TY - JOUR
T1 - Clinical associations with treatment resistance in depression
T2 - An electronic health record study
AU - Coombes, Brandon J.
AU - Sanchez-Ruiz, Jorge A.
AU - Fennessy, Brian
AU - Pazdernik, Vanessa K.
AU - Adekkanattu, Prakash
AU - Nuñez, Nicolas A.
AU - Lepow, Lauren
AU - Melhuish Beaupre, Lindsay M.
AU - Ryu, Euijung
AU - Talati, Ardesheer
AU - Mann, J. John
AU - Weissman, Myrna M.
AU - Olfson, Mark
AU - Pathak, Jyotishman
AU - Charney, Alexander W.
AU - Biernacka, Joanna M.
N1 - Publisher Copyright:
© 2024
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - Antidepressants
KW - Comorbidity
KW - MDD
KW - PRS
KW - PheWAS
KW - TRD
UR - http://www.scopus.com/inward/record.url?scp=85204673161&partnerID=8YFLogxK
U2 - 10.1016/j.psychres.2024.116203
DO - 10.1016/j.psychres.2024.116203
M3 - Article
AN - SCOPUS:85204673161
SN - 0165-1781
VL - 342
JO - Psychiatry Research
JF - Psychiatry Research
M1 - 116203
ER -