Late-life depression: evidence-based treatment and promising new directions for research and clinical practice

Abstract

As the population ages, successive cohorts of older adults will experience depressive disorders. Late-life depression (LLD) carries additional risk for suicide, medical comorbidity, disability, and family caregiving burden. Although response and remission rates to pharmacotherapy and electroconvulsive therapy are comparable with those in midlife depression, relapse rates are higher, underscoring the challenge to achieve and maintain wellness. This article reviews the evidence base for LLD treatment options and provides an analysis of treatment options for difficult-to-treat LLD variants (eg, psychotic depression, vascular depression). Treatment algorithms are also reviewed based on predictors of response and promising novel treatment options.

Fig. 1.

Comorbid anxiety symptoms and time to recurrence of late-life depression. (From Andreescu C, Lenze EJ, Dew MA, et al. Effect of comorbid anxiety on treatment response and relapse risk in late-life depression: controlled study. Br J Psychiatry 2007;190:347; with permission.)

Fig. 2.

Hierarchy of predictors of treatment response with an aggressive treatment approach. Main outcome, full response status at week 12; proportion of responders at 12 weeks, 60%. A change in HRSD score at week 4 of less than 45% from baseline predicts a less-than-half (43%) chance of responding at week 12. For the patients in this group, higher baseline anxiety predicts a 39% chance of responding at week 12. For patients with a higher baseline anxiety, a younger age of onset predicts a 32% chance of responding at week 12. (From Andreescu C, Mulsant BH, Houck PR, et al. Empirically derived decision trees for the treatment of late-life depression. Am J Psychiatry 2008;165:859; with permission.)

Fig. 3.

Hierarchy of predictors of treatment response with a conservative treatment approach. Main outcome, full response status at week 12; proportion of responders at 12 weeks, 64%. For the ATHF, a score greater than or equal to 3 indicates probably adequate antidepressant treatment history (trial of more than 4 weeks of an antidepressant at an adequate dose); ATHF les than 3 indicates inadequate antidepressant treatment history (trial of less than 4 weeks, or of more than 4 weeks but with an inadequate dose). High anxiety, at least moderate anxiety symptoms; low anxiety, mild or no anxiety symptoms. Change in HRSD at week 4 of less than 30% from baseline predicts a 35% chance of responding at week 12. For those subjects with a change in HRSD at week 4 of less than 30%, a history of at least 1 adequate antidepressant trial predicts a 13% chance of responding at week 12. For those subjects with a change in HRSD at week 4 higher than 30%, the next predictor is baseline anxiety. A higher baseline anxiety score predicts a lower chance of responding at 12 weeks (40%), whereas a lower baseline anxiety score predicts a 79% chance of responding at week 12. (From Andreescu C, Mulsant BH, Houck PR, et al. Empirically derived decision trees for the treatment of late-life depression. Am J Psychiatry 2008;165:860; with permission.)