Elexacaftor/tezacaftor/ivacaftor and mental health: A workshop report from the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health working group

C J Bathgate; D A Fedele; E M Tillman; J He; R S Everhart; L R Reznikov; F F Liu; K Kirby; K Raffensperger; K Traver; K A Riekert; S W Powers; A M Georgiopoulos

doi:10.1016/j.jcf.2024.11.006

Elexacaftor/tezacaftor/ivacaftor and mental health: A workshop report from the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health working group

J Cyst Fibros. 2024 Nov 26:S1569-1993(24)01814-9. doi: 10.1016/j.jcf.2024.11.006. Online ahead of print.

Authors

C J Bathgate¹, D A Fedele², E M Tillman³, J He⁴, R S Everhart⁵, L R Reznikov⁶, F F Liu⁷, K Kirby⁸, K Raffensperger⁹, K Traver¹⁰, K A Riekert¹¹, S W Powers¹², A M Georgiopoulos¹³

Affiliations

¹ Department of Medicine, National Jewish Health, Denver, CO, USA.
² Center for Healthcare Delivery Science, Nemours Children's Health, Jacksonville, FL, USA.
³ Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS, USA.
⁵ Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
⁶ Department of Physiological Sciences, University of Florida, Gainesville, FL, USA.
⁷ Seattle Children's Cystic Fibrosis Center; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA.
⁸ Community Partner, St. Louis, MO, USA.
⁹ Community Partner, Hoboken, NJ, USA.
¹⁰ Community Partner, Cincinnati, OH, USA.
¹¹ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹² Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital, Cincinnati, OH, USA.
¹³ Department of Child and Adolescent Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address: Ageorgiopoulos@mgh.harvard.edu.

PMID: 39592379
DOI: 10.1016/j.jcf.2024.11.006

Abstract

Background: This report summarizes the 2023 inaugural annual meeting of the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health (PRIME) working group. This workshop focused on mental health and elexacaftor/tezacaftor/ivacaftor (ETI).

Methods: We reviewed existing literature and identified key gaps and study design considerations in preclinical work, pharmacokinetics/pharmacodynamics, mood/anxiety, quality of life/self-perception, neuropsychological symptoms, sleep, and symptom management.

Results: Limited studies have identified behavioral changes with modulator exposure in rodent models of depression, anxiety, and cognition. Longitudinal human studies reporting mean changes generally show no change or improvement. However, case reports and single-center studies identify subgroups reporting new or worsening symptoms.

Conclusions: Future studies should focus on understanding the role of CFTR in the nervous system, defining ETI impacts in preclinical models, and mechanistic investigations. Innovative methods with larger samples and comprehensive assessments are needed to determine the incidence of new/worsening symptoms throughout the lifespan and effective management strategies.

Keywords: Adverse events; Anxiety; CFTR modulators; Cognitive; Mood; Neuropsychological.

Publication types

Review