Coexisting anxiety tends to be associated with more severe illness, greater risk of suicide and poorer response to antidepressant treatment. In such circumstances, the presence of complaints such as depressed mood, loss of interest and pleasure, feelings of worthlessness and guilt, and suicidal ideation should tip the diagnostic balance in favor of major depression. Recognizing the core illness as depression, despite the sometimes seductive overtones of anxiety, has critical therapeutic implications. Despite the absence of a prominent sedative effect, treatment of the core depressive illness with these drugs led to resolution of the associated anxiety symptoms. A confounding factor in these studies is that SSRIs do cause sedative side effects in some patients.
Proper consideration needs to be given to the timely discontinuation of the second drug.
When all else fails, common sense provides a good basis for action. At one extreme, a depressed patient with severe psychomotor retardation and hypersomnia is probably not the best candidate for a sedating antidepressant. At the other extreme, a highly anxious, agitated patient with severe insomnia is probably not the ideal recipient of monotherapy with a nonsedating antidepressant. This said, I suspect that studies comparing a sedating to a nonsedating antidepressant in either of these patient profiles would have similar outcomes at study end, although there may well be differences in how well these drugs are tolerated early in the course of therapy. Since antidepressant response is usually measured over weeks rather than days, one should not underestimate the value of interventions that can provide prompt relief of anxiety symptoms.