Evaluating the clinical significance of drug interactions: a systematic approach

Remembering the myriad of psychotropic drug interactions is extremely difficult. Nevertheless, by applying a systematic approach, the clinician can often predict the occurrence and time course of such interactions. Several factors must be considered when assessing the potential consequences. Drug-related factors that increase the risk for clinically significant interactions include a low therapeutic index or narrow therapeutic window, a multiplicity of pharmacological actions, and inhibition or inducement of cytochrome P450 enzymes. Next, patient-related factors that can increase the risk for significant drug interactions should be considered. These include genetically based variations in drug-metabolizing capacity, as well as advanced age, underlying medical illness, and comorbid substance abuse. Finally, the literature should be carefully reviewed to as-certain the potential clinical relevance of available data. If a clinically significant drug interaction appears likely to occur, the patient's clinical status should be followed closely; therapeutic drug monitoring should be used if applicable and dosage adjustments made accordingly. Rational polypharmacy requires an understanding of the pharmacological principles governing drug interactions and a knowledge of the factors that increase the likelihood of clinically significant variations in drug action. This will allow the clinician to maximize beneficial effects while minimizing the risk of adverse events.