Clinical associations with treatment resistance in depression: An electronic health record study.

Treatment resistance is common in major depressive disorder (MDD), yet clinical risk factors are not well understood. Using a discovery-replication design, we conducted phenome-wide association studies (PheWASs) of MDD treatment resistance in two electronic health record (EHR)-linked biobanks. The PheWAS included participants with an MDD diagnosis in the EHR and at least one antidepressant (AD) prescription. Participant lifetime diagnoses were mapped to phecodes. PheWASs were conducted for three treatment resistance outcomes based on AD prescription data: number of unique ADs prescribed, ≥1 and ≥2 CE switches. Of the 180 phecodes significantly associated with these outcomes in the discovery cohort (n = 12,558), 71 replicated (n = 8,206). In addition to identifying known clinical factors for treatment resistance in MDD, the total unique AD prescriptions was associated with additional clinical variables including irritable bowel syndrome, gastroesophageal reflux disease, symptomatic menopause, and spondylosis. We calculated polygenic risk of specific-associated conditions and tested their association with AD outcomes revealing that genetic risk for many of these conditions is also associated with the total unique AD prescriptions. The number of unique ADs prescribed, which is easily assessed in EHRs, provides a more nuanced measure of treatment resistance, and may facilitate future research and clinical application in this area.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Mann receives royalties for commercial use of the C-SSRS from the Research Foundation for Mental Hygiene and from Columbia University from sales of the Columbia Pathways app. Dr. Weissman has received funding from NIMH and Columbia University Institute for Developmental Sciences and receives book royalties from Perseus Press and Oxford Press. None of these represent a conflict of interest. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)