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Interaction effect of serum serotonin level and age on the 12-week pharmacotherapeutic response in patients with depressive disorders

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Wonsuk Choi, Ju Wan Kim, Hee Ju Kang, Hee Kyung Kim, Ho Cheol Kang, Ju Yeon Lee, Sung Wan Kim, Robert Stewart, Jae Min Kim

Original languageEnglish
Article number24226
JournalScientific Reports
Issue number1
Early online date20 Dec 2021
Accepted/In press3 Dec 2021
E-pub ahead of print20 Dec 2021
PublishedDec 2021

Bibliographical note

Funding Information: The study was funded by a grant of National Research Foundation of Korea Grant [NRF-2019M3C7A1031345, NRF-2020R1A2C2003472] to J.-M.K. R.S. is part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. R.S. is also a National Institute for Health Research (NIHR) Senior Investigator. Publisher Copyright: © 2021, The Author(s).

King's Authors


Despite the recognized antidepressant role of serotonin (5-hydroxytryptamine [5-HT]) signaling pathways in the central nervous system, the association between baseline peripheral 5-HT level and the antidepressant treatment response in clinical studies remains debatable. We investigated the interaction effects of baseline serum 5-HT level and age on the 12-week remission in outpatients with depressive disorders who received stepwise antidepressant treatment. Baseline serum serotonin levels were measured and the age of 1094 patients recorded. The patients received initial antidepressant monotherapy; then, patients with an insufficient response or who experienced uncomfortable side effects received alternative treatments every 3 weeks (3, 6, and 9 weeks). Subsequently, 12-week remission, defined as a Hamilton Depression Rating Scale (HAMD) score of ≤ 7, was evaluated. Individual and interaction effects of serum 5-HT level (as a binary [low vs. high, based on the median value of 72.6 ng/mL] or continuous variable) and age (as a binary [< 60 vs. ≥ 60 years] or continuous variable) on the 12-week remission rate were analyzed using logistic regression models after adjusting for relevant covariates. High 5-HT (≥ 72.6 ng/mL) and age ≥ 60 years were associated with the highest 12-week remission rates and a significant multiplicative interaction effect. The interaction effect of the two variables on the 12-week remission rate was significant even when analyzed as a continuous variable. Our study suggests that the association between baseline serum 5-HT level and 12-week antidepressant treatment outcomes differs according to patient age.

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