(137) Vortioxetine: A Safe Treatment for Depression in a Medically Complex Patient with QTc Prolongation

Background/Significance: Depression is a common psychiatric illness, particularly in medically ill patients (Friedrich, 2017). Serotonergic agents are generally the first-line treatments; however, pharmacologic agent selection requires extra care in patients with medical comorbidities due to drug-drug interactions and greater risk for adverse events (Friedrich, 2017). One side effect of most antidepressants is prolongation of the corrected QT (QTc) interval, which places patients at increased risk for Torsades de pointes and sudden cardiac death when the QTc is greater than 500 milliseconds (ms) (Cuomo, 2022).

Case: We describe a case of a 30-year-old woman with a medical history of hypertension, type 2 diabetes mellitus, and chronic kidney disease grade 4, who was admitted to the medicine service with flash pulmonary edema, hypertensive emergency, and new-onset heart failure, with course complicated by a cerebral vascular accident. Psychiatry was consulted for depressive symptoms; on initial assessment, her score on the Montgomery–Åsberg Depression Rating Scale (MADRS) was 21, consistent with moderate depression (Muller, 2003). On baseline electrocardiogram (ECG), QTc was 473ms. Sertraline 25mg daily was started for depressive symptoms. After two doses, repeat ECG showed QTc prolongation to 522ms; sertraline was discontinued. Given concern for confounders of QTc prolongation, a second trial of sertraline was conducted, again with QTc prolongation (to 533ms). Based on limited available cardiac safety data in healthy, mostly white, young men (Wang, 2013), psychiatry and the electrophysiologist agreed to trial vortioxetine 5mg daily, with close monitoring of QTc via daily ECGs and telemetry monitoring. Her QTc decreased to 481ms and consistently remained below 500ms. After two weeks of treatment, she experienced significant improvement in depressive symptoms; her MADRS score decreased to 4, indicating remission.

Discussion: This case demonstrates the potential cardiac safety and clinical efficacy of vortioxetine in depression for a medically complex patient who, while relatively young, had medical comorbidities more consistent with those of a geriatric patient. Despite QTc prolongation with low-dose sertraline, our patient tolerated a therapeutic dose of vortioxetine with no prolongation of QTc and clinically significant improvement.

Conclusion/Implications: Overall, our case supports the limited data suggesting cardiac safety of vortioxetine, even extending to medically complex patients. It further emphasizes the importance of robust research for this medication in medically complex patients of all ages and diverse backgrounds.

References:
1. Friedrich MJ. Depression is the leading cause of disability around the world. JAMA. 2017 Apr 18;317(15):1517.
2. Cuomo A, Libri C, Barillà G, Cattolico M, Carmellini P, Fagiolini A. QTc interval diurnal variations in patients treated with psychotropic medications: implications for the evaluation of drug induced QTc changes. International Review of Psychiatry. 2022 Nov 17;34(7–8):689–92.
3. Müller M. Differentiating moderate and severe depression using the Montgomery–Åsberg depression rating scale (Madrs). Journal of Affective Disorders. 2003 Dec;77(3):255–60.
4. Wang Y, Nomikos GG, Karim A, Munsaka M, Serenko M, Liosatos M, et al. Effect of vortioxetine on cardiac repolarization in healthy adult male subjects: results of a thorough qt/qtc study: clinical pharmacology in drug development. CPDD. 2013 Oct;2(4):298–309.