Neuropsychiatric adverse effects following switch to vanzacaftor–tezacaftor–deutivacaftor in adults with cystic fibrosis: early experience from a regional centre

Vanzacaftor-tezacaftor-deutivacaftor (VTD) is the newest triple-combination CFTR modulator, licensed as an alternative to elexacaftor-tezacaftor-ivacaftor (ETI). Neuropsychiatric adverse effects are recognised with ETI and now carry a specific post-marketing warning for VTD. At our regional adult cystic fibrosis centre (454 patients under follow-up), 87 have been commenced on VTD, mainly for elevated sweat chloride on ETI and dosing preference. Three individuals with pre-existing mental health conditions were proactively started on a reduced dose (one tablet daily); two of three showed sweat chloride improvement below 40 mmol/L, with no reported adverse effects. Among the remaining patients, four (4.6%) developed new-onset or worsening psychiatric symptoms at standard dose. Three had no prior psychiatric history; one had pre-existing depression on long-term sertraline that markedly worsened. Onset ranged from two weeks to four months. Three of four showed a good physiological response, with further sweat chloride reduction and stable or improved lung function; the fourth switched back too rapidly for retesting. Three patients required switching back to ETI, with resolution of symptoms within days; one continued VTD with resolution by three months. This rate is comparable to previously reported real-world ETI rates (7% and 7.9%), though more of our cases involved suicidal ideation and required full discontinuation. Cases were identified clinically rather than through systematic screening, which may affect detection rates. These findings highlight the need for early mental health screening after VTD initiation and a low threshold for psychiatric review. All cases have been reported to the MHRA Yellow Card scheme.