Genetic and Phenotypic Associations With Sustained Antidepressant Use in Major Depressive Disorder

Can real-world antidepressant prescription patterns identify biologically meaningful subtypes of major depressive disorder (MDD) and inform precision psychiatry approaches?In this cohort study of 12 074 participants, MDD subgroups defined by sustained single-drug antidepressant use (≥360 days) had distinct phenotypic profiles; polygenic scores for psychiatric disorders differentiated individuals with greater class diversity but not single-drug sustained-use 360 groups. One genome-wide significant immune-related variant in / was associated with sustained selective serotonin reuptake inhibitor use.The findings suggest that real-world antidepressant prescription patterns have the potential to identify phenotypically distinct MDD subtypes that may guide personalized treatment selection, and polygenic scores may help identify which patients are at risk of difficult-to-treat depression.

Corresponding Author: Naomi R. Wray, PhD, Department of Psychiatry, Warneford Hospital, University of Oxford, Warneford Lane, Headington, Oxford OX3 7JX, United Kingdom (naomi.wray@psych.ox.ac.uk).

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