Background/Purpose: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease predominantly affecting woman of child-bearing age. Concurrent fibromyalgia syndrome (FMS) has been reported in up to 40% of patients with SLE, which markedly affects their daily functionality and life satisfaction. Anti-depressants are used for the pharmacological therapy of FMS in both the general population and patients with connective tissue diseases. These agents include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) and atypical antidepressants. Hydroxychloroquine (HCQ) is widely used in patients with SLE due to its immunomodulatory action on reducing lupus disease activity and good overall tolerance and safety profiles. However, both antidepressants and HCQ are reported to cause QT interval prolongation, a cardiac measure that serves as a surrogate indicator for increased risk of torsade de pointes, a potential lethal ventricular arrhythmia that can result in sudden death. A recent study of hospitalized COVID-19 patients being treated with combination HCQ and azithromycin observed prolonged QT intervals and events of torsade de pointes, raising concern of additive risk for arrhythmic mortality when HCQ is used concomitantly with other QT-prolonging medications including antidepressants. Our objective is to investigate the risk of QT prolongation associated with hydroxychloroquine use with and without concurrent use of antidepressants in SLE patients with fibromyalgia.

Methods: This is a retrospective analysis using electronic medical records sampling SLE patients who participated in Yale Lupus Wellness Program from 2016 to 2019. All patients included met 2012 SLICC classification criteria for SLE. 97 patients in the program had 12-lead ECG with QTc interval measures. 52 patients used HCQ alone, while 45 patients concomitantly used both HCQ and antidepressants including SSRI, SNRI, TCA, or tramadol. QTc intervals were compared in groups taking HCQ alone versus those taking HCQ and antidepressants.

Results: The average QTc interval was found to be 430 milliseconds at baseline, which was increased to 441 milliseconds after HCQ usage for 3 months or greater (p < 0.05). The average QTc interval was 436 milliseconds in total HCQ dose less than 720 g versus 447 milliseconds in total HCQ dose greater than 720 g (p > 0.05). However, QTc interval was found to be similar with and without concurrent use of antidepressants (451 milliseconds in patient on HCQ alone vs. 447 milliseconds in patients on HCQ with antidepressants) in this cohort study.

Conclusion: Our study indicates that chronic use of HCQ is associated with QTc interval prolongation in patients with SLE. However, concurrent use antidepressants for fibromyalgia did not appear to further increase QTc interval.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluating-the-risk-of-qt-prolongation-associated-with-hydroxychloroquine-use-with-and-without-antidepressants-in-sle-patients-with-fibromyalgia/