Clinical effects of lamotrigine combined with duloxetine in the treatment of bipolar depression

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2026年6月10日

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Xiaokang Wang,
Shanshan Li,
Yuxian Chen,
Gengrui Xu,
Lin Jiang,
Jiaoyu Rao

摘要

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.