Abstract: The use of antipsychotic drugs has started a new era in the treatment of psychotic disorders. Nevertheless, they cause complications in the long-term treatment, which is mainly weight gain. In this study, we investigated circulating levels of hypothalamic neuropeptides, which are related to appetite regulation, neuropeptide Y (NPY), α-melanocyte-stimulating hormone (α-MSH), cocaine- and amphetamine-regulated transcript (CART), and leptin, in first-attack psychotic patients who were treated with an atypical antipsychotic drug, risperidone, for 4 weeks. We used a case-control association design to compare the neuropeptides in the control group versus before and after treatment of the patient group. Samples were obtained from psychotic patients who were admitted to the Psychiatry Outpatient Clinics, Gulhane School of Medicine, Ankara, Turkey. When compared with the control group, NPY and α-MSH plasma levels of psychotic patients were severely reduced, and the CART levels were substantially increased when they were first diagnosed (before treatment). However, the patients’ body mass index and circulating leptin levels were markedly high after the treatment. Circulating levels of those neurohormones were not significantly changed between before and after treatment of the patients. These data demonstrate that peripheral α-MSH and NPY, although reflecting only secretion from peripheral organs, nevertheless, may provide an insight into the patients sympathetic tone and also suggest change of their appetite regulation. α-Melanocyte-stimulating hormone, NPY, and CART plasma levels may be used as a predictor of weight gain in the early treatment of the patients along with the leptin levels.