ArticleBMC pharmacology & toxicology2026
Clinical effects of lamotrigine combined with duloxetine in the treatment of bipolar depression.
Article in BMC pharmacology & toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveThis 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.
methodsIn 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).
resultsAfter 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.
conclusionThe 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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