topiramate and Weight-Gain

Metformin is the most investigated pharmacological treatment of antipsychotics-induced weight gain (AIWG). Based on a systematic literature review, the first guideline for the treatment of AIWG with metformin was recently published.. To present a step-by-step plan, based on recent literature and clinical experience to monitor, prevent, and treat AIWG.. Literature search to give specific advice on the choice of antipsychotic medication, stop, dose reduction or switch of antipsychotic, screening, non-pharmacological and pharmacological interventions to prevent and treat AIWG.. Especially in the first year of antipsychotic treatment timely detection of AIWG through regular monitoring is pivotal. The best way to treat AIWG is to prevent its emergence by choosing an antipsychotic with a favourable metabolic profile. Secondly, by titration of antipsychotic medication to the lowest dose possible. Achieving a healthy lifestyle shows a limited beneficial effect on AIWG. Drug-induced weight loss can be attained by the addition of metformin, topiramate, or aripiprazole. Topiramate and aripiprazole can improve positive and negative residual symptoms of schizophrenia. The evidence on liraglutide is scarce. All augmentation strategies may cause side effects. Besides, in case of nonresponse augmentation therapy should be stopped to prevent unnecessary polypharmacy.. In the revision of the Dutch multidisciplinary guideline for schizophrenia, the detection, prevention, and treatment of AIWG deserves more attention.

Topics: Antipsychotic Agents; Aripiprazole; Humans; Metformin; Topiramate; Weight Gain

Antipsychotic-induced weight gain is an extremely common problem in people with schizophrenia and is associated with increased morbidity and mortality. Adjunctive pharmacological interventions may be necessary to help manage antipsychotic-induced weight gain. This review splits and updates a previous Cochrane Review that focused on both pharmacological and behavioural approaches to this problem.. To determine the effectiveness of pharmacological interventions for preventing antipsychotic-induced weight gain in people with schizophrenia.. The Cochrane Schizophrenia Information Specialist searched Cochrane Schizophrenia's Register of Trials on 10 February 2021. There are no language, date, document type, or publication status limitations for inclusion of records in the register.. We included all randomised controlled trials (RCTs) that examined any adjunctive pharmacological intervention for preventing weight gain in people with schizophrenia or schizophrenia-like illnesses who use antipsychotic medications.. At least two review authors independently extracted data and assessed the quality of included studies. For continuous outcomes, we combined mean differences (MD) in endpoint and change data in the analysis. For dichotomous outcomes, we calculated risk ratios (RR). We assessed risk of bias for included studies and used GRADE to judge certainty of evidence and create summary of findings tables. The primary outcomes for this review were clinically important change in weight, clinically important change in body mass index (BMI), leaving the study early, compliance with treatment, and frequency of nausea. The included studies rarely reported these outcomes, so, post hoc, we added two new outcomes, average endpoint/change in weight and average endpoint/change in BMI.. Seventeen RCTs, with a total of 1388 participants, met the inclusion criteria for the review. Five studies investigated metformin, three topiramate, three H2 antagonists, three monoamine modulators, and one each investigated monoamine modulators plus betahistine, melatonin and samidorphan. The comparator in all studies was placebo or no treatment (i.e. standard care alone). We synthesised all studies in a quantitative meta-analysis. Most studies inadequately reported their methods of allocation concealment and blinding of participants and personnel. The resulting risk of bias and often small sample sizes limited the overall certainty of the evidence. Only one reboxetine study reported the primary outcome, number of participants with clinically important change in weight. Fewer people in the treatment condition experienced weight gains of more than 5% and more than 7% of their bodyweight than those in the placebo group (> 5% weight gain RR 0.27, 95% confidence interval (CI) 0.11 to 0.65; 1 study, 43 participants; > 7% weight gain RR 0.24, 95% CI 0.07 to 0.83; 1 study, 43 participants; very low-certainty evidence). No studies reported the primary outcomes, 'clinically important change in BMI', or 'compliance with treatment'. However, several studies reported 'average endpoint/change in body weight' or 'average endpoint/change in BMI'. Metformin may be effective in preventing weight gain (MD -4.03 kg, 95% CI -5.78 to -2.28; 4 studies, 131 participants; low-certainty evidence); and BMI increase (MD -1.63 kg/m2, 95% CI -2.96 to -0.29; 5 studies, 227 participants; low-certainty evidence). Other agents that may be slightly effective in preventing weight gain include H2 antagonists such as nizatidine, famotidine and ranitidine (MD -1.32 kg, 95% CI -2.09 to -0.56; 3 studies, 248 participants; low-certainty evidence) and monoamine modulators such as reboxetine and fluoxetine (weight: MD -1.89 kg, 95% CI -3.31 to -0.47; 3 studies, 103 participants; low-certainty evidence; BMI: MD -0.66 kg/m2, 95% CI -1.05 to -0.26; 3 studies, 103 participants; low-certainty evidence). Topiramate did not appear effective in preventing weight gain (MD -4.82 kg, 95% CI -9.99 to 0.35; 3 studies, 168 participants; very low-certainty evidence). For all agents, there was no difference between groups in terms of individuals leaving the study or reports of nausea. However, the results of these outcomes are uncertain given the very low-certainty evidence.. There is low-certainty evidence to suggest that metformin may be effective in preventing weight gain. Interpretation of this result and those for other agents, is limited by the small number of studies, small sample size, and short study duration. In future, we need studies that are adequately powered and with longer treatment durations to further evaluate the efficacy and safety of interventions for managing weight gain.

