Sertraline treatment is not associated with long-term improvements in mood outcomes and did not lead to any long-term benefit in non-mood neuropsychiatric symptoms, function, quality of life, or global cognition when dAD criteria were used to specify the presence of depression.
Although there was no antidepressant treatment effect, there was significant improvement for the entire study sample in mood, neuropsychiatric symptoms, and quality of life. For instance, 41% of all patients met response criteria and CSDD scores decreased on average by approximately 50% at week 24. This effect over time, in the context of a nearly 90% completion rate, suggests either non-specific therapeutic effects for being in this trial or that a substantial proportion of depressed AD patients improve with time. Including a structured psychosocial intervention for caregivers in both treatment groups may have contributed to this effect, although the response rate in the placebo group was similar to that reported in other AD antidepressant studies without such an intervention(8
Most of the improvements in mood occurred during the first 12 weeks. Among sertraline-randomized patients, the mADCS-CGIC response rate was 40% at week 12 and 45% at week 24, and remission rates were 33% at both time points. Thus there appeared little benefit overall from an additional 12 weeks of participation in the trial even though non-responders were eligible for open-label treatment during the extension phase of the study.
As studies have shown an association between depression in AD and other NPS(2
), decreased function(29
), and worse quality of life(30
), we examined whether antidepressant treatment might have a longer-term impact on any of these outcome measures. Given that patients randomized to sertraline did not have improved mood outcomes compared with placebo-randomized patients after 24 weeks, it is not surprising that sertraline treatment was not associated with improvements in these secondary outcome measures.
Acute sertraline treatment was not associated with greater impairments in global cognition at 24 weeks as assessed by the MMSE. This is consistent with the results of a metaanalysis of short-term efficacy trials for depression in AD(31
), and a retrospective study of long-term antidepressant (primarily SSRI) treatment in AD(32
). Cognitive effects might be discernable, however, on more detailed neuropsychological tests(13
The majority of sertraline-treated patients experienced diarrhea, dizziness, and dry mouth, with a 2-3 increased odds ratio. In addition, SAEs, specifically pulmonary SAEs, were more common in sertraline-randomized patients compared with placebo subjects and is consistent with a prior study(33
). Although a case-control study suggested that the risk of hospitalization for either pneumonia in general or aspiration pneumonia specifically was a confounded observation(34
), the finding here is an unbiased estimate supporting the previous observation. Overall, sertraline treatment cannot be considered to have a benign adverse event profile in AD patients.
The results of this study add to the SSRI treatment literature for depression in AD that has had as many negative as positive studies (8
). While one may consider the possibility that this clinical trial enrolled patients with chronic, treatment-resistant depression, three-quarters of study participants had no previous history of a depressive episode. SSRIs may be beneficial for the treatment of other NPS such as agitation in hospitalized AD patients(35
), warranting further study. Overall, our findings of lack of efficacy and increased adverse events combined with existing literature lead us to conclude that SSRIs cannot be recommended for the treatment of dAD. Given that depression in AD is common and associated with a range of negative outcomes, there remains an urgent need for efficacious and effective treatments for this condition.