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

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.
Competing Interests: Declaration of competing interest Bathgate (CJB) reports grants, travel support, and honorarium fees from the Cystic Fibrosis Foundation; and personal fees from Vertex Pharmaceuticals. Everhart (RSE) reports grants, travel support, and honorarium fees from the Cystic Fibrosis Foundation; grant funding from the National Heart, Lung, and Blood Institute. Fedele (DAF) reports grants, travel support, and honorarium fees from the Cystic Fibrosis Foundation; grant funding from the National Heart, Lung and Blood Institute. Georgiopoulos (AMG) reports personal fees from the Belgian Cystic Fibrosis Foundation/King Baudouin Foundation; grants, personal fees and travel reimbursement from the Cystic Fibrosis Foundation, grants from the Dutch Cystic Fibrosis Foundation; travel reimbursement from the European Cystic Fibrosis Society; travel reimbursement from the French Cystic Fibrosis Society; personal fees from the Italian Cystic Fibrosis Research Foundation; grant funding from the National Heart, Lung and Blood Institute, grants and personal fees from Vertex Pharmaceuticals; and personal fees from Virginia Commonwealth University. He (JH) reports grants and honorarium fees from the Cystic Fibrosis Foundation; grant funding from the National Institute of Health (NIH). Kirby (KK) reports honoraria from the Cystic Fibrosis Foundation. Liu (FFL) reports grant funding, travel support, and honorarium fees from the Cystic Fibrosis Foundation; grant funding from the National Institute of Mental Health (NIMH). Powers (SWP) reports grants to his institution from the National Institutes of Health (NINDS, NCCIH, NIDDK, NINR, NCATS), the Patient Centered Outcomes Research Institute, and the Cystic Fibrosis Foundation; travel reimbursement and honoraria from the Cystic Fibrosis Foundation. Reznikov (LRR) reports grants, travel support, and honorarium fees from the Cystic Fibrosis Foundation; grant funding from the National Heart, Lung, and Blood Institute; honoraria and travel support for committee leadership role from NIH, committee leadership role in American Physiological Society. Raffensperger (KR) reports honoraria from the Cystic Fibrosis Foundation. Riekert (KAR) reports grants, travel support, and honorarium fees from the Cystic Fibrosis Foundation and grant funding from the National Institutes of Health (NHLBI, NIDDK). Tillman (EMT) reports grant support and travel reimbursement from the Cystic Fibrosis Foundation. Traver (KLT) reports travel reimbursement and honoraria from the Cystic Fibrosis Foundation, Cystic Fibrosis Learning Network (CFLN) and Cincinnati Children's Medical Center (CCHMC).
(Copyright © 2024. Published by Elsevier B.V.)