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.