Various combinations of drugs may be used to treat psychotic disorders, but pharmacodynamic and pharmacokinetic interactions can result in adverse effects. In most cases, interactions are of clinical significance only when drug therapy is initiated or discontinued, or when major changes in dosage are made. A number of patient‐related variables also affect the clinical significance of a drug‐drug interaction. To help predict the occurrence of interactions, and therefore minimize or prevent them, the clinician should be familiar with each agent's pharmacokinetics, the enzymes involved in its metabolism, and the expected pharmacologic effects. With this knowledge, the clinician may consider decreasing the dosage of previous therapy or reducing the dosage of a coadministered drug to prevent or minimize the potential of an adverse interact