The decision made in the year 2004 by the U.S. Food and Drug Administration 
(FDA) to require a boxed warning on antidepressants regarding the risk of 
suicidality in young adults still represents a matter of controversy. The FDA 
warning was grounded on industry-sponsored trials carried one decade ago or 
earlier. However, within the past decade, an increasing number of reports have 
questioned the actual validity of the FDA warning, especially considering a 
decline in the prescription of the antidepressant drugs associated with an 
increase in the rate of suicidal events among people with severe depression. The 
present report provides an overview of the FDA black box warning, also 
documenting two Major Depressive Disorder patients whose refusal to undergo a 
pharmacological antidepressant treatment possibly led to an increased risk for 
suicidal behaviors. The concerns raised by the FDA black box warning need to be 
considered in real-world clinical practice, stating the associated clinical and 
public health implications.