Topics: Antipsychotic Agents; Betahistine; Famotidine; Fluoxetine; Humans; Melatonin; Metformin; Nausea; Nizatidine; Ranitidine; Reboxetine; Schizophrenia; Topiramate; Weight Gain

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

Weight gain is one of the most challenging issues in patients with schizophrenia treated with antipsychotics. Several meta-analyses have been conducted to review the efficacy of topiramate in reducing weight, however, several issues regarding the methodology had arisen of which make the results remain ambiguous.. We conducted a meta-analysis of randomised controlled trials about the use of topiramate in patients with schizophrenia for weight reduction. Ten double-blinded randomised placebo-controlled trials and seven open-label randomised controlled trials included 905 patients.. Patients treated with topiramate experienced a greater reduction in body weight and BMI. Patients in countries of the lower overweight population showed more significant BMI reduction. Besides, studies from the Middle East and South Asia showed the greatest effect in body weight change, followed by East Asia, then Europe/America. Topiramate group was outperformed control group with significant psychopathology improvement. No difference between two groups regarding the overall side effects.. Topiramate was significantly superior to control group in mitigating weight gain and psychopathology in antipsychotic-treated patients with schizophrenia. The effects of topiramate augmentation need further investigations in larger definitive studies using methodological rigor and thorough assessments.

Topics: Antipsychotic Agents; Humans; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Schizophrenia; Topiramate; Weight Gain

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

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

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

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

Clinical antipsychotic trials of intervention effectiveness showed that atypical antipsychotics (AAPs) were associated with significant weight gain and glucose intolerance. A few trials have shown topiramate to reduce weight gain in patients receiving AAPs, although this benefit has not been present in all trials.. This study aimed to determine topiramate therapy's impact on weight gain in patients receiving AAPs.. A systematic literature search of MEDLINE (1948 to July 8, 2011) and Cochrane CENTRAL (4th Quarter 2011) was conducted.. Eight trials (n = 336 participants) met our inclusion criteria: randomized controlled trial, evaluated topiramate in patients taking AAPs, and reported weight change during the treatment course.. Two investigators (S.M. and C.I.C.) used a standardized data abstraction tool to independently collect data, with disagreement resolved through discussion. The difference between the mean weight in the topiramate and control groups was calculated as the weighted mean difference with accompanying 95% confidence interval. A random effect model was used for all analyses.. Upon meta-analysis, we found that patients receiving topiramate lost weight or had attenuated weight gain compared to control patients (weighted mean difference, -2.83 kg; 95% confidence interval, -4.62 to -1.03).. Our meta-analysis shows that using topiramate can prevent or reduce weight gain associated with AAPs.

Topics: Anti-Obesity Agents; Antipsychotic Agents; Fructose; Humans; Topiramate; Treatment Outcome; Weight Gain

Less than half of patients with schizophrenia obtain full response to antipsychotic drugs and, while clozapine represents the treatment of choice for refractory psychosis, a significant number of individuals remain only partially responsive. Despite a need for augmentation in this subpopulation, to date clear choices have not been forthcoming. Because clozapine, along with the majority of second-generation agents (SGAs), are linked to metabolic disturbances, augmentation strategies that do not further exacerbate these side effects are needed. Topiramate, unlike other anticonvulsants used for augmentation purposes, has been associated with weight loss. This article reviews the safety and efficacy of topiramate in treatment-refractory schizophrenia, including effects on metabolic disturbances, which burden this population. While current evidence specifically examining improvements in psychopathology demonstrates small to moderate benefits with topiramate augmentation, a growing body of evidence suggests that topiramate may have beneficial effects on antipsychotic-induced weight gain. We conclude that topiramate's metabolic profile, taken together with a current lack of evidence supporting a particular augmentation strategy, argues for further well-controlled studies examining its potential as an augmentation strategy in schizophrenia.

Topics: Anticonvulsants; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Fructose; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Metabolic Diseases; Neuropsychological Tests; Schizophrenia; Schizophrenic Psychology; Topiramate; Weight Gain

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

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

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

Juvenile myoclonic epilepsy is a common idiopathic generalized epileptic syndrome that includes generalized myoclonic seizures and commonly generalized tonic-clonic and generalized absence seizures. Before the emergence of the newer antiepileptic drugs (AEDs) in the 1990s, valproate was the usual first-line treatment in both men and women. However, the frequent adverse effect of weight gain and the risk of teratogenicity have resulted in a search for alternative first-line therapies in women. Four new AEDs- lamotrigine, topiramate, levetiracetam, and zonisamide-have been used as monotherapy or adjunctive therapy for juvenile myoclonic epilepsy in small patient series. Because they are not associated with weight gain and because they may have less risk of teratogenicity than valproate, they have been proposed as alternative first-line agents in women who have childbearing potential. However, the new AEDs may not be effective for all the seizure types of juvenile myoclonic epilepsy, and valproate appeared overall more effective in a large comparative trial in idiopathic generalized epilepsy. In addition, valproate is often effective at lower doses that have less teratogenicity, and an extended-release preparation may be less likely to produce weight gain. The current review presents evidence and arguments supporting the use of a new AED and those supporting the use of valproate as the first-line treatment in a girl with newly diagnosed juvenile myoclonic epilepsy. The review then concludes with a compromise approach.

