Depression is common in Alzheimer’s disease [AD], and antidepressants are commonly used for its treatment, yet evidence for antidepressant efficacy in this population is lacking. We conducted a multi-center, randomized, placebo-controlled trial titled “Depression in Alzheimer’s Disease-2” (DIADS-2) to assess the efficacy and tolerability of sertraline for depression in AD.
One hundred thiry-one participants from 5 U.S. medical centers with mild-to-moderate AD (Mini-Mental State Examination [MMSE] scores 10–26) and depression of AD were randomized to double-blinded treatment with sertraline (N=67) or placebo (N=64), with a target dosage of 100 mg daily. Efficacy was assessed using logistic regressions and mixed effects models in an intention to treat (ITT) analysis with imputation of missing data. Principal outcome measures were modified Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC), change in Cornell Scale for Depression in Dementia (CSDD) scores, and remission defined by both mADCS-CGIC score ≤2 and CSDD score ≤ 6.
mADCS-CGIC ratings (OR = 1.01 (95% CI: 0.52, 1.97, p=0.98), CSDD scores (median difference at 12 weeks 1.2,[95% CI -1.65, 4.05], p=0.41), and remission at 12 weeks of followup (OR = 2.06, [95% CI - 0.84, 5.04], p=0.11) did not differ between sertraline (N=67) and placebo (N=64). Sertraline-treated patients experienced more adverse events, most notably gastrointestinal and respiratory, than placebo-treated patients.
Sertraline did not demonstrate efficacy for the treatment depression symptoms in patients with Alzheimer's disease. In addition, its use was associated with an increased incidence of adverse events. Thus, selective serotonin reuptake inhibitors may be of limited value for treating depression in AD patients