Risk of psychiatric disorders in patients who underwent solid organ transplantation and the role of immunosuppressants: real-world evidence

Psychiatric disorders are increasingly recognized as important complications following solid organ transplantation, yet large-scale longitudinal evidence remains limited. This study aimed to evaluate the association between solid organ transplantation, immunosuppressant use, and the risk of psychiatric disorders. This longitudinal, population-based retrospective study used data from Taiwan’s National Health Insurance Research Database from 2002 to 2022. Adults who underwent solid organ transplantation between 2003 and 2019 were identified as the transplant cohort, while individuals without a history of organ transplantation served as controls. Patients who received more than one type of organ transplant, had pre-existing psychiatric disorders, or had missing data were excluded. Propensity score matching was performed at a 1:5 ratio to balance age, sex, socioeconomic status, index year, and Charlson Comorbidity Index between transplant recipients and controls. The primary outcome was incident psychiatric disorders, defined using ICD-9-CM and ICD-10-CM diagnostic codes. Cox proportional hazards models were used to estimate hazard ratios for psychiatric disorders associated with solid organ transplantation, and Kaplan–Meier analysis was performed to assess cumulative incidence. In addition, a separate case–control analysis within the transplant cohort was conducted to evaluate the association between immunosuppressant use and psychiatric disorders. Patients with psychiatric disorders were matched to those without psychiatric disorders at a 1:4 ratio, and exposure to immunosuppressive agents within 1 year before the index date was assessed. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between individual immunosuppressants and psychiatric disorders. Among 9356 transplant recipients and 46,780 matched controls, solid organ transplantation was associated with an increased risk of psychiatric disorders (adjusted HR 1.11, 95% CI 1.04–1.19). Liver transplantation showed a significant association (HR 1.21, 95% CI 1.09–1.34), while kidney and lung transplantation were not significantly associated. In the case–control analysis, cyclosporine (OR 1.29, 95% CI 1.06–1.57), tacrolimus (OR 1.35, 95% CI 1.14–1.59), and azathioprine (OR 1.59, 95% CI 1.03–2.45) were associated with increased risk in solid organ transplantation patients. Solid organ transplantation was associated with a modest increase in psychiatric disorder risk, with variation across transplant types and immunosuppressive regimens. These findings underscore the importance of psychiatric monitoring in this population, although causal interpretation should be made cautiously.