Reduced Deceleration Capacity due to Tricyclic Antidepressants or NSRIs Carries an Increased Risk of sudden Cardiac Death

We read with interest the article by Okayasu et al. on the correlation of heart rate deceleration capacity (DC) in 107 patients with major depressive disorder (MDD) and bipolar disorder (BD) with doses of antidepressants or other psychotropic drugs using linear regression analysis [1] .In addition, the DC of 68 MDD patients was compared with that of 68 age-and sexmatched healthy controls [1] .The DC correlated negatively with the use of tricyclic antidepressants (TCAs) and non-tricyclic antidepressants (non-TCAs) in a dose-dependent manner, and MDD patients taking antidepressants had a significantly lower DC compared to healthy controls [1] .It was concluded that TCAs and non-TCAs cause a decrease in DC and that measuring DC may improve the predictive accuracy of sudden cardiac death (SCD) in patients taking antidepressants [1] .The study is noteworthy, but some points should be discussed.The first point is that concomitant medications other than antidepressants were not included in the analysis.Since medications other than antidepressants can also reduce DC (e.g.trastizumab, chlorpromazine, olanzapine, clozapine, zotepine) [2] , it would have been essential to exclude patients taking not only antidepressants but also other medications that reduce DC.The second issue is that comorbidities were not included in the analysis [1] .Since the effect of antidepressants on DC may strongly depend on the dosage, metabolization and excretion of the drug and its metabolites, it would have been imperative to know whether liver function and renal functions were normal or abnormal in any of the patients.Since DC may also depend on myocardial oxygenation, we should know how many of the included patients had coronary artery disease and whether those with coronary artery disease on coronary angiography or exercise testing were excluded from the analysis.It is also conceivable that reduced DC is associated with systolic dysfunction, so we should know how many of the included patients had heart failure.The autonomic functions of the heart may also depend on the presence or absence of autonomic neuropathy [3] .Therefore, we should know how many patients had a neuropathy of small or large fibers.The third point is that reduced DC is a risk factor for the development of heart failure [4] , so it would be useful to also screen individual patients with reduced DC for heart failure or systolic dysfunction.In how many of the included patients was there evidence of elevated pro-brain natriuretic peptide (pro-BNP) or reduced systolic function on echocardiography?How many patients complained of exertional dyspnoea, had leg edema or jugular vein distension?The fourth point is that there is evidence in the literature that decreased DC is associated with an increased risk of SCD [5] .We should know how many of the included patients died of asystole or malignant ventricular arrhythmias during the observation period or during follow-up?In conclusion, this interesting study has limitations that affect the results and their interpretation.Addressing these limitations could strengthen the conclusions and support the message of the study.Reduced deceleration capacity due to tricyclic antidepressants or NSRIs implies an increased risk of SCD.