Objective. To investigate the effects of a selective serotonin reuptake inhibitor (SSRI) on the neuroendocrine and autonomic nervous system perturbations found in abdominal obesity.Design. Treatment for 6 months with citalopram and for 6 months with placebo using a double-blind, cross-over design, with a 2-month wash-out period between treatment periods.Subjects. Sixteen healthy men, 45-60 years, moderately obese and with an abdominal fat distribution.Measurements. Anthropometry, three different depression rating scales, serum lipids, testosterone, IGF-I, oral glucose tolerance test (OGTT), pituitary stimulation with corticotropin releasing hormone (CRH), arithmetic stress test, and excretion of cortisol and metoxycatecholamines in urine, collected during 24 h.Results. Cortisol concentrations in the morning were low before treatment, indicating a perturbed function of the hypothalamic-pituitary-adrenal (HPA) axis. After treatment with citalopram morning cortisol concentrations rose to normal. Cortisol concentrations after stimulation with CRH or stress were elevated by citalopram treatment, but urinary cortisol excretion was unchanged. The glucose concentrations after OGTT (120 min) tended to be reduced, with unchanged insulin concentrations, whilst other metabolic values did not change during treatment. Heart rate after administration of CRH, and during laboratory stress test, decreased by treatment with citalopram. Diurnal urinary excretion of metoxycatecholamines tended to decrease. Neither body mass index nor waist/hip circumference ratio decreased. Depression scores were within normal limits before treatment and did not change.Conclusion. The results of this pilot study indicate improvements in the regulation of neuroendocrine-autonomic systems as well as metabolism in abdominal obesity during treatment with an SSRI.