The Association Between COMT Genotype and Bupropion Treatment Response in Outpatients With Major Depressive Disorder

Background: Studies examining treatment responses to antidepressants based on genotype have produced inconsistent findings. Although catechol-O-methyltransferase (COMT) metabolizes catecholamines, pharmacodynamic association of COMT genotypes in treating major depressive disorder (MDD) has limited study. This naturalistic study of outpatients with MDD examined the relationship between COMT genotypes and treatment responses to bupropion, a widely used norepinephrine-dopamine reuptake inhibitor.

Methods: Participants were 241 adult outpatients at one Midwestern psychopharmacology clinic who met the DSM-5 criteria for MDD and had available genetic testing results (Genomind’s Genecept Assay® v2.0) between February 2016 and January 2017. We used retrospective chart reviews to gather 1) demographic data, 2) COMT genotype (dichotomized as VAL carriers [Met/Val, Val/Val] or Met/Met), 3) Patient Health Questionnaire (PHQ-9) scores at each clinic visit (M = 3.8 visits, SD = 1.5, range = 1-10), and 4) bupropion doses (no bupropion, < 200 mg [low dose], or 200 - 450 mg [high dose]).

Results: Tests for response differences by bupropion dose showed that for Val carriers, high bupropion doses resulted in significantly greater declines in PHQ-9 scores than no bupropion (t(868)=5.04, p < 0.0001) or low dose bupropion (t(868)=3.29, p = 0.001). Additionally, Val carriers differed significantly compared to Met/Met patients in response to high dose bupropion (t(868)=-2.03, p=0.04), but not to low dose bupropion.

Conclusions: High-dose bupropion benefits MDD patients with Met/Val or Val/Val COMT genotypes, but not patients with Met/Met genotype. Prospective studies are necessary to replicate this pharmacodynamic relationship between bupropion and COMT genotypes and explore economic and clinical outcomes.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.