Topics: Anticonvulsants; Congenital Abnormalities; Delayed-Action Preparations; Drug Design; Epilepsy, Generalized; Female; Fructose; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Male; Myoclonic Epilepsy, Juvenile; Piracetam; Pregnancy; Risk Assessment; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Weight Gain; Zonisamide

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

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

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

Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side effects as well as adjunctive treatments to inhibit these has been of major interest. The aim of this study was to investigate in healthy male volunteers (age: 36 ± 11 years; BW: 84 ± 12 kg; BMI=25.5 ± 2.5) whether adjunctive topiramate (TPM) administration opposes OLZ-induced weight gain over the course of 14 days treatment. In addition, we investigated behavioral, endocrine and metabolic characteristics as underlying and potentially predictive factors for weight regulation and/or metabolic derangements associated with OLZ and TPM treatment. While adjunctive TPM indeed reduced OLZ-induced weight gain (P<0.05, Mann-Whitney U), behavioral/metabolic/endocrine characteristics of OLZ treatment were not affected by TPM. Using multiple regression analysis, BW gain was the key factor explaining metabolic disturbances (e.g., plasma insulin- LDL interaction: P<0.01, R(2)=.320), and cumulative food intake during treatment was the best denominator of BW gain (P<0.01, R(2)=.534). Neither TPM treatment, nor its circulating levels, contributed to variation observed in ΔBW. In a second multiple regression analysis, we observed that a low baseline thyrotropin profile (TSHAUC) before the start of drug treatment was associated with an increase in ΔBW over the course of drug treatment (P<0.05, R(2)=.195). Adding TSHAUC as covariate revealed that adjunctive TPM treatment did attenuate OLZ induced BW gain (P<0.05, ANCOVA). Further exploration of the circulating thyroid hormones revealed that individuals with a low plasma TSH profile were also those that were most sensitive to adjunctive TPM treatment blocking OLZ-induced ΔBW gain. Others have shown that OLZ-induced BW gain is associated with improvement in brief psychiatric rating scores (BPRS); adjunctive TPM treatment may be a solution specifically for those subjects susceptible to OLZ-induced rapid weight gain who-on a therapeutic level-benefit most of OLZ treatment.

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Down-Regulation; Drug Antagonism; Fructose; Healthy Volunteers; Humans; Male; Middle Aged; Olanzapine; Overweight; Prognosis; Thyrotropin; Topiramate; Weight Gain; Young Adult

The aim of this study was to explore the probable prophylactic effects and evaluate different doses of topiramate on body weight in patients treated with olanzapine.. This was a 12 week, double-blind, placebo-controlled clinical trial (Iranian Clinical Trial Registration Code: 201402085280N15) to assess the preventative effects and estimate the optimal dosage of topiramate in drug-induced weight gain. Sixty eight patients aged 18 to 60 that were hospitalized and treated with olanzapine between 2009-2011due to the onset of an acute episode of schizophrenia or a manic episode of bipolar I disorder were selected in Mashhad, the second largest city in the northeast of Iran. Patients were randomly assigned to 4 groups, including 1- placebo; 2- 50 mg/day; 3- 100 mg/day; and 4- 200 mg/day topiramate. Two psychiatrists assigned participants to an intervention group and followed up the treatment process. Raters weighed patients at baseline and also at weeks 1, 2, 4, 6, 8, and 12, respectively. Waist and wrist circumferences were measured at baseline and weeks 4, 8, and 12. Body weight, BMI, wrist, and waist circumference changes were outcome measures of the study. Collected data were analyzed by ANOVA, post hoc Tukey test, Kruskal-Wallis, Mann-Whitney U, and Cohen's d with SPSS version 14. A p-value of less than 0.05 was considered significant.. All outcome measures were significantly less than the placebo group compared to the topiramate groups at the end of the fourth week and continued to twelfth week. Nevertheless, there was no statistically significant difference in the measures of any of the topiramate groups with each other at any interval.. All doses of 50, 100, and 200mg were shown effective in preventing olanzapine-related obesity in schizophrenic and/or bipolar patients.

