During a first episode of psychosis, treatment with antipsychotic drugs can improve both positive and negative symptoms. If sufficient amelioration does not occur, adding psychotropic comedication may result in a favorable outcome. To establish sex differences in psychotropic comedication use, we conducted an exploratory retrospective study among first-break patients diagnosed with schizophrenia or schizophreniform disorder. Concerning patient characteristics, no difference in age or antipsychotic drug use was established. At admission, men significantly more often had comorbid substance abuse. Analysis showed that significantly more women than men received benzodiazepines after the onset of psychosis (OR 1.92, 95% CI 1.13-1.27). No sex difference was found in antidepressant comedication (OR 1.22, 95% CI 0.48-3.11). We established a definite sex difference in concomitant benzodiazepine use in first-break patients with schizophrenia. Since women have a better prognosis, we suggest further research to evaluate the efficacy and safety of early benzodiazepine use in the course of schizophrenia. Furthermore, we recommend investigating the possible correlation between benzodiazepine use and substance abuse as a way of treating premorbid symptoms of schizophrenia.