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Predicting response to antipsychotic treatment might optimize treatment strategies in early phases of schizophrenia. We aimed to investigate sociodemographic, premorbid and clinical predictors of response to antipsychotic treatment after a first episode of non-affective psychosis.375 (216 males) patients with a diagnosis of non affective psychosis entered the study. The main outcome measure was clinical response at 6 weeks and variables at baseline were evaluated as predictors of response. ANOVA for continuous and chi-square for categorical data were used to compare responders and non-responders. Multivariate logistic regression was used to establish a prediction model.53.3% of study subjects responded to antipsychotic treatment. The following variables were associated with an unfavorable response:1. — lower severity of symptoms at baseline;2. — diagnosis of schizophrenia;3. — longer DUI and DUP;4. — poorer premorbid adjustment during adolescence and adulthood;5. — family history of psychosis, and 6. — hospitalization. Patients with a family history of psychosis, longer DUP, poor premorbid functioning and lower severity of psychotic symptoms at intake have a reduced likelihood of responding to antipsychotic treatment.Helping clinicians to identify those first episode patients with a lower probability of having a favorable clinical response is meant as a first step to achieve a successful initial treatment.