Topics: Adolescent; Adult; Anticonvulsants; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Psychometrics; Schizophrenia; Topiramate; Treatment Outcome; Weight Gain; Young Adult

Olanzapine associated weight gain (WG) is a major concern in patients with schizophrenia. The purpose of this study was to assess the efficacy of topiramate to prevent olanzapine induced WG in these cases. We also studied various metabolic parameters.. In this 12-week, double-blind, parallel group study, seventy-two drug-naïve, first-episode schizophrenia patients were randomized to receive olanzapine+placebo (olanzapine group) or olanzapine+topiramate (100mg/day) (topiramate group). Weight, body mass index, fasting glucose, insulin, insulin resistance (IR), leptin, lipids and blood pressure were assessed at baseline and at 12 weeks. The patients were clinically evaluated using Positive and Negative Syndrome Scale (PANSS) and were monitored for adverse effects.. Topiramate resulted in a weight loss of 1.27+/-2.28 kg (p<0.01), decrease in leptin (p<0.001), glucose, cholesterol, triglyceride levels and systolic and diastolic blood pressure. In the olanzapine group, there was a significant WG, hyperglycemia, hyperinsulinemia, increased IR, hyperleptinemia, hypercholesterolemia and hypertriglyceridemia (p<0.001).There was a greater clinical improvement (PANSS scores) (p<0.001) in the topiramate group. The adverse effects were well tolerated.. Topiramate could prevent olanzapine induced weight gain and adverse metabolic effects. It also results in a greater clinical improvement when used with olanzapine in schizophrenia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol; Double-Blind Method; Female; Fructose; Humans; Insulin; Lipids; Male; Metabolic Diseases; Middle Aged; Neuroprotective Agents; Olanzapine; Prospective Studies; Schizophrenia; Topiramate; Weight Gain; Young Adult

Glutamate antagonists such as topiramate have been proposed based on the glutamate hypothesis of schizophrenia because its properties encourage its exploration and possible development as a medication for the treatment of schizophrenia. A randomised, double-blind, placebo-controlled clinical trial was performed on 18- to 45-year-old patients with schizophrenia. Baseline information including vital signs, height, weight, smoking status, demographic characteristics, (past) psychiatric history, medication history and medication-related adverse effects were collected. Patients were randomly assigned to a topiramate or placebo group. Efficacy of medication was measured by administering Positive and Negative Syndrome Scale (PANSS), and tolerability of treatment was recorded on day 0 (baseline), day 28 and day 56. PANSS values (95% confidence interval) at baseline, day 28 and day 56 in the topiramate group were 96.87 (85.37-108.37), 85.68 (74.67-96.70) and 76.87 (66.06-87.69), respectively; compared with 101.87 (90.37-113.37), 100.31 (89.29-111.32) and 100.56 (89.74-111.37) in the placebo group. General linear model for repeated measures analysis showed that topiramate has lowered PANSS values significantly compared with the placebo group. Similar significant decline patterns were found in all three subscales (negative, positive and psychopathology sign). Clinical response (more than 20% reduction in PANSS) was significantly higher in topiramate-treated subjects than controls (50% vs 12.5%). Topiramate can be an effective medication in controlling schizophrenic symptoms, considering its effect on negative symptoms and controlling antipsychotic-associated weight gain.

Topics: Adolescent; Adult; Anti-Obesity Agents; Anticonvulsants; Antipsychotic Agents; Clozapine; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Schizophrenia; Schizophrenic Psychology; Topiramate; Weight Gain

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 study was to test the efficacy and safety of olanzapine + topiramate versus olanzapine monotherapy in the treatment of bipolar disorder (BPD) and treatment-attendant weight gain in children and adolescents.. Subjects (N = 40) were outpatients of both sexes, 6-17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) diagnosis of BPD (manic, hypomanic, or mixed) and Young Mania Rating Scale (YMRS) total score of >15 treated over 8-week periods in two partially concurrent open-label trials with olanzapine (n = 17) or olanzapine + topiramate (n = 23).. Subjects in both groups experienced a statistically significant reduction in YMRS scores after 8-week, open-label treatment with olanzapine (baseline YMRS = 26.7 +/- 9.5; end-point YMRS = 18.2 +/- 12.5, p = 0.04) and olanzapine +topiramate (baseline YMRS = 31.3 +/- 7.9; end-point YMRS = 20.4 +/- 11.4, p = 0.04). There was no difference in response between the two groups based on YMRS or Clinical Global Impressions-Improvement (CGI-I) scores. Adverse events were few and mild and similar between the two groups, with the exception of weight gain. The weight gain in the olanzapine group was 5.3 +/- 2.1 kg and the weight gain in the olanzapine + topiramate group was statistically significantly lower, 2.6 +/- 3.6 kg.. Augmentation of olanzapine with topiramate resulted in a reduced weight gain over the course of an 8-week, open-label trial when compared with olanzapine treatment alone, but did not lead to greater reduction in symptoms of mania.

Topics: Adolescent; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Drug Therapy, Combination; Female; Fructose; Humans; Male; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Topiramate; Weight Gain

Effectiveness of antidepressants and antiepileptic drugs has already been demonstrated for migraine prophylaxis as monotherapy. In the present study, the efficacy and tolerability of amitriptyline and topiramate combination is examined in the prevention of migraine attacks, in comparison to the monotherapy of each drug.. A total of 73 patients with migraine headache with or without aura are included in this single-center, double-blind, randomized, and controlled trial. Patients were assigned to receive topiramate alone, amitriptyline alone or a combination of these drugs. Frequency, duration and severity of migraine attacks, accompanied symptoms, depressive state, consumption of medications, side effects and patient satisfaction were evaluated.. All treatments resulted in significant improvements in all efficacy measures (p<0.001 for all comparisons). However, patients receiving combination treatment had higher patient satisfaction compared with other groups both at 8 and 12 weeks (p=0.006 and p<0.001, respectively). Patients receiving amitriptyline and combination treatments had better depression scores compared with the topiramate group. Combination group had fewer side effects with a less amount of amitriptyline consumption.. Amitriptyline and topiramate combination may be beneficial for patients with migraine and comorbid depression, particularly in terms of side effects and associated displeasure due to monotherapy.

