Potentially hazardous drug interactions with psychotropics

Ben Chadwick is a specialist registrar in acute medicine at the Royal Hampshire County Hospital, Winchester. Derek Waller is a consultant physician and senior lecturer in medicine and clinical pharmacology at Southampton University Hospitals NHS Trust (Southampton General Hospital, Southampton SO16 6YD, UK. E-mail: derek.waller{at}suht.swest.nhs.uk). Guy Edwards is an emeritus consultant at Southampton University Hospitals NHS Trust and Visiting Professor at Prince of Songkla University, Hat Yai, Thailand. He has in the past received research grants and lecture fees from, and been invited to national and international meetings by, the manufacturers of several psychotropic drugs.

Of the many interactions with psychotropic drugs, a minority are potentially hazardous. Most interactions are pharmacodynamic, resulting from augmented or antagonistic actions at a receptor or from different mechanisms in the same tissue. Most important pharmacokinetic interactions are due to effects on metabolism or renal excretion. The major enzymes involved in metabolism belong to the cytochrome P450 (CYP) system. Genetic variation in the CYP system produces people who are ‘poor’, ‘extensive’ or ‘ultra-rapid’ drug metabolisers. Hazardous interactions more often result from enzyme inhibition, but the probability of interaction depends on the initial level of enzyme activity and the availability of alternative metabolic routes for elimination of the drug. There is currently interest in interactions involving uridine diphosphate glucuronosyltransferases and the P-glycoprotein cell transport system, but their importance for psychotropics has yet to be defined. The most serious interactions with psychotropics result in profound sedation, central nervous system toxicity, large changes in blood pressure, ventricular arrhythmias, an increased risk of dangerous side-effects or a decreased therapeutic effect of one of the interacting drugs.