Weight gain is a frequent and important side effect of psychotropic treatment. We sought to determine weight change predictors during treatment with antidepressant drugs. In 24 patients weight, plasma levels of leptin, tumor necrosis factor-alpha (TNF-alpha and soluble TNF receptors were determined longitudinally and a multiple linear regression analysis was used to predict weight change from baseline to the sixth week of treatment. Changes of weight during the first week of treatment, but no other parameter, strongly predicted weight change until endpoint (adjusted R2 = 0.68, F = 50.45, df = 1,23, p < 0.001). Very early changes in weight during treatment with psychotropic drugs might be a simple and clinically useful predictor of future weight development.