Early Clinical Improvement With Lamotrigine Augmentation in Severe Treatment-Resistant Unipolar Depression: A Case...

Treatment-resistant depression (TRD) is a major clinical challenge, with limited augmentation strategies beyond conventional antidepressants. Lamotrigine, an anticonvulsant licensed for bipolar depression, has been trialled in unipolar TRD, though evidence remains inconsistent, and its use is currently off-license. We describe a 45-year-old gentleman with severe TRD who failed multiple trials of antidepressants, including citalopram and mirtazapine in the community, and subsequently fluoxetine during admission following a suicide attempt. Given his lack of response, lamotrigine augmentation was initiated. Within three weeks, he demonstrated substantial improvement in mood, engagement, and self-care, alongside near-complete resolution of suicidal ideation. Depression severity, measured by the Patient Health Questionnaire-9 (PHQ-9), decreased from 23/27 (severe) to 3/27 (minimal) three weeks post lamotrigine. This rapid response occurred earlier than typically reported in clinical studies. The case highlights lamotrigine as a potentially valuable augmentation option in TRD and emphasises the need for further research to clarify its efficacy and predictors of early response.