RESUMO
1. To test the hypothesis that lithium-induced body weight gain is related to an unbalance in the reproductive hormones, lithium carbonate (900 mg/day) or placebo was administered to healthy men for 1 month. 2. Body weight, skin folds and the serum levels of thyrotropic hormone, tetraiodothyroxine, prolactin, follicle-stimulating hormone, luteinizing hormone, testosterone (T5), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2), cortisol, the ratios E2/T5 and T5/DHEA-S, and blood lipids were evaluated before and during treatment. 3. Body weight, skin folds, hormones and lipids serum levels were not significantly affected by the treatment with Li. These results agree with previous reports of lack of effects of 1 month-Li administration on appetite and body weight in normal male subjects (Chen et al., 1992), and question the appropriateness of studying Li-induced obesity in healthy volunteers, given the short-term administration and low doses of Li that must be used.
Assuntos
Peso Corporal/efeitos dos fármacos , Hormônios Esteroides Gonadais/sangue , Carbonato de Lítio/farmacologia , Adulto , Análise de Variância , Índice de Massa Corporal , Peso Corporal/fisiologia , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Hidrocortisona/sangue , Lítio/sangue , Hormônio Luteinizante/sangue , Masculino , Prolactina/sangue , Radioimunoensaio , Valores de Referência , Reprodutibilidade dos Testes , Reprodução , Dobras Cutâneas , Testosterona/sangue , Hormônios Tireóideos/sangue , Tireotropina/sangue , Aumento de Peso/efeitos dos fármacosRESUMO
The efficacy of the antiviral agent Amantadine (AM, 5-100 mg/kg/sc, ip or intrahypothalamically, 12.5-100 micrograms bilaterally) in influencing body weight and food intake in drug-free rats, and in preventing neuroleptic-induced weight gain, was assessed in adult female rats. In drug-free rats, acute administration of systemic AM or directly injected in the lateral hypothalamus (LH) displayed a significant dose-dependent anorectic effect (p < 0.001). This effect could be mediated by the brain monoaminergic system, because systemic or local injections of AM increased dopamine and serotonin overflow in the nucleus accumbens and in the LH. Chronic administration of AM significantly decreased body weight gain in drug-free rats only at the dose of 100 mg/kg/sc. Similarly, obesity induced by the neuroleptic drug sulpiride (SUL, 20 mg/kg/ip for 21 days) was prevented by AM only at the dose of 100 mg/kg. AM did not prevent SUL-induced hyperprolactinemia, disruption of the vaginal cycle and a decrement in the weight of the uterus and ovaries at any dosage. This lack of efficacy of AM contrasts with that of bromocriptine, which completely prevented SUL-induced weight gain and hyperprolactinemia. The results show that despite a potent acute anorectic effect, AM displays a weak antagonistic action on SUL-induced obesity in rats, in contrast to the preliminary results obtained in humans. As AM metabolism differs in humans and rats, additional research is needed before its systematic testing in counteracting neuroleptic-induced obesity in patients with mental disorders.
Assuntos
Amantadina/uso terapêutico , Antipsicóticos/efeitos adversos , Obesidade/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Dopamina/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Estro/efeitos dos fármacos , Feminino , Hipotálamo/metabolismo , Núcleo Accumbens/metabolismo , Obesidade/induzido quimicamente , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Serotonina/metabolismo , Sulpirida/efeitos adversosRESUMO
Metabolic and endocrine abnormalities secondary to hyperprolactinemia, particularly hypogonadism, may be involved in the excessive body weight gain observed during treatment with antipsychotic drugs. The present study was conducted in healthy men in order to detect an endocrine imbalance secondary to antipsychotic drug administration, which, if sustained in the long term, might be involved in the development of obesity. Sulpiride (200 mg daily for 30 days) or placebo was nonblindly administered, and body weight gain was correlated with the serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, free testosterone, thyrotropic hormone, free tetraiodothyroxine, cortisol, dehydroepiandrosterone sulphate (DHEA-S), and the ratios estradiol/testosterone and testosterone/DHEA-S; the blood lipids were also assessed. Body weight gain and the serum levels of prolactin were significantly increased by sulpiride; in addition, a significant positive correlation was observed between prolactin levels and body weight gain. Other endocrine parameters were not significantly affected by the drug. These short-term results show that in healthy men, body weight can be increased by antipsychotic drug administration; this effect may be related to hyperprolactinemia alone, since other endocrine parameters were normal at the time of treatment. A more prolonged treatment with antipsychotic agents might be required to observe the alterations in gonadal and adrenal steroids often detected in subjects with primary obesity.
Assuntos
Antipsicóticos/efeitos adversos , Peso Corporal/efeitos dos fármacos , Doenças do Sistema Endócrino/induzido quimicamente , Prolactina/sangue , Sulpirida/efeitos adversos , Adulto , Hormônios Esteroides Gonadais/sangue , Gonadotropinas Hipofisárias/sangue , Humanos , Lipídeos/sangue , Masculino , Estado Nutricional , Hormônios Tireóideos/sangueRESUMO
Weight gain is an undesirable side-effect of long-term lithium administration which notably interferes with treatment compliance. The mechanisms of this weight gain remain unclear, making its management in patients difficult. In this paper, studies describing the features of this weight gain in patients and in rats treated with chronic lithium administration are reviewed. The effects of lithium on body weight differ between patients and rats in a number of ways, including the observation that excessive weight gain is observed in both male and female patients, but only in female rats. Nevertheless, an animal model of lithium-induced weight gain may be able to provide useful insights into some of the specific mechanisms involved, particularly those related to interactions with gonadal steroid function. We discuss the effects of lithium on the endocrine system, neurotransmitters, metabolism, electrolyte regulation, and feeding behavior, which might underlie lithium's effects on body weight. Finally, suggestions for the management of weight gain in the clinical setting are presented. These include, in the long term, dietary control and physical activity and, in the short term, choosing among several drugs that have been tested either in patients or in animal models of obesity. If weight gain still cannot be controlled and treatment compliance is at risk, the mood stabilizers carbamazepine or valproic acid might be substituted for lithium treatment.