TY - JOUR
T1 - Association Between Polygenic Risk Scores and Treatment Response to Antidepressants, Benzodiazepines, and Antihistamines in Anxiety and Depression
AU - Markant, Amelie
AU - Tabrizi, Fara
AU - Grönvall, Hampus
AU - Speed, Doug
AU - Åhs, Fredrik
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/5
Y1 - 2025/5
N2 - BACKGROUND: Anxiety and depression are the most prevalent mental health disorders. The first-line treatment is antidepressants, such as serotonin reuptake inhibitors, but benzodiazepines and antihistamines are also used to treat anxiety. Only one-third of patients achieve remission with first-line treatment. Identifying responders and nonresponders to monotherapy prior to treatment could increase remission rates and reduce dropout. The aim of the current study was to predict response to antidepressants, benzodiazepines, and antihistamines from polygenic risk scores (PRSs) in individuals with anxiety and/or depression symptoms.METHODS: We identified 2515 individuals in a genotyped cohort in the Swedish Twin Registry who had been prescribed drugs for anxiety and/or depression. Of these individuals, 1037 received monotherapy (555 with antidepressants, 169 with benzodiazepines, and 313 with antihistamines). The remaining 1478 individuals switched or added more drugs during the assessment period (2005-2018). The accuracy of 42 PRSs for psychiatric diagnoses as well as for nonclinical phenotypes in predicting mono- versus multitherapy was assessed using logistic regression.RESULTS: Monotherapy with benzodiazepines was predicted by a PRS for depressive symptoms indexed by the Patient Health Questionnaire (odds ratio [OR] = 1.29), while monotherapy with antihistamines was predicted by a PRS for lifetime anxiety disorder (OR = 1.25) and a PRS for schizophrenia (OR = 1.24). None of the investigated PRSs significantly predicted monotherapy with antidepressants.CONCLUSIONS: Real-world data suggest that monotherapy with benzodiazepines or antihistamines can be predicted from PRSs related to anxiety, depression, and schizophrenia.
AB - BACKGROUND: Anxiety and depression are the most prevalent mental health disorders. The first-line treatment is antidepressants, such as serotonin reuptake inhibitors, but benzodiazepines and antihistamines are also used to treat anxiety. Only one-third of patients achieve remission with first-line treatment. Identifying responders and nonresponders to monotherapy prior to treatment could increase remission rates and reduce dropout. The aim of the current study was to predict response to antidepressants, benzodiazepines, and antihistamines from polygenic risk scores (PRSs) in individuals with anxiety and/or depression symptoms.METHODS: We identified 2515 individuals in a genotyped cohort in the Swedish Twin Registry who had been prescribed drugs for anxiety and/or depression. Of these individuals, 1037 received monotherapy (555 with antidepressants, 169 with benzodiazepines, and 313 with antihistamines). The remaining 1478 individuals switched or added more drugs during the assessment period (2005-2018). The accuracy of 42 PRSs for psychiatric diagnoses as well as for nonclinical phenotypes in predicting mono- versus multitherapy was assessed using logistic regression.RESULTS: Monotherapy with benzodiazepines was predicted by a PRS for depressive symptoms indexed by the Patient Health Questionnaire (odds ratio [OR] = 1.29), while monotherapy with antihistamines was predicted by a PRS for lifetime anxiety disorder (OR = 1.25) and a PRS for schizophrenia (OR = 1.24). None of the investigated PRSs significantly predicted monotherapy with antidepressants.CONCLUSIONS: Real-world data suggest that monotherapy with benzodiazepines or antihistamines can be predicted from PRSs related to anxiety, depression, and schizophrenia.
KW - Anxiolytics
KW - Nonselective monoamine reuptake inhibitors
KW - Receiver operating characteristic curve
KW - Selective serotonin reuptake inhibitors
KW - Treatment-resistant
UR - http://www.scopus.com/inward/record.url?scp=105000738701&partnerID=8YFLogxK
U2 - 10.1016/j.bpsgos.2025.100470
DO - 10.1016/j.bpsgos.2025.100470
M3 - Journal article
C2 - 40213705
SN - 2667-1743
VL - 5
JO - Biological Psychiatry: Global Open Science
JF - Biological Psychiatry: Global Open Science
IS - 3
M1 - 100470
ER -