PMID- 37655981
OWN - NLM
STAT- Publisher
LR  - 20231024
IS  - 1531-6971 (Electronic)
IS  - 1070-5287 (Print)
IS  - 1070-5287 (Linking)
VI  - 29
IP  - 6
DP  - 2023 Nov 1
TI  - Neuropsychiatric adverse effects from CFTR modulators deserve a serious research 
      effort.
PG  - 603-609
LID - 10.1097/MCP.0000000000001014 [doi]
AB  - PURPOSE OF REVIEW: This review highlights the problem of neuropsychiatric adverse 
      effects (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI), current 
      suboptimal mitigation approaches, a novel testable mechanistic hypothesis, and 
      potential solutions requiring further research. RECENT FINDINGS: Studies show 
      that a minority of persons with cystic fibrosis (PwCF) initiating cystic fibrosis 
      transmembrane conductance regulator (CFTR) modulators experience neuropsychiatric 
      AEs including worsening mood, cognition, anxiety, sleep, and suicidality. The 
      GABA-A receptor is a ligand-gated chloride channel, and magnetic resonance 
      spectroscopy neuroimaging studies have shown that reduced GABA expression in 
      rostral anterior cingulate cortex is associated with anxiety and depression. 
      Recent research details the impact of peripheral inflammation and the gut-brain 
      axis on central neuroinflammation. Plasma ETI concentrations and sweat chloride 
      have been evaluated in small studies of neuropsychiatric AEs but not validated to 
      guide dose titration or correlated with pharmacogenomic variants or 
      safety/efficacy. SUMMARY: Although ETI is well tolerated by most PwCF, some 
      experience debilitating neuropsychiatric AEs. In some cases, these AEs may be 
      driven by modulation of CFTR and chloride transport within the brain. 
      Understanding biological mechanisms is a critical next step in identifying which 
      PwCF are likely to experience AEs, and in developing evidence-based strategies to 
      mitigate them, while retaining modulator efficacy.
CI  - Copyright (c) 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
FAU - VanElzakker, Michael B
AU  - VanElzakker MB
AD  - Massachusetts General Hospital, Boston.
FAU - Tillman, Emma M
AU  - Tillman EM
AD  - Indiana University School of Medicine, Indianapolis, USA.
FAU - Yonker, Lael M
AU  - Yonker LM
AD  - Massachusetts General Hospital, Boston.
FAU - Ratai, Eva-Maria
AU  - Ratai EM
AD  - Massachusetts General Hospital, Boston.
FAU - Georgiopoulos, Anna M
AU  - Georgiopoulos AM
AD  - Massachusetts General Hospital, Boston.
LA  - eng
GR  - K08 HL143183/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20230901
PL  - United States
TA  - Curr Opin Pulm Med
JT  - Current opinion in pulmonary medicine
JID - 9503765
SB  - IM
PMC - PMC10552811
MID - NIHMS1926775
COIS- MBV reports grants from the National Institutes of Health; and service on the 
      board of directors of PolyBio Research Foundation. EMT reports grants and travel 
      reimbursement from the Cystic Fibrosis Foundation; grants from the National 
      Institutes of Health; and personal fees from Snow Companies. LY reports grants 
      from the Cystic Fibrosis Foundation and grants from the National Heart, Lung, and 
      Blood Institute. EMR reports personal fees from Columbia University for a talk in 
      2022; personal fees from Imaging Endpoints; grants and travel reimbursement from 
      the National Institutes of Health; grants from the National Science Foundation; 
      and service on the advisory board of Brain Spec. AMG reports personal fees from 
      the Belgian Cystic Fibrosis Foundation/King Baudouin Foundation; grants, personal 
      fees, and travel reimbursement from 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; grants from 
      the National Heart, Lung, and Blood Institute; personal fees from Saudi Pediatric 
      Pulmonology Association; grants and personal fees from Vertex Pharmaceuticals; 
      and personal fees from Virginia Commonwealth University.
EDAT- 2023/09/01 12:42
MHDA- 2023/09/01 12:42
PMCR- 2023/10/05
CRDT- 2023/09/01 09:33
PHST- 2023/09/01 12:42 [pubmed]
PHST- 2023/09/01 12:42 [medline]
PHST- 2023/09/01 09:33 [entrez]
PHST- 2023/10/05 00:00 [pmc-release]
AID - 00063198-990000000-00109 [pii]
AID - MCP290610 [pii]
AID - 10.1097/MCP.0000000000001014 [doi]
PST - ppublish
SO  - Curr Opin Pulm Med. 2023 Nov 1;29(6):603-609. doi: 10.1097/MCP.0000000000001014. 
      Epub 2023 Sep 1.