There is only limited community-based practice safety information available regarding antidepressant use in pediatric patients. This study identifies the factors associated with incident neuroendocrine-related metabolic, digestive, and sexual/reproductive adverse events in children and adolescents treated with antidepressants. A retrospective cohort design evaluating Medicaid medical and pharmacy claims between January, 1996 and December, 2005 was employed for 11970 children and adolescents prescribed an antidepressant medication, and a random sample of 4500 children not treated with psychotropic medications. Incident obesity/weight gain, Type 2 diabetes mellitus, and dyslipidemia were more likely for those prescribed selective serotonin reuptake inhibitors (SSRIs) (OR = 1.49; 1.37; 1.44), whereas Type 2 diabetes mellitus and dyslipidemia were more likely for those prescribed weight-inducing antidepressants (ORs = 1.26; 1.24), and those with pre-existing endocrinopathies (ORs = 3.96; 1.90), controlling for the effects of co-prescribed mood stabilizers or antipsychotics. Incident nausea/vomiting was less likely for those taking SSRIs (OR = 0.78). Females and children under 12 years of age were more likely to develop these adverse effects. Practitioners need to carefully consider the neuroendocrine- related adverse effects of SSRI antidepressant agents in particular, especially in individuals with comorbid endocrine conditions, and those co-prescribed other classes of psychotropic medications.