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      Tratamiento farmacológico de la obesidad en niños Translated title: Pharmacological treatment of child obesity

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          Abstract

          El tratamiento de la obesidad es un problema complejo, y los cambios en el estilo de vida no siempre tienen resultados satisfactorios, por lo que se han utilizado diversos fármacos para tratar de combatirla y algunos han mostrado ser efectivos. Entre estos medicamentos se encuentran aquellos que suprimen el apetito, los que incrementan el gasto energético, y los que modifican la absorción o el metabolismo de macronutrimentos. Sin embargo, algunos de ellos, a pesar de haber sido aprobados, han tenido que ser retirados del mercado debido a su asociación con efectos adversos graves. En la actualidad, de los utilizados para bajar de peso, solamente 2 de ellos se encuentran aprobados en población pediátrica: orlistat y sibutramina. El tratamiento farmacológico no ha mostrado efectividad por sí mismo, ya que se trata de una enfermedad multifactorial que requiere involucrar la modificación de los hábitos de alimentación, incrementar la actividad física o de terapia conductual. Aún quedan diversas interrogantes por resolver, como: seguridad de los medicamentos a largo plazo, forma de evitar la recuperación de peso secundaria a cualquiera que sea la intervención utilizada, eficacia de un fármaco sobre otro, tiempo óptimo de inicio, y la duración necesaria del tratamiento. Debido a lo anterior, se sugiere reservar el tratamiento farmacológico a pacientes con comorbilidades asociadas, que no hayan respondido a un programa estructurado de reducción de peso, que comprendan las limitaciones y efectos adversos de los medicamentos y la necesidad de continuar con los cambios en el estilo de vida.

          Translated abstract

          The treatment for obesity is a complex problem and changes in life style not always render satisfactory results. For this reason different drugs have been used to lose weight and some of them have shown to be effective. Among these drugs, are those that suppress appetite, increase energy expenditure and others that modify nutrient absorption or metabolism. Nevertheless, some of them in spite of been approved, have been withdrawn of the market due to their association with serious and adverse effects. Nowadays, from all drugs used to lose weight, only 2 are approved for pediatric age: orlistat and sibutramine. The pharmacological treatment has shown ineffectiveness by itself, because obesity is a multifaceted disease that requires the modification of eating habits, increase in physical activity and/or a behavior therapy. Many questions still remain to be solved: safety of long term-effect, forms to avoid subsequent weight regain after any intervention, effectiveness, optimal time of beginning and duration of treatment. In conclusion, all these issues suggest to keep the pharmacological treatment for patients with associated comorbidities and who have not responded to a structured weight loss program, and counseling to understand the limitations and drug adverse effects, as well as the need to continue with changes in life style.

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          Most cited references101

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          Meta-analysis: pharmacologic treatment of obesity.

          In response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used. To assess the efficacy and safety of weight loss medications approved by the U.S. Food and Drug Administration and other medications that have been used for weight loss. Electronic databases, experts in the field, and unpublished information. Up-to-date meta-analyses of sibutramine, phentermine, and diethylpropion were identified. The authors assessed in detail 50 studies of orlistat, 13 studies of fluoxetine, 5 studies of bupropion, 9 studies of topiramate, and 1 study each of sertraline and zonisamide. Meta-analysis was performed for all medications except sertraline, zonisamide, and fluoxetine, which are summarized narratively. The authors abstracted information about study design, intervention, co-interventions, population, outcomes, and methodologic quality, as well as weight loss and adverse events from controlled trials of medication. All pooled weight loss values are reported relative to placebo. A meta-analysis of sibutramine reported a mean difference in weight loss of 4.45 kg (95% CI, 3.62 to 5.29 kg) at 12 months. In the meta-analysis of orlistat, the estimate of the mean weight loss for orlistat-treated patients was 2.89 kg (CI, 2.27 to 3.51 kg) at 12 months. A recent meta-analysis of phentermine and diethylpropion reported pooled mean differences in weight loss at 6 months of 3.6 kg (CI, 0.6 to 6.0 kg) for phentermine-treated patients and 3.0 kg (CI, -1.6 to 11.5 kg) for diethylpropion-treated patients. Weight loss in fluoxetine studies ranged from 14.5 kg of weight lost to 0.4 kg of weight gained at 12 or more months. For bupropion, 2.77 kg (CI, 1.1 to 4.5 kg) of weight was lost at 6 to 12 months. Weight loss due to topiramate at 6 months was 6.5% (CI, 4.8% to 8.3%) of pretreatment weight. With one exception, long-term studies of health outcomes were lacking. Significant side effects that varied by drug were reported. Publication bias may exist despite a comprehensive search and despite the lack of statistical evidence for the existence of bias. Evidence of heterogeneity was observed for all meta-analyses. Sibutramine, orlistat, phentermine, probably diethylpropion, bupropion, probably fluoxetine, and topiramate promote modest weight loss when given along with recommendations for diet. Sibutramine and orlistat are the 2 most-studied drugs.
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            Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial.

