BACKGROUND: Pharmacodynamics and pharmacogenetics are being explored in pharmacological treatment response for major depressive disorder (MDD). Interactions between genotype and treatment response may be dose dependent. In this study, we examined whether MDD patients with Met/Met, Met/Val, and Val/Val COMT genotypes differed in their response to bupropion in terms of depression scores.

METHODS: This study utilized a convenience sample of 241 adult outpatients (≥18 years) who met DSM-5 criteria for MDD and had visits at a Midwest psychopharmacology clinic between February 2016 and January 2017. Exclusion criteria included various comorbid medical, neurological, and psychiatric conditions and current use of benzodiazepines or narcotics. Participants completed genetic testing and the 9 question patient-rated Patient Health Questionnaire (PHQ-9) at each clinic visit (M = 3.8 visits, SD = 1.5) and were prescribed bupropion or another antidepressant drug. All participants were adherent to pharmacotherapy treatment recommendations for >2 months following genetic testing.

RESULTS: Participants were mostly Caucasian (85.9%) outpatients (154 female and 87 male) who were 44.5 years old, on average (SD = 17.9). For Val carriers, high bupropion doses resulted in significantly lower PHQ-9 scores than no bupropion (t(868) = 5.04, p < .001) or low dose bupropion (t(868) = 3.29, p = .001). Val carriers differed significantly from Met/Met patients in response to high dose bupropion (t(868) = -2.03, p = .04), but not to low dose bupropion.

CONCLUSION: High-dose bupropion is beneficial for MDD patients with Met/Val or Val/Val COMT genotypes, but not for 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.

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Brain Behav

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