Improved Antidepressant Remission in Major Depression via a Pharmacokinetic Pathway Polygene Pharmacogenetic Report

Objective: Major depressive disorder (MDD) is projected to be a leading cause of disability globally by 2030. Only a minority of patients remit with antidepressants. If assay of polymorphisms influencing central nervous system (CNS) bioavailability could guide prescribers to more effectively dose patients, remission rates may improve and the burden of disease from MDD reduce. Hepatic and blood brain barrier (BBB) polymorphisms appear to influence antidepressant CNS bioavailability. Methods: A 12 week prospective double blind randomized genetically guided versus unguided trial of antidepressant dosing in Caucasian adults with MDD (n=148) was conducted. Results: Subjects receiving genetically guided prescribing had a 2.52-fold greater chance of remission (95% confidence interval [CI]=1.71-3,73, z=4.66, p<0.0001). The number needed to genotype (NNG)=3 (95% CI=1.7-3.5) to produce an additional remission. Conclusion: These data suggest that a pharmacogenetic dosing report (CNSDose (R)) improves antidepressant efficacy. The effect size was sufficient that translation to clinical care may arise if results are independently replicated.