            The prevalence of overweight and obesity in children and adolescents is increasing rapidly. In this population, behavioral therapy alone has had limited success in providing meaningful, sustained weight reduction, and pharmacological treatment has not been extensively studied. To determine the efficacy and safety of orlistat in weight management of adolescents. Multicenter, 54-week (August 2000-October 2002), randomized, double-blind study of 539 obese adolescents (aged 12-16 years; body mass index [BMI] >or=2 units above the 95th percentile) at 32 centers in the United States and Canada. A 120-mg dose of orlistat (n = 357) or placebo (n = 182) 3 times daily for 1 year, plus a mildly hypocaloric diet (30% fat calories), exercise, and behavioral therapy. Change in BMI; secondary measures included changes in waist and hip circumference, weight loss, lipid measurements, and glucose and insulin responses to oral glucose challenge. There was a decrease in BMI in both treatment groups up to week 12, thereafter stabilizing with orlistat but increasing beyond baseline with placebo. At the end of the study, BMI had decreased by 0.55 with orlistat but increased by 0.31 with placebo (P = .001). Compared with 15.7% of the placebo group, 26.5% of participants taking orlistat had a 5% or higher decrease in BMI (P = .005); 4.5% and 13.3%, respectively, had a 10% or higher decrease in BMI (P = .002). At study end, weight had increased 0.53 kg with orlistat and 3.14 kg with placebo (P<.001). Dual-energy x-ray absorptiometry showed that this difference was explained by changes in fat mass. Waist circumference decreased in the orlistat group but increased in the placebo group (-1.33 cm vs +0.12 cm; P<.05). Generally mild to moderate gastrointestinal tract adverse events occurred in 9% to 50% of the orlistat group and in 1% to 13% of the placebo group. In combination with diet, exercise, and behavioral modification, orlistat statistically significantly improved weight management in obese adolescents compared with placebo. The use of orlistat for 1 year in this adolescent population did not raise major safety issues although gastrointestinal adverse events were more common in the orlistat group.
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              Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy.

              Congenital leptin deficiency is a rare, but treatable, cause of severe early-onset obesity. To date, two United Kingdom families of Pakistani origin carrying a frameshift/premature stop mutation, c.398delG (Delta133G), and one Turkish family carrying a missense mutation, c.313C>T (Arg(105)Trp), have been described. Affected subjects are homozygotes and manifest severe obesity and hyperphagia accompanied by metabolic, neuroendocrine, and immune dysfunction. The effects of recombinant leptin therapy have been reported in three children with the Delta133G mutation, and in all cases this has led to a dramatic resolution of clinical and biochemical abnormalities. We now report a Canadian child, of Pakistani origin but unrelated to the previously reported subjects, presenting with severe hyperphagia and obesity, who was found to be homozygous for the Delta133G mutation. In this child, 4 yr of therapy with sc injections of recombinant leptin provided additional evidence for the sustained beneficial effects of leptin replacement on fat mass, hyperinsulinemia, and hyperlipidemia. In addition, leptin administration corrected abnormal thyroid biochemistry and allowed the withdrawal of T(4) treatment, providing additional support for the role of leptin in the regulation of the human hypothalamic-pituitary-thyroid axis.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                bmim
                Boletín médico del Hospital Infantil de México
                Bol. Med. Hosp. Infant. Mex.
                Instituto Nacional de Salud, Hospital Infantil de México Federico Gómez (México )
                1665-1146
                December 2008
                : 65
                : 6
                : 547-567
                Affiliations
                [1 ] Hospital Infantil de México Federico Gómez Mexico
                Article
                S1665-11462008000600012
                9892054f-a284-4dbd-b7c9-6d3a741de2e9

                http://creativecommons.org/licenses/by/4.0/

                History
                Categories
                Pediatrics

                Pediatrics
                Obesidad,tratamiento,fármacos,niños,Obesity,treatment,drugs,child
                Pediatrics
                Obesidad, tratamiento, fármacos, niños, Obesity, treatment, drugs, child

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