Topics: Adult; Amitriptyline; Anticonvulsants; Antidepressive Agents, Tricyclic; Constipation; Disorders of Excessive Somnolence; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Patient Satisfaction; Time Factors; Topiramate; Treatment Outcome; Weight Gain

Study aims were threefold: (i) to determine the feasibility, potential efficacy and safety of topiramate as an aid to smoking cessation; (ii) to examine potential predictors of abstinence including gender; and (iii) to explore topiramate's effects on tobacco withdrawal and post-cessation weight gain.. Randomized, double-blind, placebo-controlled, 11-week clinical trial with a 6-week dosage titration period and 5 weeks of maintenance treatment.. Single-site, out-patient, randomized clinical trial.. Thirty-eight adult male and 49 female chronic smokers who smoked an average of > 10 cigarettes per day and who were motivated to try to quit smoking.. Random assignment to receive either topiramate (n = 43) up to 200 mg daily in divided doses or placebo (n = 44) orally combined with brief counseling over an 11-week period.. Carbon monoxide (CO)-confirmed 4-week prolonged abstinence rate during weeks 8-11. Changes in tobacco withdrawal, body weight and safety parameters were also assessed.. Overall, no significant increase in the prolonged abstinence rate was detected, but logistic regression analysis indicated significant gender-specific differences. Men treated with topiramate were nearly 16 times more likely to quit smoking than women on topiramate [37.5% versus 3.7%; odds ratio (OR) = 15.6; P = 0.016] and were roughly four times more likely to quit smoking than placebo-treated men (37.5% versus 13.6%; OR = 3.8; P = 0.098). Topiramate-treated men reported significantly lower tobacco withdrawal scores than both women taking topiramate and men on placebo. On average, male cessators on placebo gained 3.30 kg, whereas topiramate led to a 0.72 kg weight loss (P = 0.03). Study discontinuation rates due to adverse events (AEs) were significantly higher in the topiramate group (topiramate 23% versus placebo 2%). The most commonly reported AEs in the topiramate arm were paraesthesia, fatigue, difficulty with concentration/attention and nervousness.. Topiramate produced gender-specific effects on smoking cessation. Male smokers had markedly greater quit rates than female smokers and men were roughly four times more likely to quit smoking when treated with topiramate as compared to placebo. Topiramate was fairly well tolerated, although higher discontinuation rates were seen. Topiramate's triple effects aiding smoking abstinence, attenuating nicotine withdrawal and preventing post-cessation weight gain might make it a promising agent for treating tobacco addiction, at least in men.

Topics: Adult; Dose-Response Relationship, Drug; Epidemiologic Methods; Female; Fructose; Humans; Male; Neuroprotective Agents; Sex Factors; Smoking Cessation; Substance Withdrawal Syndrome; Topiramate; Weight Gain

Many children and adolescents with bipolar disorder (BD) do not adhere to the pharmacological treatment due to weight gain. This investigation aims to describe response, side effects, and weight changes in a sample of youths with BPD while receiving topiramate for 11 weeks during the treatment maintenance phase.. Ten consecutive outpatients with BPD (11-17 years) using a single mood stabilizer and/or an antipsychotic presenting weight gain over 5% of their baseline weight were enrolled in this 11-week protocol. Their medication was switched to topiramate during the first 4 weeks. The Young Mania Rating Scale (Y-MRS) was the main outcome measure to assess response to the treatment in a weekly basis. Side effects and weight were also assessed weekly.. In repeated-measure analysis of variance (ANOVA), we found a significant reduction in both the YMRS scores (F = 10.21; p ,0.01) and in weight (F = 8.04; p ,0.01) during the trial.. These initial findings suggesting antimanic effects for topiramate during the treatment maintenance phase associated with weight reductions indicate the need of randomized clinical trials assessing this clinical relevant issue.

Topics: Adolescent; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Body Mass Index; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fructose; Humans; Male; Psychiatric Status Rating Scales; Topiramate; Treatment Outcome; Weight Gain

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

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

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

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

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

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

The long-term effectiveness of topiramate (TPM) was evaluated in children with West syndrome previously refractory to antiepileptic drug (AED) therapy.. Children with infantile spasms who completed a pilot study were eligible to enter a long-term extension phase in which the dosages of TPM and other AEDs could be adjusted to optimal response (maximum, 50 mg/kg/day TPM). The mean duration of long-term therapy was 18 months in the 11 children who were followed; the mean TPM dosage was 29 mg/kg/day.. Eight (73%) children were continuing TPM therapy at the time data were analyzed; four (50%) children were spasm free, seven (88%) had experienced a > or =50% reduction in spasms, and three (38%) were able to achieve TPM monotherapy.. TPM was well tolerated in that no patients discontinued because of adverse events. The response achieved with TPM during the pilot study was maintained in most children.

