Antidepressants cause bradycardia and heart block in GD 13 rat embryos in vitro

Abstract

This study investigated the effects of a range of antidepressant drugs on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the drugs would adversely affect the function of the embryonic heart since they all have some cardiac ion channel blocking activity in addition to their main pharmacological effect on neurotransmitters. The results showed that all the tested drugs caused bradycardia in a generally concentration-dependent manner. At higher concentrations most of the drugs caused some degree of heart block consistent with sodium channel blockade and some drugs also showed negative inotropy associated with blockade of the L-type calcium channel. One drug, trazodone, caused arrhythmia consistent with blockade of the hERG (human ether-a-go-go related gene) potassium channel. In general the effects on the embryonic rat heart were only seen at "free drug" concentrations much greater than those likely to occur in pregnant women taking antidepressant medication. The least margin of safety was seen with the tricyclic antidepressants and the serotonin antagonist and reuptake inhibitor trazodone.