Case Report|Articles in Press

Suicide attempts in adolescents with cystic fibrosis on Elexacaftor/Tezacaftor/Ivacaftor therapy

Published:February 07, 2023DOI:


      • We report 2 adolescents with CF who attempted suicide shortly after starting ETI.
      • Mental adverse effects of CFTR modulators were reported in previous studies.
      • Impact of chronic disease and the COVID-19 pandemic are likely contributing factors.
      • Providers should be vigilant of mental health issues in adolescent with CF on ETI.
      • Mental health screening should be performed regularly after initiation of ETI therapy.


      Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a recently approved cystic fibrosis (CF) transmembrane conductance regulator modulator therapy that has shown promising clinical and laboratory improvements on multiple organ systems in people with CF (pwCF). While original clinical trials found little to no effect on depression and anxiety, many post-marketing reports have suggested that ETI may be associated with adverse mental health effects. Here we report on two pwCF with adverse mental health effects shortly after starting ETI. Although many factors such as the burden of living with a chronic disease or widespread effects of the Covid-19 pandemic may have contributed to these events, similar reports have led to mounting concern that ETI may be the cause of such events. Regular mental health screening before the initiation of ETI and monitoring for signs and symptoms of mental diseases afterward should be a routine part of care, given the gravity of possible outcomes.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Cystic Fibrosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Quittner A.L.
        • et al.
        International committee on mental health in cystic fibrosis: cystic fibrosis foundation and european cystic fibrosis society consensus statements for screening and treating depression and anxiety.
        Thorax. 2016; 71: 26-34
        • Westcott K.A.
        • et al.
        The impact of COVID-19 shielding on the wellbeing, mental health and treatment adherence of adults with cystic fibrosis.
        Future Healthc J. 2021; 8: e47-e49
        • Czeisler M.E.
        • et al.
        Mental health, substance use, and suicidal ideation during the COVID-19 pandemic - United States, June 24-30, 2020.
        MMWR Morb Mortal Wkly Rep. 2020; 69: 1049-1057
        • Smith B.A.
        • et al.
        Impact of COVID-19 on mental health: effects on screening, care delivery, and people with cystic fibrosis.
        J Cyst Fibros. 2021; 20: 31-38
      1. Cystic Fibrosis Foundation Patient Registry 2020 Annual Data Report. 2020 [cited 2022 June 14]; Available from:

      2. FDA. FDA approves new breakthrough therapy for cystic fibrosis. 2019 [cited 2022 June 14]; Available from:

        • Dagenais R.V.E.
        • Su V.C.H.
        • Quon B.S.
        Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: a Systematic Review.
        J Clin Med. 2020; 10
        • Johnson J.G.
        • et al.
        The patient health questionnaire for adolescents: validation of an instrument for the assessment of mental disorders among adolescent primary care patients.
        J Adolesc Health. 2002; 30: 196-204
        • Guo Y.
        • et al.
        Expression and distribution of cystic fibrosis transmembrane conductance regulator in neurons of the human brain.
        J Histochem Cytochem. 2009; 57: 1113-1120
        • Spoletini G.
        • et al.
        Dose adjustments of Elexacaftor/Tezacaftor/Ivacaftor in response to mental health side effects in adults with cystic fibrosis.
        J Cyst Fibros. 2022;
        • Moussavi S.
        • et al.
        Depression, chronic diseases, and decrements in health: results from the World Health Surveys.
        Lancet. 2007; 370: 851-858
        • Quittner A.L.
        • et al.
        Prevalence and impact of depression in cystic fibrosis.
        Curr Opin Pulm Med. 2008; 14: 582-588
        • Riekert K.A.
        • et al.
        The association between depression, lung function, and health-related quality of life among adults with cystic fibrosis.
        Chest. 2007; 132: 231-237
        • Smith B.A.
        • Wood B.L.
        Psychological factors affecting disease activity in children and adolescents with cystic fibrosis: medical adherence as a mediator.
        Curr Opin Pediatr. 2007; 19: 553-558
        • Snell C.
        • et al.
        Depression, illness severity, and healthcare utilization in cystic fibrosis.
        Pediatr Pulmonol. 2014; 49: 1177-1181
      3. Cystic Fibrosis Foundation Patient Registry 2019 Annual Data Report. 2019 [cited 2022 June 14]; Available from:

        • Lantos J.D.
        • et al.
        Suicide Risk in Adolescents During the COVID-19 Pandemic.
        Pediatrics. 2022; 149
      4. Organization, W.H. Mental Health and COVID-19: early evidence of the pandemic's impact: scientific brief. 2022 [cited 2022 June 14]; Available from:

      5. Brunier, A. COVID-19 pandemic triggers 25% increase in prevalence of anxiety and depression worldwide: wake-up call to all countries to step up mental health services and support, in World Health Organization News. 2022 [cited 2022 November 21]; Available from:

        • Panchal U.
        • et al.
        The impact of COVID-19 lockdown on child and adolescent mental health: systematic review.
        Eur Child Adolesc Psychiatry. 2021;
        • Sutharsan S.
        • et al.
        Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial.
        Lancet Respir Med. 2022; 10: 267-277
        • Heo S.
        • et al.
        Mental status changes during elexacaftor/tezacaftor /ivacaftor therapy.
        J Cyst Fibros. 2022; 21: 339-343
        • Lyman B.C.
        • et al.
        Elexacaftor-tezacaftor-ivacaftor overdose in an adolescent female with cystic fibrosis.
        Pediatr Pulmonol. 2022; 57: 3174-3176
        • Barry P.J.
        • et al.
        Triple therapy for cystic fibrosis Phe508del-gating and -residual function genotypes.
        N Engl J Med. 2021; 385: 815-825
        • Page A.
        • Goldenberg A.
        • Matthews A.L.
        Lived experiences of individuals with cystic fibrosis on CFTR-modulators.
        BMC Pulm Med. 2022; 22: 42
        • Vance T.
        • et al.
        Mental health implications of genetic modulator therapy in CF: depression and anxiety screening for pediatric patients prescribed elexacaftor/tezacaftor/ivactor during the COVID-19 pandemic.
        J Cyst Fibros. 2021; : S142-S143