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Body weight gain induced by antipsychotic drugs: mechanisms and management.<\/jats:p><jats:p>Acta Psychiatrica Scand 1999: <jats:bold>100<\/jats:bold>: 3\u201316. \u00a9 Munksgaard 1999.<\/jats:p><jats:p>Long\u2010term administration of typical and atypical antipsychotic drugs (AP) induces excessive weight gain which afflicts up to 50% of patients, impairs health and interferes with treatment compliance. Basic and clinical research has shown that AP may affect body weight through diverse mechanisms. Increased appetite is probably related to the interaction of AP with neuronal receptors to dopamine, serotonin and histamine. Additional metabolic\u2010endocrine disruption of weight regulation may be related to the effects of AP\u2010induced hyperprolactinaemia on gonadal\u2010adrenal steroids and insulin sensitivity. In humans, programmed physical activity, dietary restriction, anorectic agents, and drugs that counteract hyperprolactinaemia have been shown to be successful in a limited number of studies. Two novel strategies could expand the available therapeutic options. First, in preclinical experiments in female rats the estradiol antagonist\/agonist drug tamoxifen or estradiol itself have been shown to completely prevent the obesity provoked by the AP sulpiride, and to induce an endocrine\u2010metabolic milieu that seems to counteract AP\u2010induced obesity. Secondly, it has also been shown that oral antihyperglycaemic agents such as metformin may decrease body weight and counteract insulin resistance and hyperinsu\u2010linaemia which is correlated with several metabolic abnormalities in obese subjects. Lastly, estradiol replacement, tamoxifen and\/or antihyperglycaemic agents are not devoid of significant side\u2010effects, and these drugs have not been tested in obese psychiatric patients. 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