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Depression worsens the course of dementia, but evidence for the effectiveness of antidepressants in patients with these illnesses is sparse and inconsistent. This large, randomized, controlled, 39-week, treatment trial involved 326 patients with possible or probable Alzheimer disease, who were mostly community-dwelling and had sought care for depression at one of nine U.K. “old-age psychiatry services” (Cornell Scale for Depression in Dementia [CSDD] score, ≥8; mean score on the Mini Mental State Exam, 18).
Treatments were sertaline, mirtazapine, or placebo; doses were increased at 4 and 8 weeks if CSDD scores did not decrease to below 4. Completion rates were 79% at 13 weeks (acute phase) and 69% at 39 weeks (mean doses among completers: sertraline, 95 mg; mirtazapine, 30 mg). Depression scores improved similarly in all three groups over the course of the study. Secondary measures (e.g., caregivers' mental health) showed few consistent between-group differences. In contrast, both medications were associated with more adverse reactions than placebo, and sertraline produced more neuropsychiatric symptoms and less improvement in carer-rated quality of life than mirtazapine at 13 weeks.
Banerjee S et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): A randomised, multicentre, double-blind, placebo-controlled trial. Lancet 2011 Jul 30; 378:403.
Comment
This study of antidepressant effectiveness in patients with dementia is as large as all such previous trials combined. The trial enrolled representative patients, had good retention, included a broad range of Alzheimer disease, and tested antidepressants from the two most-used classes, which have distinct mechanisms of action and adverse effect profiles. Additional aspects of usual care offered by the U.K. specialty clinics might account for the overall improvement. The authors recommend stepped care for depression in dementia patients — an initial 3 months of watchful waiting/low-intensity psychosocial treatment followed by more-complex psychosocial interventions. Antidepressants should probably be reserved for severely depressed patients, those failing initial steps of care, and, perhaps, those with other behavioral symptoms such as agitation.