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Introduction In recent years, burn centers are managing more patients with exfoliative skin disorders including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and SJS/TEN overlap. While it is well known that burn patients have higher rates of co-morbid psychiatric disorders than the general population, the incidence of pre-existing psychiatric disorders among patients who develop SJS, SJS/TEN overlap, and TEN is unknown. This study aimed to characterize a cohort of patients with pre-existing psychiatric disorders admitted to a tertiary burn center for treatment of SJS, SJS/TEN overlap, and TEN with specific focus on those who received the offending agent for a psychiatric indication. Methods A retrospective descriptive case series using an institutional burn center registry was performed. All patients admitted to a single verified burn center between January 1, 2009 and December 31, 2018 with biopsy-proven SJS, SJS/TEN overlap, or TEN and the presence of a co-morbid psychiatric disorder were identified. Demographic, hospital, and clinical information were extracted from the burn registry and verified through review of the electronic medical record. Results Among 168 patients with biopsy-proven SJS, SJS/TEN overlap, or TEN, 18% (30/168) had a pre-existing psychiatric disorder, with the offending agent being prescribed for a psychiatric indication in 30% (10/30) of patients. Lamotrigine was the offending agent in 80% of cases and prescribed 100% of the time for a psychiatric indication. Of those who received lamotrigine, patients were 100% female, 63% black, and had an average age of 38 years. The mean length of stay was 24 days and 88% received a psychiatric consultation. While 75% of patients were started on lamotrigine for a diagnosis of bipolar disorder, none of these patients met criteria for bipolar disorder. Conclusions Pre-existing psychiatric comorbidity is less common among patients that develop SJS, SJS/TEN overlap, and TEN than in burn-injured patients. For patients with pre-existing psychiatric disorders who develop these potentially fatal skin diseases from an offending agent that was prescribed for a psychiatric indication, early involvement of psychiatry colleagues is recommended to ensure proper psychiatric diagnosis and management moving forward. Applicability of Research to Practice This study highlights the importance of accurate assessment for and diagnosis of bipolar disorder prior to determining treatment approach. For the burn surgeon treating these patients, early involvement of psychiatric consultants is recommended and extremely important.