The Potential for Clinically Significant Drug-Drug Interactions Involving the CYP 2D6 System: Effects with Fluoxetine and Paroxetine versus Sertraline

VA patients on fluoxetine, paroxetine, and sertraline were equally likely to be on drugs whose metabolism is dependent on CYP 2D6, including drugs with narrow therapeutic indices. No differences were found in doses of tricyclic antidepressants (i.e., "victim" drugs), which have narrow therapeutic indices and serious dose-dependent toxicity, when co-prescribed with fluoxetine or paroxetine versus sertraline (i.e., "perpetrator" drugs), despite predictable differences in CYP 2D6-mediated clearance of these drugs.