Insomnia and Relationship with Immunosuppressant Therapy After Lung Transplantation

Purpose:   Lung transplant recipients are at high risk of developing sleep disorders such as sleep apnea and restless legs syndrome.  Anecdotal evidence indicates that insomnia is also common in lung transplant recipients, yet its prevalence and features are poorly characterized.  We sought to evaluate the prevalence of insomnia and the relationship with immunosuppressant medications following lung transplantation.

Methods:  To date we have enrolled 34 subjects who did not have sleep problems prior to transplant and who had undergone lung transplantation at least six weeks prior to study entry.  Insomnia was assessed using the Insomnia Severity Index (ISI), and using separate questions about frequency of difficulty initiating and maintaining sleep, awakenings, and subjective sleep latency.  Exposure to tacrolimus for each subject was assessed by plotting days since transplant on the x-axis and every tacrolimus serum concentration after transplant on the y-axis and calculating area-under-the-curve (AUC).

Results:   To date, 22 out of 34 subjects report subclinical insomnia or clinical insomnia using the ISI (65%).  Mean±SEM tacrolimus AUC was higher in patients reporting subthreshold or clinical insomnia (11422±2095 ng·days/mL) compared to those not reporting insomnia (7586±2601 ng·days/mL).  Tacrolimus AUC increased in a stepwise-manner with reported frequency of difficulty initiating sleep.  AUC was 7637±1840 ng·days/mL (never or rarely had difficulty initiating sleep), 8904±3599 ng·days/mL (sometimes had difficulty initiating sleep), and 14544±3119 ng·days/mL (often or almost always had difficulty initiating sleep).  Subject enrollment is ongoing and statistical analyses will be performed on the subsequent larger sample size.

Conclusions:   In our cohort, insomnia is common after lung transplantation, with prevalence greater than in the general population.  Insomnia complaint is associated with greater exposure to tacrolimus.  Future research should investigate the relationship between immunosuppressant therapy and development of sleep disorders.