Topics: Age of Onset; Anticonvulsants; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Female; Fructose; Humans; Infant; Male; Pilot Projects; Spasms, Infantile; Topiramate; Treatment Outcome; Video Recording; Weight Gain

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

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

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

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

Topics: Aggression; Antipsychotic Agents; Bipolar Disorder; Child; Humans; Metformin; Topiramate; Weight Gain

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

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

Weight regain (WR) after Roux-en-Y gastric bypass surgery (RYGB) starts to occur 2 years after surgery, ultimately affecting at least 25% of patients. A limited number of studies have evaluated the impact of antiobesity medications (AOMs) on this phenomenon.. This study reviewed the electronic medical records of 1,196 patients who underwent RYGB between 2004 and 2015. WR was evaluated by comparing each patient's weight during subsequent postoperative office visits to nadir weight (lowest weight after RYGB, n = 760), taking into consideration the interval during which WR occurred. Patients who were prescribed AOMs and came to follow-up visits were classified as adherent users, whereas those who missed their follow-up visits were considered nonadherent. This study used a linear mixed model, Cox regression, and generalized equation estimator to determine the impact of AOMs on WR trajectory, hazard ratio for time to event, and odds ratio for repeated event occurrence, respectively.. Despite the lack of a unified protocol for using AOMs, the three statistical models converged to show that phentermine and topiramate, used individually or in combination, can significantly reduce WR after RYGB.. Phentermine and topiramate are effective in mitigating WR after RYGB. Further studies are needed to help ascertain optimal use of AOMs after bariatric surgery.

Topics: Adult; Anti-Obesity Agents; Female; Gastric Bypass; Humans; Male; Middle Aged; Phentermine; Postoperative Period; Retrospective Studies; Topiramate; Weight Gain

Topics: Bariatric Surgery; Gastric Bypass; Humans; Obesity, Morbid; Phentermine; Topiramate; Weight Gain

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

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

Although some drugs used in the treatment of epilepsy are known to affect body weight, the hormonal factors responsible have not been sufficiently described. The purpose of this study was to compare insulin, leptin, neuropeptide Y and ghrelin levels in children with epilepsy receiving monotherapy with topiramate (TPM) and valproic acid (VPA), the drugs whose effects on body weight have been most discussed, with those of a control group.. 48 patients (25 VPA, 23 TPM) aged between 6 and 15.5 years, presenting to the Karadeniz Technical University Medical Faculty Pediatric Neurology Clinic, diagnosed with idiopathic epilepsy or location-related idiopathic epilepsy, and receiving VPA or TPM monotherapy for at least 6 months were included in the study. Twenty-five healthy subjects with similar demographic characteristics were enrolled as the control group. Blood samples were collected from the patient and control groups after fasting for at least 10-12 h and again 1 and 2 h postprandially. Body mass index (BMI) values were calculated for all cases. VPA levels, glucose, insulin, leptin, neuropeptide Y and ghrelin were investigated in all three separate blood samples.. Age, height, weight and BMI were similar between the patient and control groups. Significant weight gain was observed throughout treatment in the VPA group compared to the TPM group. High fasting and postprandial insulin levels were observed in the VPA group. VPA group leptin and neuropeptide Y (NPY) levels were also higher than in the TPM and control groups. No significant difference was determined in ghrelin levels in the patient groups compared to the controls.. Low blood sugar not being observed, even though insulin levels are high, after fasting and in the postprandial period in epileptic children receiving VPA is indicative of insulin resistance. The elevation in leptin and neuropeptide Y levels observed in the VPA group also suggest this.

Topics: Adolescent; Anticonvulsants; Biomarkers; Blood Glucose; Body Mass Index; Child; Epilepsy; Fructose; Ghrelin; Humans; Insulin; Leptin; Neuropeptide Y; Topiramate; Treatment Outcome; Valproic Acid; Weight Gain

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

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

We report a 49-year-old female migraineur who experienced paradoxical hyperphagia and concurrent intrusive food thoughts leading to rapid weight gain and a substantial increase in waist circumference. A significant reduction in migraine frequency was also observed during topiramate treatment, a widely used migraine prophylactic agent which is generally associated with weight loss. Withdrawal of topiramate saw appetite return to baseline levels, however, migraine frequency was again increased. Topiramate was reinitiated in combination with phentermine, a drug indicated for weight management, without reoccurrence of adverse effects. Migraine control was maintained and progressive weight loss ensued. Combination treatment with phentermine may be a useful strategy should other patients experience this adverse reaction while gaining therapeutic anti-migraine benefit from topiramate.

Topics: Appetite Depressants; Drug Therapy, Combination; Female; Fructose; Humans; Hyperphagia; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Phentermine; Topiramate; Weight Gain

We report a patient with a history of rare generalised tonic-clonic seizures and recurrent absence status who was diagnosed with a rare variant of idiopathic generalised epilepsy and absence status epilepsy. No other pathology was identified and MRI was normal. During a follow-up of 17 years, we recorded a single unilateral continuous, strictly subclinical, paroxysmal activity which lasted for at least several hours. No control was observed under treatment with phenobarbital, lamotrigine and topiramate. Absence status was aggravated with carbamazepine and generalised tonic-clonic seizures were not controlled with ethosuximide. Total seizure control was only possible with sodium valproate, which caused weight gain, and the patient has remained seizure-free for the past 10 years under 1,000 mg/d valproate and 200 mg/d topiramate. The recorded unilateral, long-lasting, subclinical spike-and-wave discharge is quite unusual for idiopathic generalised epilepsy and, in our opinion, occupies a transitional position between generalised and focal activity.

