Clinically significant interactions with antipsychotics

Second-generation antipsychotics (SGAs) have become the mainstay of treatment for patients with schizophrenia and bipolar disorder. The antipsychotic drugs are often prescribed with other medications to improve clinical efficacy or treat comorbid diseases. Drug combinations can cause pharmacokinetic and/or pharmacodynamic drug-drug interactions. Pharmacokinetic interactions can occur during any pharmacokinetic phases, absorption, distribution, metabolism, or excretion. Smoking, caffeine, and food might have influences on the pharmacokinetic profiles of SGAs. Pharmacodynamic drug-drug interactions occur when drugs act at the same or interrelated sites of action, resulting in additive, synergistic, or antagonistic effects of each drug. Among the genes involved in pharmacokinetics, the members of cytochrome P450 family display large interindividual and interethnic variations in activity. Other enzyme systems such as UDP-glucuronosyltransferases also exhibit genetic polymorphism with potential clinical relevance in psychopharmacology. The demographic characteristics might also have impact on pharmacokinetic and/or pharmacodynamic profiles of SGAs. The potential pharmacokinetic interactions would guide antipsychotic dosage adjustments. For antipsychotics, optimal dose titration should be guided by measuring plasma concentrations. Therapeutic drug monitoring (TDM) is a valid tool for tailoring the dosage of antipsychotic drugs. Clinicians must have the knowledge of potential interactions of SGAs and carefully monitor patients to minimize potentially adverse events and maximize therapeutic efficacy.