Although there are a few prospective controlled trials examining the association of de— pressive symptoms with use of a medication, most reports 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, include antiviral agents (efavirenz), cardio- vascular agents (clonidine, guanethidine, methyldopa, reserpine), retinoic acid deriva- tives (isotretinoin), antidepressants, anticonvulsants, anti-migraine agents (triptans), antipsychotics, hormonal agents (corticosteroids, oral contraceptives, gonadotropin- releasing hormone agonists, tamoxifen), smoking cessation agents (varenicline), and im- munological agents (interferon). However, other potential substances continue to emerge as new compounds are synthesized. A history of such substance use may help increase di- agnostic certainty.
Temperamental. Factors that appear to increase the risk of substance/medication- induced depressive disorder can be conceptualized as pertaining to the specific type of drug or to a group of individuals with underlying alcohol or drug use disorders. Risk fac- tors common to all drugs include history of major depressive disorder, history of drug- induced depression, and psychosocial stressors.
Environmental. There are also risks factors pertaining to a specific type of medication (e.g., increased immune activation prior to treatment for hepatitis C associated with inter- lents) of corticosteroids or high plasma concentrations of efavirenz; and high estrogen/ progesterone content in oral contraceptives.
Course modifiers. In a representative US. adult population, compared with individuals with major depressive disorder who did not have a substance use disorder, individuals with substance-induced depressive disorder were more likely to be male, to be black, to have at most a high school diploma, to lack insurance, and to have lower family income.
They were also more likely to report higher family history of substance use disorders and antisocial behavior, higher 12-month history of stressful life events, and a greater number of DSM-IV major depressive disorder criteria. They were more likely to report feelings of worthlessness, insomnia/hypersomnia, and thoughts of death and suicide attempts, but less likely to report depressed mood and parental loss by death before age 18 years.
Determination of the substance of use can sometimes be made through laboratory assays of the suspected substance in the blood or urine to corroborate the diagnosis.
and behavior from the person’s baseline, is usually temporally associated with initiation of a substance, and must be distinguished from the underlying primary mental disorders.
In regard to the treatment-emergent suicidality associated with antidepressants, a US.
99,839 participants enrolled in 372 randomized clinical 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 conclusion, suicide is clearly an extremely rare treatment-emer- gent phenomenon, but the outcome of suicide 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 ideation in patients receiving antidepressants.