Association of Janus kinase inhibitors with reduced depression in alopecia areata

Abstract Background Alopecia areata (AA) is associated with a significant psychological burden, particularly an increased risk of major depressive disorder (MDD). Janus kinase (JAK) inhibitors are emerging as an effective treatment for AA, yet their impact on MDD risk remains unclear. Understanding this association could inform treatment decisions and improve patient outcomes. Objectives This study aimed to determine if treatment with JAK inhibitors is associated with a reduced incidence of MDD in AA patients compared to those receiving other treatments or no treatment. Methods This study utilized the TriNetX international healthcare database, including patients diagnosed with AA between 1 January 2011 and 30 June 2024. Patients were categorized into two groups based on JAK inhibitor use within 6 months after AA diagnosis. Propensity score matching ensured balanced groups across observed covariates. The primary outcome was MDD diagnosis between 6 months and 5 years after AA diagnosis. Secondary outcomes included new antidepressant prescriptions. Results After matching, 1838 patients in each group (conventional treatments with or without JAK inhibitors) were analysed. Treatment with JAK inhibitors was significantly associated with a lower risk of MDD [aHR: 0.42, 95% confidence interval (CI): 0.22–0.82, p = 0.009] and antidepressant prescriptions (aHR: 0.46, 95% CI: 0.32–0.67, p < 0.001). These findings were consistent across 1‐year, 3‐year, 5‐year and 10‐year periods. Subgroup analyses revealed stronger associations in younger patients (18–29 years), those of White ethnicity, and those treated at academic medical centres. Conclusions This study shows that JAK inhibitor treatment in AA patients is associated with a significantly lower incidence of MDD and reduced antidepressant use. These findings suggest a potential role for JAK inhibitor in improving mental health in AA. Randomized controlled trials are warranted to confirm these findings and explore the long‐term safety and benefits of JAK inhibitors.