Comparison of potential psychiatric drug interactions in six drug interaction database programs: A replication study...

Drug interaction database programs are a fundamental clinical tool. In 2018, we compared the category of potential drug-drug interaction (DDI) provided by six drug interaction database programs for 100 drug interaction pairs including psychiatric drugs, and found the category often differed. This study replicated the comparison in 2020 after 2 years of updates to all six drug interaction database programs.

The 100 drug pairs included 94 different drugs: 67 pairs with a psychiatric and non-psychiatric drug, and 33 pairs with two psychiatric drugs. The assigned category of potential DDI for the drug pairs was compared using percent agreement and Fleiss kappa statistic of interrater reliability.

Despite 67 updates involving 46 of the 100 drug pairs, differences remained. The overall percent agreement among the six drug interaction database programs for the category of potential DDI was 67%. The interrater agreement results did not change. The Fleiss kappa overall interrater agreement was fair. The kappa agreement for a drug pair with any severe category rating was substantial, and the kappa agreement for a drug pair with any major category rating was fair.

Physicians should be aware of the inconsistency among drug interaction database programs in the category of potential DDI for drug pairs including psychiatric drugs. Additionally, the category of potential DDI for a drug pair may change over time. This study highlights the importance of ongoing international efforts to standardize methods used to define and classify potential DDI.