Pharmacogenetics to Personalize Dosing of Tricyclic Antidepressants in Major Depressive Disorder: A Randomized Clinical Trial (PITA study)

Introduction Tricyclic antidepressants (TCAs) have an important role in pharmacotherapy of Major Depressive Disorder (MDD). TCA dosing is aimed at achieving a concentration the therapeutic window. Due to inter-individual differences activity Cytochrome P450 (CYP) 2D6 and 2C19, (enzymes involved metabolism) patients require individualized dose. Currently, finding suitable dosage process trial-and-error, including multiple drug measurements dose adjustments. A starting based on patient CYP2D6 CYP2C19 metabolizer phenotype may contribute more quickly, possibly resulting higher treatment efficacy occurrence fewer adverse effects. Objectives We study whether genotype-informed TCAs leads faster attainment plasma concentrations, reduction depression severity symptoms less Methods conducted double-blind randomized clinical trial, which (18-65 years) diagnosed with severe MDD eligible for were two arms: The intervention arm (Pharmacogenetics Informed Treatment; PIT) standard (Treatment As Usual; TAU). Patients treated nortriptyline, clomipramine or imipramine seven weeks depressive symptom effects monitored weekly. primary outcome measure, time needed attain concentration, was analyzed using Kaplan-Meier analyses. secondary measures, effects, mixed model linear regression. Results In total, we 111 patients. PIT group (n=56) reached significantly (Kaplan Meier, X2 (1) = 4.3, p=0.039) compared TAU (n=55), especially nortriptyline. On average decreased relatively than TAU, although this not different: F(6) 0.45, p 0.84. events during period differed between (F(6)=3.10, p=0.008). experienced last study. Conclusions Genotype-informed concentrations does lead Although able demonstrate that better response, conclude pharmacogenetics can optimization pharmacological treatment. Future research focus subgroups be great value, such as specific abnormal pharmacogenetic profile. Disclosure Interest None Declared