TY - JOUR
T1 - Metabolizing status of CYP2C19 in response and side effects to medications for depression
T2 - Results from a naturalistic study
AU - Calabrò, Marco
AU - Fabbri, Chiara
AU - Kasper, Siegfried
AU - Zohar, Joseph
AU - Souery, Daniel
AU - Montgomery, Stuart
AU - Albani, Diego
AU - Forloni, Gianluigi
AU - Ferentinos, Panagiotis
AU - Rujescu, Dan
AU - Mendlewicz, Julien
AU - De Ronchi, Diana
AU - Serretti, Alessandro
AU - Crisafulli, Concetta
N1 - Publisher Copyright:
© 2022
PY - 2022/3
Y1 - 2022/3
N2 - Major depressive disorder (MDD) is one of the leading causes of disability worldwide. Polymorphisms in cytochrome P450 genes (CYP450) were demonstrated to play a significant role in antidepressant response and side effects, but their effect in real-world clinical practice is poorly known. We determined the metabolic status of CYP2C19 based on the combination of *1, *2, *3 and *17 alleles extracted from genome-wide data in 1239 patients with MDD, pharmacologically treated in a naturalistic setting. Symptom improvement and side effects were assessed using the Montgomery and Åsberg Depression Rating Scale and the Udvalg for Kliniske Undersøgelse scale, respectively. We tested if symptom improvement, response and side effects were associated with CYP2C19 metabolic status adjusting for potential confounders. We considered patients treated with drugs for depression having CYP2C19 genotyping recommended by guidelines (T1 Drugs); secondarily, with all psychotropic drugs having CYP2C19 as relevant metabolic path (T2 Drugs). In the group treated with T1 drugs (n = 540), poor metabolizers (PMs) showed higher response and higher symptom improvement compared to normal metabolizers (p = 0.023 and p = 0.009, respectively), but also higher risk of autonomic and neurological side effects (p = 0.022 and p = 0.022 respectively). In patients treated with T2 drugs (n = 801), similar results were found. No associations between metabolizer status and other types of side effects were found (psychic and other side effects). Our study suggests potential advantages of CYP2C19 pharmacogenetic testing to guide treatment prescription, that may not be limited to the drugs currently recommended by guidelines.
AB - Major depressive disorder (MDD) is one of the leading causes of disability worldwide. Polymorphisms in cytochrome P450 genes (CYP450) were demonstrated to play a significant role in antidepressant response and side effects, but their effect in real-world clinical practice is poorly known. We determined the metabolic status of CYP2C19 based on the combination of *1, *2, *3 and *17 alleles extracted from genome-wide data in 1239 patients with MDD, pharmacologically treated in a naturalistic setting. Symptom improvement and side effects were assessed using the Montgomery and Åsberg Depression Rating Scale and the Udvalg for Kliniske Undersøgelse scale, respectively. We tested if symptom improvement, response and side effects were associated with CYP2C19 metabolic status adjusting for potential confounders. We considered patients treated with drugs for depression having CYP2C19 genotyping recommended by guidelines (T1 Drugs); secondarily, with all psychotropic drugs having CYP2C19 as relevant metabolic path (T2 Drugs). In the group treated with T1 drugs (n = 540), poor metabolizers (PMs) showed higher response and higher symptom improvement compared to normal metabolizers (p = 0.023 and p = 0.009, respectively), but also higher risk of autonomic and neurological side effects (p = 0.022 and p = 0.022 respectively). In patients treated with T2 drugs (n = 801), similar results were found. No associations between metabolizer status and other types of side effects were found (psychic and other side effects). Our study suggests potential advantages of CYP2C19 pharmacogenetic testing to guide treatment prescription, that may not be limited to the drugs currently recommended by guidelines.
KW - Adverse effects
KW - Antidepressive agents
KW - CYP2C19
KW - Cytochrome P450
KW - Metabolism
KW - Pharmacogenetics
KW - Treatment outcome
UR - http://www.scopus.com/inward/record.url?scp=85124424606&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2022.01.008
DO - 10.1016/j.euroneuro.2022.01.008
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C2 - 35152032
AN - SCOPUS:85124424606
VL - 56
SP - 100
EP - 111
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
SN - 0924-977X
ER -
