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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Available from: Anton P Porsteinsson, Oct 03, 2015
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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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    ABSTRACT: While there have been no new medications approved for the treatment of Alzheimer's disease (AD) or other dementias in Canada since 2004, the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD) reviewed and updated the clinical practice guidelines on the pharmacological management of dementia that were published previously. This review focused on the literature for the pharmacological treatment of dementia based on studies published since the third CCCDTD in 2006. A literature search of English-language medical databases was preformed for studies pertaining to the pharmacological treatment of AD and other dementias that examined the management of cognitive and functional impairment, as well as neuropsychiatric symptoms. All previous recommendations were reviewed, and only those that required updating based on new published studies were revised. Several new recommendations were also added. Recommendations were rated for quality of evidence and were approved by consensus. There were 15 revised or new recommendations approved by consensus. The revised recommendations included acknowledging that cholinesterase inhibitors (ChEIs) possess a class effect and any of the agents can be used for AD across the spectrum of severity and with co-existing cerebrovascular disease. There was insufficient evidence to recommend for or against the use of ChEIs in combination with memantine for the primary indication of treating neuropsychiatric symptoms, or for the treatment of vascular dementia. Recommendations for the discontinuation of cognitive enhancers were revised and clarified, as well as the risks associated with discontinuing these drugs. ChEIs were recommended as a treatment option for dementia with Parkinson's disease. Risks associated with use of antipsychotics for neuropsychiatric symptoms were strengthened, and guidelines regarding the use of antidepressants for affective disturbances in dementia were weakened, and are now considered an option but not a firm recommendation. Valproate was recommended not to be used, and there was insufficient evidence to recommend for or against the use of selective serotonin reuptake inhibitors or trazodone for the treatment of agitation and aggression. In spite of the lack of new therapeutic agents for the treatment of dementia, recent studies have helped to clarify and strengthen recommendations to optimize the pharmacological management of these illnesses.
    Alzheimer's Research and Therapy 07/2013; 5(Suppl 1):S5. DOI:10.1186/alzrt201 · 3.98 Impact Factor
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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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    ABSTRACT: Depression may potentially impair the clinical course of Alzheimer's Disease (AD). Thus, the aim of this study was to investigate cognitive progression of AD patients with or without major depressive episode (MDE). In this one year longitudinal follow-up study conducted in three Italian memory clinics, 119 newly-diagnosed probable AD patients of mild severity, who were not undergoing treatment with acetyl-cholinesterase inhibitor (AChEI), and had not been treated with psychotropic drugs in the last 2years, were included. Patients were assessed to investigate the effect of baseline and one-year follow-up MDE (using modified DSM-IV diagnostic criteria for MDE in AD) on progression of global cognitive deterioration (using Mini-Mental State Examination (MMSE)), adjusted for confounding factors. Never being depressed was associated with a 3.1 (95%CI 1.0-10.1) increased risk of MMSE decline compared to recovered depression. Six times more patients with persistent depression had MMSE decline compared to patients with recovered depression. However, the largest odds (7.3; 95%CI 1.4-38.1) of cognitive decline was observed in patients who developed incident depression over follow-up. In conclusion, persistent or incident depression worsens cognitive outcome while no or recovered depression does not affect it in early AD patients.
    Psychiatry Research 03/2012; 198(2). DOI:10.1016/j.psychres.2011.11.018 · 2.47 Impact Factor
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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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    ABSTRACT: In this work we consider marketed drugs for Alzheimer disease (AD) including acetylcholinesterase inhibitors (AChE-Is) and antiglutamatergic treatment involving the N-methyl-d-aspartate (NMDA) receptor. We discuss medications and substances available for use as cognitive enhancers that are not approved for AD or cognitive impairment, and other neurotransmitter-related therapies in development or currently being researched. We also review putative therapies that aim to slow disease progression by mechanisms not directly related to amyloid or tau.
    Cold Spring Harbor Perspectives in Medicine 03/2012; 2(3):a006395. DOI:10.1101/cshperspect.a006395 · 9.47 Impact Factor
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