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Quetiapine and Rivastigmine Not Often Helpful for Agitation in Alzheimer's Disease

  • Authors: News Author: Laurie Barclay, MD
    CME Author: Charles Vega, MD, FAAFP
  • CME Released: 2/22/2005
  • Valid for credit through: 2/22/2006
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Target Audience and Goal Statement

This article is intended for primary care physicians, geriatricians, psychiatrists, neurologists, and other specialists who care for patients with dementia.

The goal of this activity is to provide the latest medical news to physicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  • Identify predictors of rapid cognitive decline in patients with dementia.
  • Describe the efficacy of quetiapine and rivastigmine in outcomes of behavior and cognition among patients with severe dementia.


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  • Laurie Barclay, MD

    Laurie Barclay is a freelance reviewer and writer for Medscape.


    Disclosure: Dr. Barclay has reported no significant financial interests.


  • Gary Vogin, MD

    Senior Medical Editor, Medscape


    Disclosure: Dr. Vogin has reported no significant financial interests.

CME Author(s)

  • Charles P Vega, MD

    Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine


    Disclosure: Dr. Vega has disclosed that he has received grants for educational activities from Pfizer.

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Quetiapine and Rivastigmine Not Often Helpful for Agitation in Alzheimer's Disease

Authors: News Author: Laurie Barclay, MD CME Author: Charles Vega, MD, FAAFPFaculty and Disclosures

CME Released: 2/22/2005

Valid for credit through: 2/22/2006


Feb. 22, 2005 — Neither quetiapine nor rivastigmine help with agitation in Alzheimer's disease, and quetiapine is associated with greater decline in cognitive function than placebo, according to the results of a randomized study in the Feb. 17 Online First issue of the BMJ. The investigators recommend against using quetiapine in this setting.

"Antipsychotic drugs are commonly prescribed to many people with dementia (up to 45%) in residential or nursing homes, often for prolonged periods," write Clive Ballard, MD, from King's College in London, U.K., and colleagues. "Antipsychotics have modest efficacy but are commonly associated with substantial adverse effects such as parkinsonism, tardive dyskinesia, reduced quality of life, and cardiac arrhythmias. More seriously, an increased risk of stroke has been reported in patients taking the two most widely prescribed atypical antipsychotics, risperidone and olanzapine."

In this double-blind trial performed at health care facilities in northeast England, 93 patients with Alzheimer's Disease, dementia, and clinically significant agitation were randomized to receive quetiapine (an atypical antipsychotic), rivastigmine (a cholinesterase inhibitor), or placebo (double dummy). The primary outcome was the Cohen-Mansfield agitation inventory score at six weeks, and secondary outcomes were agitation at 26 weeks and cognition (severe impairment battery) at six and 26 weeks.

Of 80 patients (N = 93; 86%) who started treatment, 25 (31%) were randomized to rivastigmine, 26 (32%) to quetiapine, and 29 (36%) to placebo. Of 71 patients (N = 93; 89%) who tolerated the maximum protocol dose, 22 (31%) were assigned to rivastigmine, 23 (32%) to quetiapine, and 26 (37%) patients to placebo. Compared with placebo, neither quetiapine nor rivastigmine showed significant differences in improvement on the agitation inventory either at six or 26 weeks.

Of 50 patients who scored more than 10 on the severe impairment battery at baseline, 46 patients (82%) were included in the analysis at six-week follow-up, including 14 assigned to rivastigmine, 14 to quetiapine, and 18 to placebo. For quetiapine, the change in severe impairment battery score from baseline worsened vs placebo by an estimated average of -14.6 points (95% confidence interval [CI], -25.3 to -4.0) at six weeks ( P = .009) and -15.4 points (95% CI, -27.0 to -3.8) at 26 weeks ( P = .01). For rivastigmine, the corresponding changes were -3.5 points (95% CI, -13.1 to 6.2) lower at six weeks ( P = .5) and -7.5 points (95% CI, -21.0 to 6.0) lower at 26 weeks ( P = .30).

"Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care," the authors write. "Compared with placebo, quetiapine is associated with significantly greater cognitive decline."

Study limitations include modest sample size, multiple evaluations, and the substantial proportion of patients who were unable to complete the severe impairment battery.

"Given current concerns about the risk of stroke with risperidone and olanzapine, further studies are required to enable evidence-based pharmacological management of behavioural disturbance in dementia," the authors conclude. "Our results suggest that quetiapine should not be used as an alternative treatment to risperidone or olanzapine in people with dementia and highlight concerns regarding the long term use of antipsychotics in these patients."

The Alzheimer's Research Trust helped support this study, which was funded largely from general donations to Dr. Ballard's research and profits from previously completed commercially funded clinical trials. Dr. Ballard has received honoraria and research donations from AstraZeneca, maker of quetiapine, and Novartis, maker of rivastigmine.

BMJ. Posted online Feb. 17, 2005.