prescribed treatment for a mental disorder or another medical condition) must have its on-
set while the individual is using the substanc e or during withdrawal, if there is a with-
drawal syndrome associated with the substanc e. Most often, the de pressive disorder has
its onset within the first few weeks or 1 month of use of the substance. Once the substance
is discontinued, the depressive symptoms usually  remit within days to several weeks, de-
pending on the half-life of the substance/medication and the presence of a withdrawal
syndrome. If symptoms persist 4 weeks beyond the expected time course of withdrawal of
a particular substance/medi cation, other causes for th e depressive mood symptoms
should be considered.
Although there are a few prospective controlle d trials examining the association of de-
pressive symptoms with use of a medication, most report s are from postmarketing sur-
veillance studies, retrospective observational studies, or case  reports, making evidence of
causality difficult to determine. Substances implicated in medication-induced depressive
disorder, with varying degrees of evidence, in clude antiviral agents (efavirenz), cardio-
vascular agents (clonidine, guanethidine, me thyldopa, reserpine), re tinoic acid deriva-
tives (isotretinoin), antidepressants, antico nvulsants, anti-migraine agents (triptans),
antipsychotics, hormonal agents (corticost eroids, oral contrace ptives, gonadotropin-
releasing hormone agonists, tamoxifen), smoking cessation agents (varenicline), and im-
munological agents (interferon) . However, other potential su bstances continue to emerge
as new compounds are synthesized. A history of  such substance use may help increase di-
agnostic certainty.