Final answer:
Cardiotoxicity is the most serious and potentially lethal adverse effect of TCAs, particularly in cases of overdose.
Step-by-step explanation:
The most serious adverse effect of TCAs, or tricyclic antidepressants, which can be lethal if an overdose occurs, is cardiotoxicity. Tricyclic antidepressants are known to inhibit the reuptake of neurotransmitters such as epinephrine and serotonin, which can have anti-anxiety and antidepressant effects. However, due to their side effects and the potential for a fatal overdose, TCAs are now seldom used. The cardiotoxic effects can include severe heart function impairment, leading to arrhythmias, which are a potentially lethal outcome of an overdose.