Sertraline for the Treatment of Depression in Alzheimer Disease: Week-24 Outcomes

Abstract

Background Depression and antidepressant use are common in Alzheimer’s disease (AD), but the effect of antidepressant treatment for depression on longer-term outcomes is unknown. We report the week-24 outcomes of patients who participated in a 12-week efficacy study of sertraline for depression of AD. Methods 131 participants (sertraline=67, placebo=64) with mild-moderate AD and depression participated in the study. Patients who showed improvement on the modified Alzheimer’s Disease Cooperative Study Clinical Global Impression-Change (mADCS-CGIC) after 12 weeks of randomized treatment with sertraline or placebo continued double-blinded treatment for an additional 12 weeks. Depression response and remission at 24 weeks were based on mADCS-CGIC score and change in Cornell Scale for Depression in Dementia (CSDD) score. Secondary outcome measures included time to remission, non-mood neuropsychiatric symptoms, global cognition, function, and quality of life. Results 117 (89.3%) participants completed all study assessments and 74 (56.5%; sertraline=38, placebo=36) completed all 24 weeks on randomized treatment. By 24 weeks, there were no between-group differences in depression response (sertraline=44.8%, placebo=35.9%; odds ratio [95% CI]=1.23 [0.64, 2.35]), change in CSDD score (median difference=0.6 [95% CI −2.26, 3.46], χ2 [df=2]=1.03), remission rates (sertraline=32.8%, placebo=21.8%; odds ratio [95% CI]=1.61 [0.70, 3.68]), or secondary outcomes. Common SSRI-associated adverse events, specifically diarrhea, dizziness, and dry mouth, and pulmonary serious adverse events (SAEs) were more frequent in sertraline-randomized patients than in placebo subjects. Conclusions Sertraline treatment is not associated with delayed improvement between 12 and 24 weeks of treatment and may not be indicated for the treatment of depression of AD.

Symptomatic and Nonamyloid/Tau Based Pharmacologic Treatment for Alzheimer Disease

“…Clinical trials have been largely negative in showing benefit for treatment of depression in AD with antidepressant medications (Lyketsos et al 2000;Olin et al 2002;Rosenberg et al 2010;Weintraub et al 2010). There is no consistent evidence base for the use of antidepressants in AD.…”

Patterns of psychotropic prescribing and polypharmacy in older hospitalized patients in Ireland: the influence of dementia on prescribing

“…However, antipsychotics are known to increase the risk of stroke and mortality in PwD (Schneider et al, 2005), and a recent study has found that for every 26 PwD treated with haloperidol, there was one death (Maust et al, 2015). Additionally, the DIADS-2 trial found that sertraline was not efficacious for the treatment of depression in PwD and was associated with an increased risk of adverse events (Rosenberg et al, 2010;Weintraub et al, 2010). Guidelines generally recommend that nonpharmacological treatments should be used as firstline treatment of BPSD, and only when these fail should psychotropic agents be trialed for shortterm use (Azermai et al, 2012).…”

Depression in Alzheimer’s disease: consequence or contributing factor?

“…No differences in cognitive function were noted between participants receiving drug or placebo. Furthermore, there was no difference in response from those subjects who met the criteria of major depression in addition to depression of Alzheimer's disease [9][10][11]. These disappointing results unfortunately generate more questions than answers.…”