Clinical effects of lamotrigine combined with duloxetine in the treatment of bipolar depression
- 1Department of Pharmacy, Shenzhen Longhua District Central Hospital, The Affiliated Longhua Hospital of Shenzhen University
- 2Department of Neurology, Shenzhen Longhua District Central Hospital, The Affiliated Longhua Hospital of Shenzhen University
- 3School of Ocean and Tropical Medicine, The Marine Biomedical Research Institute, Guangdong Medical University
Abstract
Objective This study aims to assess the therapeutic efficacy and safety profile of lamotrigine-duloxetine (LTG + DUL) combination therapy in the treatment of bipolar depression (BD), with a focus on understanding cortisol-mediated adverse drug reactions. Methods In this retrospective cohort study, 104 adults with BD initiating lamotrigine (LTG) therapy between January 2023 and December 2024 were stratified into monotherapy (LTG, n=56) and combination therapy (LTG + duloxetine [DUL], n=48) groups through clinician-driven treatment algorithms. A multidimensional assessment protocol was implemented over 16 weeks. Systematically clinical effect and safty were assessed by including Hamilton Depression Rating Scale (HAMD), Montreal Cognitive Assessment (MoCA), neurochemical dynamics serum 5-hydroxytryptamine (5-HT) and cortisol (CS), safety endpoints (LTG - related adverse reactions). Results After 8 weeks of treatment, the group receiving LTG + DUL exhibited significantly greater improvement in depressive symptoms compared to the LTG monotherapy group. At the 12-week mark, the LTG + DUL group demonstrated increased serum 5-HT levels and decreased CS levels relative to the LTG group (P < 0.05). By 16 weeks, the LTG + DUL group achieved higher scores on the MoCA than the LTG group (P < 0.05). Additionally, by the 16-week point, the incidence of lamotrigine-related adverse reactions was significantly higher in the LTG + DUL group compared to the LTG group (P < 0.05), potentially linked to the reduction in serum cortisol levels. Conclusion The combination therapy of LTG + DUL exhibits statistically superior efficacy over LTG monotherapy in treating BD. However, the cortisol-lowering effect of the combination therapy may increase the risk of mild cutaneous adverse reactions associated with LTG. These findings underscore the importance of monitoring cortisol levels in patients undergoing combination therapy, thereby contributing to pharmacovigilance strategies in precision psychiatry. Clinical trial number Not applicable.
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BibTeX
@article{wang2026clinical,
title = {{Clinical effects of lamotrigine combined with duloxetine in the treatment of bipolar depression}},
author = {Xiaokang Wang and Shanshan Li and Yuxian Chen and Gengrui Xu and Lin Jiang and Jiaoyu Rao},
journal = {BMC Pharmacology and Toxicology},
year = {2026},
month = jun,
doi = {10.1186/s40360-026-01164-6},
url = {https://doi.org/10.1186/s40360-026-01164-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - Clinical effects of lamotrigine combined with duloxetine in the treatment of bipolar depression
AU - Xiaokang Wang
AU - Shanshan Li
AU - Yuxian Chen
AU - Gengrui Xu
AU - Lin Jiang
AU - Jiaoyu Rao
PY - 2026
DA - 2026/06/01
JO - BMC Pharmacology and Toxicology
DO - 10.1186/s40360-026-01164-6
UR - https://doi.org/10.1186/s40360-026-01164-6
AB - Objective This study aims to assess the therapeutic efficacy and safety profile of lamotrigine-duloxetine (LTG + DUL) combination therapy in the treatment of bipolar depression (BD), with a focus on understanding cortisol-mediated adverse drug reactions. Methods In this retrospective cohort study, 104 adults with BD initiating lamotrigine (LTG) therapy between January 2023 and December 2024 were stratified into monotherapy (LTG, n=56) and combination therapy (LTG + duloxetine [DUL], n=48) groups through clinician-driven treatment algorithms. A multidimensional assessment protocol was implemented over 16 weeks. Systematically clinical effect and safty were assessed by including Hamilton Depression Rating Scale (HAMD), Montreal Cognitive Assessment (MoCA), neurochemical dynamics serum 5-hydroxytryptamine (5-HT) and cortisol (CS), safety endpoints (LTG - related adverse reactions). Results After 8 weeks of treatment, the group receiving LTG + DUL exhibited significantly greater improvement in depressive symptoms compared to the LTG monotherapy group. At the 12-week mark, the LTG + DUL group demonstrated increased serum 5-HT levels and decreased CS levels relative to the LTG group (P < 0.05). By 16 weeks, the LTG + DUL group achieved higher scores on the MoCA than the LTG group (P < 0.05). Additionally, by the 16-week point, the incidence of lamotrigine-related adverse reactions was significantly higher in the LTG + DUL group compared to the LTG group (P < 0.05), potentially linked to the reduction in serum cortisol levels. Conclusion The combination therapy of LTG + DUL exhibits statistically superior efficacy over LTG monotherapy in treating BD. However, the cortisol-lowering effect of the combination therapy may increase the risk of mild cutaneous adverse reactions associated with LTG. These findings underscore the importance of monitoring cortisol levels in patients undergoing combination therapy, thereby contributing to pharmacovigilance strategies in precision psychiatry. Clinical trial number Not applicable.
SN - 2050-6511
ER -