topiramate and Hypertension

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 We contacted authors of relevant papers about further published and unpublished work..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(rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively.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

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

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

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

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

Calcitonin gene-related peptide (CGRP) is involved in migraine pathophysiology and blood pressure regulation. Although clinical trials have established the cardio-cerebrovascular safety profile of anti-CGRP treatment, limited high-quality real-world evidence exists on its long-term effects on blood pressure (BP). To address this gap, we examined the safety of anti-CGRP treatment on BP in patients with migraine headache in the Veterans Health Administration (VHA).. We emulated a target trial of patients who initiated anti-CGRP treatment or topiramate for migraine prevention between May 17th, 2018 and February 28th, 2023. We calculated stabilized inverse probability weights to balance between groups and then used weighted linear mixed-effect models to estimate the systolic and diastolic BP changes over the study period. For patients without hypertension at baseline, we estimated the cumulative incidence of hypertension using Kaplan-Meier curve. We also used weight mixed-effect Poisson model to estimate the number of antihypertension medications for patients with hypertension at baseline.. This analysis included 69,589 patients and 554,437 blood pressure readings. of these, 18,880 patients received anti-CGRP treatment, and they were more likely to be women, have a chronic migraine diagnosis and higher healthcare utilization than those received topiramate. Among patients without hypertension at baseline, we found no significant differences in systolic BP changes over the four-year follow-up between anti-CGRP (slope [standard error, SE] = 0.48[0.06]) and topiramate treated patients (slope[SE] = 0.39[0.04]). The incidence of hypertension was similar for anti-CGRP and topiramate group (4.4 vs 4.3 per 100 person-years). Among patients with hypertension at baseline who initiated anti-CGRP treatment, we found a small but persistent effect on exacerbating hypertension during the first four years of treatment, as evidenced by a significant annual 3.7% increase in the number of antihypertensive medications prescribed (RR = 1.037, 95%CI 1.025-1.048).. Our findings suggest that anti-CGRP treatment is safe regarding blood pressure in patients without hypertension. However, for those with baseline hypertension, anti-CGRP treatment resulted in a small but persistent increase in the number of antihypertensives, indicating an exacerbation of hypertension. Future studies are needed to evaluate the cardio-cerebrovascular safety of anti-CGRP treatment beyond the first four years.

Topics: Blood Pressure; Calcitonin Gene-Related Peptide; Female; Humans; Hypertension; Male; Migraine Disorders; Topiramate

To study topiramate's new functions according to the medicinal property combinations, in order to apply the traditional Chinese medicinal theory in discovering new purposes of old drugs.. According to New Traditional Chinese Medicinal Families--Chemical Traditional Chinese Medicines, the authors found out topiramate's property. Then based on the therapeutic principle of diabetes, hypertension, epilepsy and lung cancer, as well as the relations of efficacies and medicinal property combinations, they summarized the corresponding medicinal property combination modes, compared topiramate's medicinal property combination mode with corresponding medicinal property combination modes of these diseases, and predict topiramate's new functions.. According to the comparison, the corresponding medicinal property combinations were consistent with topiramate's medicinal property combinations as evidenced by corresponding literatures, whereas other medicinal property combinations were not.. Based on medicinal property combination modes, the authors screened topiramate's new functions according to e of TCM clinical experience, discovered topiramate's therapeutic effects on diabetes, hypertension and lung cancer in addition to epilepsy, and explore new drug function according to medicinal property combination modes, which could help greatly shorten the new drug R&D period.

Topics: Diabetes Mellitus; Drug Therapy, Combination; Drugs, Chinese Herbal; Fructose; Humans; Hypertension; Lung Neoplasms; Phytotherapy; Topiramate

Topiramate is an anticonvulsant medication that is widely used for migraine prophylaxis. Hypohidrosis and hyperthermia are 2 rare adverse effects of topiramate treatment, which have mainly occurred in pediatric epilepsy patients. Herein, we describe the first case of reversible hypohidrosis in an adult patient treated with topiramate for chronic migraine.

Topics: Adult; Anticonvulsants; Fever; Fluid Therapy; Fructose; Headache Disorders; Hot Temperature; Humans; Hypertension; Hypohidrosis; Infusions, Intravenous; Male; Migraine Disorders; Obesity, Morbid; Patient Education as Topic; Sleep Apnea Syndromes; Sweat Glands; Sweating; Topiramate; Treatment Outcome

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

To report a case of possible clonidine-induced hypertension (by Naranjo score) in a patient with a C4 spinal lesion.. Clonidine is a medication long used to treat hypertension, and it is still used in the treatment of refractory hypertension. Although effective, clonidine use is hindered by adverse effects and its dual mechanism of action.. A 39-year-old white, quadriplegic man with poorly controlled pain displayed many characteristics consistent with autonomic dysfunction (e.g., C4 spinal lesion, orthostatic hypotension, hypertension). The patient was routinely receiving transdermal clonidine and also received transdermal nitroglycerin paste as needed for control of acute hypertensive episodes. On the recommendation of the home healthcare pharmacists, clonidine was discontinued. Since that time, the patient's blood pressure and the use of emergent antihypertensive treatment have decreased significantly (maximum systolic and diastolic BP by approximately 50 and 25 mm Hg, respectively).. Many of the characteristics of autonomic dysfunction, such as refractory hypertension, can seem selective for the use of clonidine and, because of its reliance on central alpha(2)-activity for its hypotensive effects, clonidine may induce hypertension in patients with autonomic dysfunction. Clonidine should be used with great caution when autonomic dysfunction is suspected.

Topics: Adrenergic alpha-Agonists; Adult; Blood Pressure; Chronic Disease; Clonidine; Fructose; Humans; Hypertension; Male; Neuroprotective Agents; Pain; Pain Measurement; Paraplegia; Spinal Cord Injuries; Topiramate