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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Options for pharmacological management of obesity in patients treated with atypical antipsychotics. 1213 98

Self-injurious behaviour (SIB), most notably skin picking, has been described by various terms in the literature ranging from neurotic/psychogenic excoriations to compulsive/pathological skin picking. Prader-Willi Syndrome (PWS) is a neurogenetic multisystem disorder characterized by infantile hypotonia, mental retardation, short stature, hypogonadism, dysmorphic features, and hyperphagia with a high risk of obesity. Psychiatric manifestations include SIBs in the form of skin picking, nail biting and rectal gouging. Topiramate is a novel anti-epileptic medication without significant liability of weight gain. There are no published reports of topiramate being utilized in PWS or SIB. We report attenuation of SIB with resultant lesion healing in three PWS adults treated with topiramate in an 8-wk open-label trial. Although our findings should be treated with caution, they suggest that double-blind or cross-over studies with topiramate are warranted to establish the possible role of topiramate in attenuating SIB in PWS and other disorders that involve SIB.
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PMID:Topiramate attenuates self-injurious behaviour in Prader-Willi Syndrome. 1213 38

Topiramate, a novel antiepileptic agent, has shown promise in the treatment of bipolar disorder. Patients attending a bipolar specialty clinic and treated with topiramate were identified by chart review, and data were harvested from systematic prospective assessments used routinely in the clinic. Fourteen patients who received topiramate for an average of 22.4 weeks were identified. All but one of these patients were considered to be highly refractory to standard treatment and 13 met the criteria for at least one comorbid psychiatric condition. Nine of these patients (64%) experienced an increased level of functioning and decrease in symptom severity during treatment with adjunctive topiramate. Eleven patients remained on treatment for longer than 2 weeks. Eight of these patients (73%) experienced a significant improvement in their comorbid conditions. Patients with a body mass index (BMI) of > or = 28 (n = 4) experienced a mean weight loss of 29.7 lb while on topiramate. Topiramate appears to be a promising agent for the treatment of bipolar disorder associated with comorbid psychiatric conditions and obesity.
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PMID:Clinical outcome of adjunctive topiramate treatment in a sample of refractory bipolar patients with comorbid conditions. 1245 23

Topiramate is an anti-convulsant often used off-label for the treatment of several conditions, including obesity and schizophrenia. This case report describes palmar erythema as a side effect in a patient using topiramate for paranoid schizophrenia.
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PMID:Palmar erythema due to topiramate. 1517 70

Prader-Willi syndrome is a multisystem neurogenetic obesity disorder with behavioral manifestations, including hyperphagia, compulsive behavior, self-injury, and mild to moderate mental retardation. In an 8-week open-label study, we evaluated adjunctive therapy with the anticonvulsant topiramate in 8 adults with Prader-Willi syndrome. Appetite was measured by a 1-hour access to food four times throughout the study and quantified with a visual analogue scale. Topiramate did not significantly change calories consumed, Body Mass Index, or increase self-reported appetite. In addition, there were no significant changes in compulsions. Surprisingly, topiramate treatment resulted in a clinically significant improvement in the self-injury (i.e., skin-picking) that is characteristic of this syndrome. Potential benefits of topiramate for self-injury should be evaluated further in controlled trials.
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PMID:Effects of topiramate in adults with Prader-Willi syndrome. 1517 17

The current obesity pandemic imposes a major global disease burden. Levels of non-communicable diseases such as type 2 diabetes, cardiovascular disease and some cancers will continue to rise unless an effective approach to treat obesity is found. Sustained weight loss of between 5-10% in the obese, by various means, confers marked health benefits. The currently available pharmacotherapies, orlistat and sibutramine, can induce weight loss of between 5-10% over 2 years or more. In trials, orlistat and sibutramine induced weight loss tends to be only between 2-4 kg greater than that produced by placebo control. However, this additional placebo subtracted weight loss produces marked additional improvements in diabetes and cardiovascular risk factors. Moreover, in the 4 year long XENDOS trial, the modest placebo subtracted weight loss produced by orlistat (2.8 kg) reduced the incidence of diabetes by over a third in those with normal glucose tolerance, and by nearly half in those with impaired glucose tolerance. Despite this, prescription sales of sibutramine in the US have apparently remained static and those of orlistat have fallen, with the drug now entering the global over-the-counter medication market. Recent data on potential anti-obesity drugs currently under going phase III trials, such as Rimonabant and Topiramate, demonstrate these drugs produce greater and more prolonged weight loss. Wider use of pharmacotherapy and enhanced efficacy for the next generation of anti-obesity drugs certainly promise to reduce obesity related illness if not halt the rise in obesity per se.
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PMID:Clinical pharmacotherapy for obesity: current drugs and those in advanced development. 1547 53

