Rosenberg PB, Drye LT, Martin BK, et al. Sertraline for the treatment of depression in Alzheimer disease

Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry (Impact Factor: 4.24). 02/2010; 18(2):136-45. DOI: 10.1097/JGP.0b013e3181c796eb
Source: PubMed


Depression is common in Alzheimer disease (AD), and antidepressants are commonly used for its treatment, however, evidence for antidepressant efficacy in this population is lacking. The authors conducted a multicenter, randomized, placebo-controlled trial titled "Depression in Alzheimer's Disease-2" to assess the efficacy and tolerability of sertraline for depression in AD.
One hundred thirty-one participants from five U.S. medical centers with mild-to-moderate AD (Mini-Mental State Examination 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 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 <or=2 and CSDD score <or=6.
mADCS-CGIC ratings (odd ratio [OR = 1.01], 95% confidence interval [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 follow-up (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 AD. 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 patients with AD.

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    • "Since then, two large RCTs on the treatment of depression in dementia have shown benefits equivalent to placebo. Using the provisional diagnostic criteria for depression in AD [72], the DIADS-2 study compared 131 patients randomized to sertraline or placebo for 12 weeks [73]. Both groups experienced significant and similar reductions in depressive symptoms, although the sertraline-treated group experienced more adverse events. "
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    • "Further, our results highlight the importance of considering the disadvantages and advantages of anti-depressant treatment in these patients, especially as both the depression itself, and the cognitive progression of AD, may be affected by such medications. In fact, in a general context of conflicting data between positive and negative effects of antidepressants (Rosenberg et al., 2010), it has also been reported that some SSRI may improve depressive symptoms (Lyketsos et al., 2003) and may be associated with cognitive benefits (Chow et al., 2007; Rozzini et al., 2010). From the perspective of patients and caregivers, research identifying factors that influence cognitive progression of AD may help in long-term planning of care. "
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    • "Strategies for use of antipsychotics in patients with AD involve avoiding their use in patients with cardiovascular or pulmonary disease (the two most common causes of death in mortality studies), using these agents only in patients for whom nonpharmacologic interventions have failed and the behaviors are extreme, employing treatment for only the period required and attempting to eliminate the agents as soon as possible, and informing the patient and caregiver of the risks involved. 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. "
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