Abstract

A Cardiovascular side effect, such as arrhythmias and sudden cardiac death (SCD), is associated with tricyclic antidepressants (TCA), which are largely used in the treatment of depression and chronic pain. Their proarrhythmic potential is of concern because of their sodium and potassium channel-blocking effects. Nonetheless, the evidence is not coherent in all the studies with low yields that depend upon dose, duration, comorbidities, and test populations. This systematic review aimed to examine the relationship between the use of TCA and the risk of developing SCD that summarizing the current evidence about cardiovascular effects in patients using such drugs. Original peer-reviewed studies in PubMed, Scopus, and Web of Science within the period 2019 to 2025 were searched in a systematic way. Eligible studies were observational cohort, case-control, or population-based studies that evaluate the exposure to TCA and subsequent SCD or cardiovascular death. Meta-analyses and systematic reviews were not included. The study design, population, TCA exposure, the outcomes, and the ratio of hazards were extracted and synthesized. Eight eligible studies, which included over 650,000 participants, were reviewed. The results revealed that TCAs such as amitriptyline, nortriptyline, and desipramine are most strongly linked to sudden cardiac death (SCD), while lofepramine shows a lower risk. The highest vulnerability is seen in middle-aged and older adults (40–79 years), long-term users (>6 years), and patients with depression, cardiovascular comorbidities, or chronic pain treated with nortriptyline. Risk increases with higher doses and prolonged exposure, though acute overdose remains the most fatal scenario due to severe arrhythmias.

Key words: Tricyclic antidepressants, sudden cardiac death, antidepressant safety, cardiovascular risk, systematic review