Two antidepressants ineffective for depression in patients with dementia

Sertraline (Zoloft) or mirtazapine (Remeron) was not better than placebo for depression in Alzheimer's disease, and both drugs are associated with higher rates of nausea and drowsiness, a British study found.

Researchers conducted a parallel-group, double-blind, randomized, placebo-controlled study, the Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD), in patients using geriatric psychiatry services in nine centers. Participants were eligible if they had probable or possible Alzheimer's disease, depression (lasting more than 4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more.

Patients received sertraline (150 mg/d), mirtazapine (45 mg), or placebo, all with standard care. The primary outcome was reduction in CSDD score at 13 weeks. Results appeared at The Lancet on July 19.

Severity of depression decreased in all three intervention groups compared with baseline. The greatest absolute improvement in CSDD scores at 13 weeks occurred with placebo (−5.6; SD, 4.7), compared with sertraline (−3.9; SD, 5.1) and mirtazapine (−5.0; SD, 4.9). At 39 weeks, recovery from baseline was sustained for placebo (−4.8; SD, 5.5), sertraline (−4.0; SD, 5.2) and mirtazapine (−5.0, SD, 6.1).

Overall, decreases in depression scores at 13 weeks did not differ between the 111 controls and 107 participants allocated to receive sertraline (mean difference, 1.17; 95% CI, −0.23 to 2.58; P=0.10) or mirtazapine (mean difference, 0.01; 95% CI, −1.37 to 1.38; P=0.99), or between participants in the mirtazapine and sertraline groups (mean difference, 1.16; 95% CI, −0.25 to 2.57; P=0.11).

Gastrointestinal reactions, usually nausea, were most common with sertraline. Psychological reactions, usually drowsiness and sedation, were most common with mirtazapine. At 13 weeks, there were 15 serious adverse events in the placebo group, three severe, compared to 12 in the sertraline group, eight severe, and 14 in the mirtazapine group, 10 severe. While the number of serious events did not differ among the groups, more of these events were severe in those on antidepressants compared with placebo (P=0.003).

“Analysis of the data suggests clearly that antidepressants, given with normal care, are not clinically effective when compared with placebo for the treatment of clinically significant depression in dementia,” the authors concluded. “This finding implies a need to change the present clinical practice of prescription of antidepressants as the first line treatment of depression in dementia caused by Alzheimer's disease.”

They suggested that because many cases resolve with usual care and without drugs as a first-line therapy, stepped care with watchful waiting is advocated for the community treatment of depression without dementia. The first step is low-intensity psychosocial interventions, with more complex psychosocial interventions as an alternative to antidepressants as severity increases. Antidepressants might be reserved for those whose depression has not resolved within three months, “apart from those in whom drug treatment is indicated by risk or extreme severity,” the authors wrote.