Which of the following antidepressants is least likely to be lethal in overdose?

SSRIs, or selective serotonin reuptake inhibitors, are generally considered to be the least lethal antidepressants in the event of an overdose. This lower lethality can be attributed to their mechanism of action and side effect profile. Unlike tricyclic antidepressants (TCAs), which can cause fatal arrhythmias and have significant anticholinergic effects in overdose situations, SSRIs primarily increase serotonin levels without the same degree of cardiovascular risks.

While MAOIs (monoamine oxidase inhibitors) can also lead to serious and potentially fatal interactions, particularly with tyramine-rich foods and other medications, they are not as commonly associated with lethal outcomes from overdose when compared to TCAs. Moreover, SSRIs generally have a wider therapeutic index, meaning the gap between the therapeutic dose and a potentially harmful dose is larger, making them safer.

By understanding the specific risks associated with different classes of antidepressants, it's clear why SSRIs are preferred in terms of safety during overdose scenarios. This is a critical factor in clinical decision-making when prescribing antidepressants, particularly for patients who may be at risk for suicide.