Association Between Polygenic Risk Scores and Treatment Response to Antidepressants, Benzodiazepines, and Antihistamines in Anxiety and Depression

Amelie Markant; Fara Tabrizi; Hampus Grönvall; Doug Speed; Fredrik Åhs

doi:10.1016/j.bpsgos.2025.100470

Association Between Polygenic Risk Scores and Treatment Response to Antidepressants, Benzodiazepines, and Antihistamines in Anxiety and Depression

Amelie Markant^*, Fara Tabrizi, Hampus Grönvall, Doug Speed, Fredrik Åhs

^*Corresponding author for this work

Center for Quantitative Genetics and Genomics

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

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.

Original language	English
Article number	100470
Journal	Biological Psychiatry: Global Open Science
Volume	5
Issue	3
Number of pages	9
ISSN	2667-1743
DOIs	https://doi.org/10.1016/j.bpsgos.2025.100470
Publication status	Published - May 2025

Keywords

Anxiolytics
Nonselective monoamine reuptake inhibitors
Receiver operating characteristic curve
Selective serotonin reuptake inhibitors
Treatment-resistant

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@article{e5297652b4d142ffb84ba84d1520755b,

title = "Association Between Polygenic Risk Scores and Treatment Response to Antidepressants, Benzodiazepines, and Antihistamines in Anxiety and Depression",

abstract = "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.",

keywords = "Anxiolytics, Nonselective monoamine reuptake inhibitors, Receiver operating characteristic curve, Selective serotonin reuptake inhibitors, Treatment-resistant",

author = "Amelie Markant and Fara Tabrizi and Hampus Gr{\"o}nvall and Doug Speed and Fredrik {\AA}hs",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = may,

doi = "10.1016/j.bpsgos.2025.100470",

language = "English",

volume = "5",

journal = "Biological Psychiatry: Global Open Science",

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Association Between Polygenic Risk Scores and Treatment Response to Antidepressants, Benzodiazepines, and Antihistamines in Anxiety and Depression. / Markant, Amelie; Tabrizi, Fara; Grönvall, Hampus et al.
In: Biological Psychiatry: Global Open Science, Vol. 5, No. 3, 100470, 05.2025.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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

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

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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 -

Association Between Polygenic Risk Scores and Treatment Response to Antidepressants, Benzodiazepines, and Antihistamines in Anxiety and Depression

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