Mental Health of Pediatric Patients with Cystic Fibrosis after 18 Months on Elexacaftor-Tezacaftor-Ivacaftor Therapy

Background: Research studies are conflicting regarding new highly effective modulators and the association with mental health symptoms for adults and adolescents with cystic fibrosis (CF). For younger children, small studies and case reports indicate a wide range of effects, ranging from improvement in mood to the development of neuropsychiatric symptoms. However, a large placebo-controlled study indicated no causal connection. This study evaluates the frequency and severity of mental health symptoms in children and adolescents while taking elexacaftor/tezacaftor/ivacaftor (ETI).

Methods: The study includes 81 pediatric patients with CF followed at Nationwide Children's Hospital (NCH). Patient Reported Outcomes Measurement Information System (PROMIS)-Anxiety and Depression, Patient Health Questionnaire 8 (PHQ-8) and Generalized Anxiety Disorder Questionnaire (GAD-7) were used to screen for depression and anxiety. Age-appropriate questionnaires were completed over the first 18 months after initiating ETI.

Results: At baseline, majority of participants reported mental health symptoms within normal limits (WNL). For participants with elevated baseline measures, depressive and anxiety symptoms significantly decreased throughout the study period. Depending on the metric, patients experiencing depressive and anxiety symptoms dropped to 2-3% (n = 1, on each depressive measure) and 0% (n = 0, on either anxiety measures) respectively by 18 months.

Conclusion: Most pediatric patients with CF did not endorse symptoms of depression or anxiety disorders at ETI initiation. Over the first 18 months of ETI usage, the percentage of patients with these symptoms decreased, suggesting that the percentage of patients experiencing severe symptoms of depression and anxiety may decrease with ongoing use of ETI.