Anti-Obesity Agents; Antipsychotic Agents; Aripiprazole; Cardiovascular Diseases; Fructose; Humans; Hypoglycemic Agents; Metabolic Syndrome; Metformin; Schizophrenia; Topiramate

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

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

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

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

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

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

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

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

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