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Introduction of second-generation antipsychotics (SGAs) has reduced neurologic toxicity but are associated with increased weight gain and obesity. The objective of this pilot study is to compare the effects of first-generation antipsychotics (FGAs) and SGAs in patients with schizophrenia on body fat and presumed concomitant metabolic parameters.Study compared schizophrenia nondiabetic men treated with FGAs (group 1, n = 5) and men treated with SGAs (group 2, n = 9). Each subject completed psychiatric and endocrine evaluation including severity of psychiatric symptoms, adverse effects, body weight, body composition, and measurements of glucose, insulin, adipokines, and inflammatory markers. Student t test was used for statistical analysis.Men treated with FGAs had a lower mean body mass index with a trend toward statistical significance (25.3 ± 1.4 vs 29.3 ± 1.7, P = 0.06). Treatment with FGAs was associated with lower waist/height ratio (0.55 ± 0.02 vs 0.62 ± 0.02, P = 0.036) and android fat mass index (0.62 ± 0.01 vs 0.96 ± 0.1, P = 0.03). Homeostasis Model Assessment for insulin resistance values were suggestive of significantly lower peripheral insulin resistance in men treated with FGAs (0.92 ± 0.15 vs 2.3 ± 0.34, P = 0.014).The results of this study are significant for decreased peripheral insulin resistance in men treated with SGAs in a setting of no significant age difference and only a trend toward higher body mass index, but consistent documentation of increased abdominal fat by 3 different methodologies. Future studies involving larger number of subjects are warranted to verify the present findings.