Background: Limited existing research on mental health and health-related quality of life (HRQoL) in people with hemophilia (PwH) suggests these patients still may have poor mental health despite treatment advances significantly improving somatic outcomes.

Objectives: This multicenter study aimed to systematically assess mental health and HRQoL and their association with disease severity, age and treatment regimen among PwH.

Methods: This cross-sectional study, conducted in nine Swiss hemophilia treatment centers, included participants aged six years and older with congenital hemophilia of any severity. The study procedure comprised a semi-structured psychiatric diagnostic interview and an online survey comprising age-validated psychological measures to capture mental health and HRQoL. Treatment centers provided clinical data.

Results: Of 164 PwH enrolled in the study, 156 participants completed the psychiatric diagnostic interview. 25% met the criteria for a mental disorder (MD). Most common among the MD were affective disorders, substance use disorders, and attention deficit hyperactive disorder. Moderate/severe hemophilia and lower baseline factor activity were significantly associated with higher psychopathology and lower HRQoL. Of participants with moderate/severe hemophilia, 26% of those on prophylaxis versus 45% of those on on-demand met the criteria for an MD.

Conclusions: Elevated prevalence of MD, and the association of psychopathology with disease severity and treatment regimen, highlights the continued relevance of mental health in hemophilia research. Further objective clinical research is indispensable to define targets for improved and individualized comprehensive treatment care plans.

Plain language summary: Major treatment advances have transformed hemophilia care, allowing most people with hemophilia (PwH) to have average lifespans. Reduced bleeding complications have shifted attention to overall well-being and mental health of PwH. The multicenter Swiss HERMES study examined 164 children and adults with hemophilia to explore the link between disease severity, treatment regimen, mental health, and health-related quality of life using standard questionnaires and a psychiatric interview. About one in four participants had at least one mental disorder-most often depression, substance use disorders, or ADHD. Participants with moderate or severe hemophilia, or lower clotting factor levels, reported poorer health-related quality of life. Prophylactic treatment may support mental health in participants with moderate or severe hemophilia. These findings show that mental health issues are common in PwH and highlight the need to integrate psychological screening and support into comprehensive hemophilia care.