Psychoactive medication use and cardiac electrophysiology in hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder: a retrospective analysis

Context Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorder (HSD) are connective tissue disorders associated with musculoskeletal manifestations and significant psychiatric comorbidities. Psychoactive medications commonly utilized in these populations raise concerns regarding potential cardiac effects. Objectives This study explores associations between psychoactive medication utilization and electrocardiogram (ECG) parameters in patients with hypermobile Ehlers-Danlos syndrome (hEDS) and HSD to provide insight into potential cardiac considerations in this population. Methods This retrospective analysis included de-identified data from patients referred for cardiac evaluation at the Long Island Heart Rhythm Center between January 2019 and June 2023. Diagnosis of EDS and HSD were made utilizing the 2017 International Classification criteria. Psychiatric diagnoses were classified per DSM-5 criteria, and psychoactive medications were categorized utilizing NIH guidelines. ECG parameters, psychiatric diagnoses, and psychoactive medication use were compared between groups. Statistical analyses included Student’s t-tests for continuous variables, chi-square or Fisher’s exact tests for categorical variables, and odds ratio (OR) calculations. Results Among 109 patients (hEDS: n=75; HSD: n=34), psychiatric diagnoses were more prevalent in hEDS patients (72 vs. 38.2 %; p=0.008), with significant differences in trauma- and stressor-related disorders (p=0.009) and ADHD (p=0.006). hEDS patients had a higher mean psychoactive medication use (1.8 vs. 1.1; p=0.019) and greater anticonvulsant use (33.3 vs. 8.8 %; p=0.008). In a subset with ECG data (n=62), QTc intervals were significantly shorter in hEDS patients (421.62 ± 22.47 ms vs. 436.73 ± 18.74 ms; p=0.022), yet within normal ranges. QTc prolongation was more frequent in HSD patients (26.7 vs. 6.4 %; OR 5.33; 95 % confidence interval (CI) [1.04–27.39]; p=0.045). Conclusions hEDS patients had a higher psychiatric burden and psychoactive medication use than HSD patients, but ECG parameters largely remained within normal limits. The increased QTc prolongation in HSD patients highlights potential cardiovascular risks, requiring further investigation. Routine cardiovascular monitoring and interdisciplinary care are recommended for hypermobile patients on psychoactive medications.