Depression, Immunosuppressant Levels, and Clinical Outcomes in Postlung Transplant Recipients

Abstract

Objective Posttransplant depression has been linked to increased risk for adverse outcomes in lung transplant patients. Maintaining target serum immunosuppressant levels is also essential for optimal lung transplant clinical outcome and may be a crucial predictor of outcomes. Because depression could affect medication nonadherence, resulting in out-of-range immunosuppressant levels, we examined the relationship between posttransplant depression, immunosuppressant medication trough level variability, indexed by out-of-range values on clinical outcomes and coefficient of variability, and clinical outcomes. Method A consecutive series of 236 lung transplant recipients completed the Center for Epidemiological Studies-Depression two-month posttransplant. Immunosuppressant trough levels (i.e., tacrolimus or cyclosporine) within the range of individualized immunosuppressant targets were obtained at three-, six-, nine-month follow-up clinic visits. Clinical outcomes including hospitalizations and mortality were obtained from medical records. Results Fourteen percent of patients were classified as depressed (Center for Epidemiological Studies-Depression ≥16), 144 (61%) of patients had at least 25% out-of-range immunosuppressant values, and the average coefficient of variability was 36%. Over a median of 2.6 years (interquartile range = 1.2), 32 participants died (14%) and 144 (61%) had at least one unplanned, transplant-related hospitalization. Both depression (hazard ratio = 1.45 (1.19, 1.76), p < . 01) and immunosuppressant variation (immunosuppressant out-of-range: hazard ratio = 1.41 (1.10, 1.81), p < .01) independently predicted more frequent hospitalizations and higher mortality. Conclusions Early posttransplant depression was associated with significantly worse clinical outcomes. While immunosuppressant level variability is also related to adverse outcomes, such variability does not account for increased risk observed with depression.