OBJECTIVE The objective of this prospective, naturalistic study, conducted in first-episode psychosis patients from a Central-European population, was to assess the utility of Cytochrome P-450 2D6 (CYP2D6) genotype testing under normal clinical setting. METHODS A total of 35 patients diagnosed for the first time with schizophrenia or acute schizophrenia-like psychotic disorder and treated with risperidone were enrolled in the study. These patients underwent sequentiation of the CYP2D6 gene and evaluations of symptoms and severity of adverse effects using the PANSS and UKU scales, respectively. Doses of antipsychotics and other co-medication were monitored as well. In statistical analysis, Fisher's exact test was used to compare ratios and the Wilcoxon rank-sum test was used in the comparison of continual variables. RESULTS PM patients showed a significantly lower reduction in psychotic symptoms and a greater severity of psychotic symptoms following risperidone treatment and higher doses of antipsychotics not metabolized by CYP2D6, which were used as co-medication. CONCLUSIONS Based on these results, patients with the PM genotype experiencing first-episode schizophrenia don't appear to be optimal recipients of risperidone treatment. However, as the main limitation of this study was the relatively small sample-size, replication with a larger scale study is needed to confirm these findings.