OBJECTIVES: While pharmacological hepatic interaction mechanisms for antipsychotics are largely known, there is little research so far on the prevalence of potential interactions with other substances. The objective of the present study is to estimate the annual prevalence of potential pharmacokinetic drug-drug interactions (DDIs) between antipsychotic and non-antipsychotic therapies in patients with schizophrenia. METHODS: A retrospective analysis of drug prescriptions for patients treated for schizophrenia (ICD-10 codes F20 - F29) was performed using the German IMS Disease Analyzer data for psychiatrists for 2007. These data originate from electronic medical records from a representative panel of German psychiatrists, and include drug prescriptions and medical diagnoses. Potential antipsychotic drug-drug interactions based on cytochrome P450 metabolism (1A2, 2D6, 3A4, and 3A pathways) for antipsychotics and corresponding interacting drugs (pathway inducers and inhibitors) were identified based on literature and drug information resources. A potential DDI was identified when combinations known to interact had 20 or more days of overlap, determined by prescription dates, dosing information and pack size. Incidence of overlap was calculated by antipsychotic, metabolic pathway and interaction mechanism. RESULTS: A total of 5449 patients received an atypical antipsychotic. The most frequent interaction mechanisms were inhibition of CYP2D6 and of CYP3A4: between 38% and  45% of the patients treated with atypicals had a 20 day-overlap with inhibitors of CYP2D6, and 17% to 26% with CYP3A4-Inhibitors. Potential interactions were most commonly associated with antidepressants.  CONCLUSIONS: The risk of potential DDI in schizophrenia patients treated with antipsychotics in Germany is common, mainly due to concomitant prescription of antipsychotics and antidepressants. The reported estimates are based on real world data for psychiatrists in Germany, and are conservative, since drugs prescribed by other physicians or bought over the counter could not be taken into account.