Unstable anticoagulation in the course of amitriptyline treatment

A potential drug-drug interaction between the tricyclic antidepressant amitriptyline and the oral anticoagulant phenprocoumon, causing intensified hypo- and/or hyperprothrombinemic effects, was investigated. In seven patients simultaneously receiving amitriptyline and phenprocoumon the course of the Quick values and the amitriptyline and phenprocoumon dosages were registered. The resulting data represented graphically was additionally compared with data and diagrams gained from a control group of seven phenprocoumon patients not receiving amitriptyline. Whereas in the control group the average Quick values (or the target International Normalized Ratio) lay within the required therapeutic range, massive fluctuations were seen in the amitriptyline-treated patients. These fluctuations did not disappear until the amitriptyline medication was discontinued. Whether our findings are actually due to a clinically relevant drug-drug interaction needs to be investigated in further controlled studies based on a larger number of patients, the more so as no comparable investigations and only few references to this subject are to be found in the literature. Should an amitriptyline influence on the frequently prescribed coumarin derivative be proven, an increased risk of rethrombosis or bleeding complications in patients receiving both amitriptyline and phenprocoumon would appear to be indicated.