Mental Health in Cystic Fibrosis in the Modulator Era: Epidemiology, Prognostic Significance, and Therapeutic Implications

Individuals with cystic fibrosis (CF) face significant treatment burdens, and as life expectancy has increased, there is growing emphasis on their psychosocial well-being. Prevalence data indicate that approximately one-quarter to one-third of individuals with CF and their caregivers experience clinically significant anxiety or depression. Specifically, pooled global estimates report an anxiety prevalence of 24.9% (95% CI: 20.8–28.9%) and depression prevalence of 13–33% in adults with CF, with caregivers experiencing even higher rates (anxiety: 35–38%; depression: 20–35%). Depression is independently associated with a nearly twofold increase in mortality risk and substantially higher healthcare costs, underscoring its prognostic significance. These mental health comorbidities are consistently associated with reduced treatment adherence, diminished quality of life, increased healthcare utilisation, and decreased survival. Accordingly, psychological well-being has emerged as a key patient outcome that directly shapes engagement with care and the effectiveness of long-term CF management. International CF guidelines now recommend routine mental health screening within multidisciplinary care frameworks. Evidence-based interventions include cognitive–behavioural therapy (CBT), which is endorsed as a primary treatment, although access remains limited, and stepped-care pharmacotherapy, primarily selective serotonin reuptake inhibitors (SSRIs), for moderate to severe symptoms. Telemedicine and other digital health approaches have expanded access to psychological support, with remote CBT and online programmes demonstrating feasibility and symptom improvement during the COVID-19 pandemic and beyond. The advent of CFTR modulator therapies has significantly altered clinical outcomes, enabling many patients to achieve improved lung function and daily functioning. Nevertheless, mental health challenges persist, as individuals navigate new identity shifts and anxieties despite enhanced physical health. The implementation of mental healthcare remains inconsistent; while screening rates have increased, timely follow-up and integrated psychosocial support are frequently insufficient across care centres. This narrative review highlights the ongoing need to integrate mental health management into CF care to optimise adherence, patient outcomes, and long-term survival in the current therapeutic landscape.