Drug–Drug Interactions Associated with Second-Generation Antipsychotics: Considerations for Clinicians and Patients

While not always clinically significant, patients with schizophrenia may be at risk for drug–drug interactions (DDIs) with second-generation antipsychotics. Second-generation antipsychotics are increasingly being used in a broader population of patients and, therefore, for those with comorbid illnesses, adjunctive treatments, or other diagnoses, the clinical significance of DDIs is increasing. This paper reviews currently available data concerning DDIs that occur between second-generation antipsychotics and other medications or substances when metabolized by the cytochrome P-450 (CYP) family of enzymes. This review will assess the clinical relevance of these interactions for physicians and patients with schizophrenia. Methods: EMBASE and MEDLINE searches were conducted (no date restrictions) using the keywords “drug–drug interactions,” “atypical antipsychotics,” “olanzapine,” “ziprasidone,” “quetiapine,” “risperidone,” “aripiprazole,” “clozapine,” “asenapine,” “bifeprunox,” and “paliperidone.” Principal observations: Second-generation antipsychotics are primarily metabolized by CYP enzymes. When coadministered with inducers or inhibitors (psychotropic or non-psychotropic medications or substances) of CYP enzymes, antipsychotic plasma levels may be reduced or increased, respectively, as a result of DDIs. This can result in reduced effectiveness of the antipsychotic or an increased risk of adverse events, respectively. Drugs with a less clinically significant risk for DDIs are a more reliable treatment option for patients in whom drug plasma levels may fluctuate. Conclusion: Some of the currently available second-generation antipsychotics have a higher potential for DDIs. Agents with a reduced liability for DDIs may be safer treatments, as the systemic drug concentration is less likely to seriously increase or decrease when other medications are knowingly or inadvertently co-prescribed or when hepatic problems and drug abuse are present. Psychopharmacology Bulletin. 2007;40(1):77-97.