A number of recent randomized, controlled trials have examined the treatment of depression in older adults. Comparisons of several SSRIs with the tricyclic antidepressant nortriptyline show better tolerability with SSRIs in this group of patients (135–137). Although the efficacies of nortriptyline and SSRIs generally appear to be comparable (135, 136), some data suggest that nortriptyline may be more effective in severely depressed individuals (137). An additional randomized, controlled outpatient trial showed comparable efficacy for two SSRIs, sertraline and fluoxetine, in the acute treatment of major depression (138).

Maintenance antidepressant therapy is associated with a lesser likelihood of relapse in older adults (139, 140). These data extend the findings of Reynolds et al. (141), discussed in the guideline, which showed antidepressant medication (nortriptyline) or interpersonal therapy to be effective maintenance therapy for elderly patients with recurrent major depressive disorder.

In the PROSPECT study (142), in which elderly patients were treated in primary care practices with facilitation by case managers, interventions included treatment with an antidepressant (typically citalopram) and interpersonal psychotherapy (for patients who declined antidepressant). Compared with treatment as usual, intervention was associated with more rapid and more prominent reductions in suicidal ideation and depressive symptoms, and the beneficial impact on depression extended throughout the 12-month study period. Although not all patients in the intervention group continued to receive treatment for depression throughout the study period, a greater proportion of intervention patients received ongoing treatment compared with the treatment-as-usual group, strengthening the observation that maintenance treatment is beneficial in depressed older adults.

Several studies have compared antidepressant treatment, nonpharmacological treatments, or combined treatments in older adults. Blumenthal et al. (143) found comparable rates of response in older depressed patients randomly assigned to treatment with sertraline, aerobic exercise, or combination treatment. After 10 months, greater sustained benefit was seen in the exercise-alone group, whereas response rates in the sertraline-alone and sertraline-plus-exercise groups were comparable (71). Thompson et al. (144) showed combination treatment with desipramine and CBT to be better than desipramine alone, comparable to CBT alone, and of particular benefit in elderly outpatients who were severely depressed. These findings supplement those of Reynolds et al. (141), who showed a trend for superior acute response with combined nortriptyline and interpersonal therapy. With maintenance treatment, either therapy was effective in rapid responders to treatment, but combined treatment was superior in patients who had a mixed or delayed response to initial therapy (139). In addition, combination therapy was more effective in maintaining social adjustment than either therapy alone (145).