Obesity is a growing worldwide epidemic that is associated with serious medical complications. Although diet and exercise are often effective treatment in the short run, the weight lost is usually regained unless intensive intervention is maintained. Pharmacological adjunctive measures are clearly needed, and topiramate is currently being investigated as a possible new therapy for obesity. This paper reviews three clinical trials of topiramate for weight reduction in obese subjects: a 6-month dose-ranging study, a 2-year study of weight loss, and a 44-week study in subjects who had previously lost weight on a low-calorie diet. All three studies found topiramate to be significantly more efficacious than placebo. Notably, weight loss continued for 1 year and, perhaps, could have continued for a longer period. Topiramate was generally well tolerated, with adverse events being mild to moderate and mostly related to the central nervous system. Paresthesia was a frequent occurrence, but it did not lead to withdrawal of >5% of the subjects in any study.
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PMID:Topiramate: a new potential pharmacological treatment for obesity. 1568 13

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.
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PMID:Management of atypical antipsychotic-induced weight gain in schizophrenic patients with topiramate. 1619 68

Initially synthesized as an oral hypoglycemic agent, topiramate was approved for use as an anticonvulsant in 1996. Its broad spectrum efficacy in epilepsy, including as monotherapy and in children, is well established. Topiramate has also been used in the management of nonepileptic neurologic and psychiatric conditions, including migraine prophylaxis (with firmly established efficacy), obesity (with some evidence of long-term maintenance of weight loss), substance dependence, bipolar disorder and neuropathic pain, and it has been investigated as a possible neuroprotective agent. Paresthesias and cognitive side effects are the most common troublesome adverse effects. Recent trends towards lower doses may help achieve the best combination of efficacy and tolerability.
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PMID:Topiramate for the treatment of epilepsy and other nervous system disorders. 1646 8

Topiramate (Topamax), primarily prescribed against epilepsy, was reported to reduce body weight and to ameliorate glycemic control in obese patients with diabetes. In rodent models of obesity and diabetes, topiramate treatment counteracts hyperglycemia and increases insulin levels upon glucose tolerance test. These observations suggest that topiramate might exert direct action on insulin secreting cells, in particular regarding obesity associated beta-cell dysfunction. In this study, INS-1E beta-cells were exposed for 3 days to the fatty acid oleate (0.4mM) and concomitantly treated with therapeutic concentrations of topiramate before measurements of insulin secretion and metabolic parameters. In healthy cells, topiramate had no acute or chronic effects on insulin release. Exposure of INS-1E cells to oleate for 3 days increased insulin release at basal 2.5mM glucose and blunted the response to stimulatory glucose concentration (15mM). Such lipotoxic effects were associated with impaired mitochondrial function, as evidenced by partial loss of resting mitochondrial membrane potential and reduced hyperpolarization in response to glucose. Oil-red-O staining and triglyceride measurements revealed lipid accumulation in oleate treated cells. Topiramate treatment counteracted oleate-induced lipid load and partially protected against mitochondrial membrane dysfunction. In particular, topiramate restored glucose stimulated insulin secretion, essentially by maintaining low insulin release at basal glucose. Topiramate increased expression of the nutrient sensor PPARalpha and of the mitochondrial fatty acid carrier CPT-1, correlating with enhancement of beta-oxidation rate. The data demonstrate that a drug originally used as mood stabilizer exerts a direct action on beta-cells, protecting against lipid-induced dysfunction.
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PMID:The antiepileptic drug topiramate preserves metabolism-secretion coupling in insulin secreting cells chronically exposed to the fatty acid oleate. 1693 63


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