Topics: Adult; Anticonvulsants; Brain; Carbamazepine; Diagnosis, Differential; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Follow-Up Studies; Fructose; Humans; Lamotrigine; Phenobarbital; Secondary Prevention; Status Epilepticus; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Weight Gain

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

Intake of antiepileptic drugs (AEDs) during pregnancy can provoke severe and subtle fetal malformations associated with deleterious sequelae, reflecting the need for experimental investigations on the comparative teratogenic potential of these agents. We recently reported that prenatal exposure to vigabatrin and valproate, two AEDs which act through GABAergic mechanisms, induces hippocampal and cortical dysplasias in rodents. We have now investigated the effects of phenobarbital (PB, 30 mg/kg day) i.p.), a drug also endowed with GABAergic effects, and the new generation AEDs lamotrigine (LTG, 5-20mg/kg/day i.p.), topiramate (TPM, 10mg/kg/day i.p.), and levetiracetam (LEV, 50mg/kg/day i.p.) on brain development. Prenatal exposure to LTG induced hippocampal and cortical malformations in a dose-dependent manner, at maternal plasma concentrations within the clinically occurring range. These abnormalities were not observed after exposure to PB, TP and LEV. These observations raise concerns about potential clinical correlates and call for detailed comparative investigations on the consequences of AED use during pregnancy.

Topics: Animals; Anticonvulsants; Brain; Cell Count; Cell Movement; Dose-Response Relationship, Drug; Female; Fructose; Hippocampus; Immunohistochemistry; Lamotrigine; Levetiracetam; Litter Size; Malformations of Cortical Development; Neurons; Phenobarbital; Piracetam; Pregnancy; Rats; Rats, Wistar; Teratogens; Topiramate; Triazines; Weight Gain

Weight gain is a common adverse effect of many psychotropic medications including antipsychotics, antidepressants, and mood stabilizers. There is a growing body of evidence that topiramate may be useful as an add-on therapy to induce weight loss in patients who have experienced psychotropic-induced weight gain.. To determine the efficacy and tolerability of topiramate for treatment of weight gain in a naturalistic mental health clinic setting.. A retrospective chart review was conducted at a community mental health clinic. Subjects were non-elderly adults who received topiramate therapy beginning in 2002-2005 for documented weight gain during treatment with psychotropic drugs. Primary outcome measures included response rate (based on weight loss of any magnitude) and mean changes in weight and body mass index (BMI).. Forty-one patients were included in the study. There was a 58.5% (n = 24) response rate. Mean reductions in weight and BMI were approximately 2.2 kg and 0.5 points, respectively. Responders lost an average of 7.2 kg, whereas nonresponders gained an average of 5.0 kg. Patients with a baseline weight of at least 91 kg and those receiving a greater number of psychotropic medications were more likely to experience success with topiramate therapy. Of the 24 patients who responded to therapy, 22 experienced onset of weight reduction by the next clinic visit (1-4 mo) following either initiation of therapy or titration to the eventual therapeutic dose, and the usual rate of weight loss was 0.45-1.4 kg per month. Therapy was typically initiated at 50 mg/day. The mean maximum dose was 93.9 mg/day and the median maximum dose was 100 mg/day. Seven (17.1%) patients had documented adverse effects to topiramate therapy.. Topiramate therapy resulted in overall modest (ie, <2%) decreases in weight and BMI, but many patients experienced more impressive weight loss. Therapy was generally well tolerated.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Community Mental Health Centers; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Psychotropic Drugs; Retrospective Studies; Topiramate; Treatment Outcome; Weight Gain

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

Topics: Adult; Anticonvulsants; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fructose; Humans; Lithium; Panic Disorder; Topiramate; Weight Gain

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

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

The effectiveness of topiramate was evaluated in the treatment of recurrent binge eating and weight gain in patients with binge eating disorder (BED) and obesity who had undergone initially successful bariatric surgery.. The records of 3 consecutive patients with BED and obesity who presented to our clinic with recurrent binge eating and weight gain after undergoing initially successful bariatric surgery were reviewed. They were treated with topiramate for an average of 10 months.. All three patients reported complete amelioration of their binge eating symptoms and displayed weight loss (31.7 kg in 17 months, 14.5 kg in 9 months, 2 kg in 4 months, respectively) in response to topiramate (mean dose 541 mg).. Although anecdotal, these observations suggest that topiramate may be an effective treatment for patients with BED and obesity who experience recurrent binge eating and weight gain after initially successful bariatric surgery.

