and behavior from the person’s baseline, is us ually temporally associated with initiation of
a substance, and must be distinguished from  the underlying prim ary mental disorders.
In regard to the treatment-emergent suicida lity associated with antidepressants, a U.S.
Food and Drug Administration (FDA) adviso ry committee considered meta-analyses of
99,839 participants enrolled in 372 randomized clin ical trials of antidepressants in trials for
mental disorders. The analyses  showed that when the data were pooled across all adult
age groups, there was no perceptible increased risk of suicidal behavior or ideation. How-
ever, in age-stratified analyses , the risk for patients ages 18–24 years was elevated, albeit
not significantly (odds ratio [OR] = 1.55; 95%  confidence interval [CI] = 0.91–2.70). The
FDA meta-analyses reveal an absolute risk of suicide in patients taking investigational an-
tidepressants of 0.01%. In conc lusion, suicide is clearly an extremely rare treatment-emer-
gent phenomenon, but the outcome of suicid e was serious enough to prompt the FDA to
issue an expanded black-box warning in 2007 regarding the importance of careful moni-
toring of treatment-emergent suicidal ideati on in patients receiving antidepressants.
Differential Diagnosis
Substance intoxication and withdrawal. Depressive symptoms occur commonly in sub-
stance intoxication and substance withdrawal, and the diagnosis of the substance-specific
intoxication or withdrawal will usually suffice to categorize the symptom presentation. A
diagnosis of substance-induced depressive di sorder should be made  instead of a diag-
nosis of substance intoxicati on or substance withdrawal when the mood symptoms are
sufficiently severe to warrant independent clinical attention. For example, dysphoric