Topics: Adult; Body Mass Index; Bulimia; Female; Follow-Up Studies; Fructose; Gastric Bypass; Humans; Middle Aged; Obesity, Morbid; Recurrence; Risk Assessment; Sampling Studies; Severity of Illness Index; Topiramate; Treatment Failure; Treatment Outcome; Weight Gain

Topiramate (TPM) is a novel neurotherapeutic agent. Clinical studies reported that TPM treatment reduced body weight and decreased fasting blood glucose levels in obese patients with or without type 2 diabetes. It is unclear whether the blood glucose-normalizing phenomenon observed during TPM treatment is a primary effect or the consequence of reduced food intake and weight loss. In the present studies, we chronically treated female Zucker diabetic fatty (ZDF) rats (fed with a diabetogenic diet) and db/db mice with TPM (30-300 mg/kg/day) to examine the effect of TPM on hyperglycaemia and its relationship with food intake and body weight gain. Our data showed that TPM treatment markedly reduced blood glucose levels in both ZDF rats and db/db mice without a significant reduction in body weight gain. Pair-fed db/db mice treated with the vehicle alone did not exhibit a significant decrease in blood glucose levels compared with mice fed ad libitum. TPM treatment increased glucose-stimulated insulin release by 2-3-fold during an oral glucose tolerance test in both ZDF rats and db/db mice. We also observed a 1.4-fold increase of pancreatic insulin content and heightened insulin immunostaining in pancreatic beta cells in db/db mice treated with TPM. Our data suggest that the antidiabetic effect of TPM is independent of the changes in body weight gain and food intake. Improved glucose-induced insulin release may, in part, underlie the mechanisms by which TPM ameliorates the hyperglycaemia.

Topics: Abdomen; Adipose Tissue; Animals; Blood Glucose; Eating; Female; Fructose; Glucose Tolerance Test; Hyperglycemia; Hypoglycemic Agents; Insulin; Islets of Langerhans; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Pancreas; Rats; Rats, Zucker; Topiramate; Triglycerides; Weight Gain

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

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

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Interactions; Drug Therapy, Combination; Fructose; Humans; Leukopenia; Male; Topiramate; United Kingdom; Weight Gain

Olanzapine is an effective drug for the long-term treatment of bipolar disorder but is associated with burdensome weight gain. Topiramate is a novel anticonvulsant that may induce weight loss in some patients. This is the first study to address the long-term efficacy and impact on weight of the combination of olanzapine and topiramate in bipolar patients. Twenty-six Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar spectrum patients received olanzapine plus topiramate cotherapy for treatment of their manic (n = 14), hypomanic (n = 6), depressive (n = 2), and mixed (n = 1) symptoms for 1 year. Three rapid cycling patients were also enrolled despite being euthymic. Efficacy was assessed with the Young Mania Rating Scale, the Hamilton Depression Rating Scale, and the Modified Clinical Global Impressions for Bipolar Disorder. Weight, body mass index, and side effects were collected at every visit. Thirteen (50%) patients completed the 1-year follow-up. By intent-to-treat, patients significantly improved from baseline in Young Mania Rating Scale scores (P < 0.0001), Hamilton Depression Rating Scale (P < 0.05), and Modified Clinical Global Impressions for Bipolar Disorder subscales (mania P < 0.0001, depression P < 0.05, overall P < 0.0001). Most patients gained weight during the first month of combined treatment (mean weight gain 0.7 +/- 0.6 kg), but at the 12-month endpoint, the mean weight change was -0.5 +/- 1.1 kg. The combination of olanzapine and topiramate was efficacious for the long-term treatment of bipolar patients and appeared to carry some benefits for controlling weight gain. Given the limitations of the open, uncontrolled design, further trials are warranted with this combination.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Olanzapine; Statistics, Nonparametric; Topiramate; Treatment Outcome; Weight Gain

Topics: Bipolar Disorder; Child, Preschool; Drug Therapy, Combination; Female; Fructose; Humans; Risperidone; Topiramate; Weight Gain

Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have been associated with significant weight gain, a problem that frequently leads to noncompliance and premature discontinuation of treatment. Topiramate is a novel anticonvulsant that has also been used as a mood stabilizer and augmentation agent in mood disorders. Topiramate has been observed to have an interesting side effect of weight loss in some individuals. In this study, topiramate was added to the treatment regimen of patients with a primary DSM-IV anxiety disorder who had experienced substantial SSRI-induced weight gain, in an attempt to induce weight loss.. Topiramate was added to SSRI treatment in 15 anxiety disorder patients, starting at a dose of 50 mg/day and titrating up to a target daily dose of 100 mg/day, with a maximum dose of 250 mg/day. Subjects' weight was measured at baseline and after 5 and 10 weeks of treatment.. Before topiramate treatment, SSRI-treated subjects in this sample had gained a mean of 13.0 +/- 8.4 kg (28.6 +/- 18.5 lb). After the addition of a mean dose of 135.0 +/- 44.1 mg/day of topiramate for approximately 10 weeks, subjects lost a mean of 4.2 +/- 6.0 kg (9.3 +/- 13.3 lb).. Topiramate may have a role in managing SSRI-induced weight gain in anxiety disorder patients.

Topics: Adult; Anxiety Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Topiramate; Treatment Outcome; Weight Gain

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Drug Therapy, Combination; Fructose; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia, Paranoid; Topiramate; Weight Gain

Topics: Adult; Bipolar Disorder; Borderline Personality Disorder; Comorbidity; Drug Overdose; Feeding and Eating Disorders; Female; Fructose; Humans; Substance-Related Disorders; Topiramate; Weight Gain

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

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