Pariente A, Fourrier-Reglat A, Bazin F, et al. Effect of treatment gaps in elderly patients with dementia treated with cholinesterase inhibitors

University Bordeaux Segalen, Bordeaux, France.
Neurology (Impact Factor: 8.29). 03/2012; 78(13):957-63. DOI: 10.1212/WNL.0b013e31824d5773
Source: PubMed


To determine the effect of treatment gaps on the risk of institutionalization or death among community-dwelling elderly patients treated with cholinesterase inhibitors (ChIs).
A survival analysis was conducted among a cohort of community-dwelling elderly patients (age 66+) newly treated with ChIs identified in the Quebec drug claims databases (Régie de l'Assurance Maladie du Québec [RAMQ]) between January 1, 2000, and December 31, 2007. Treatment nonpersistence during the year following ChI initiation was defined as treatment discontinuation or gaps of at least 6 weeks. To account for reverse causality, Cox proportional hazard modeling was conducted only among patients who did not discontinue treatment, in order to assess the association between treatment nonpersistence and institutionalization or death.
Among the 24,394 elderly ChI users, 4,108 (16.8) experienced a treatment gap during the year following ChI treatment initiation while 596 (2.4%) discontinued their treatment within the first 3 months (early stoppers) and 4,038 (16.6%) after 3 months of treatment (late stoppers). Of all treated patients, 4,409 (18.1%) were institutionalized or died during follow-up. In patients who did not stop their treatment, the risk of institutionalization or death appeared lower in patients who experienced a treatment gap (hazard ratio 0.91; 95% confidence interval 0.86-0.96).
Our results suggest that, contrary to what was previously reported in clinical trials, treatment gaps do not compromise the outcome of patients treated with ChIs in a real-life setting.

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    ABSTRACT: In this article, we discuss new data on currently licensed drugs for dementia and novel developments in the management of neuropsychiatric symptoms in patients with dementia. During the last years, a large body of evidence has been accumulated to support the use of antidementia medication in patients with severe Alzheimer's disease. Combination therapy with acetylcholinesterase inhibitors and memantine for Alzheimer's disease remains controversial, as controlled trials have yielded conflicting results. Memantine is not indicated in patients with mild Alzheimer's disease. Studies on memantine for Parkinson's disease dementia and dementia with Lewy bodies were inconclusive. In adult patients with dementia in the context of Down syndrome, memantine is not effective, and further studies on acetylcholinesterase inhibitors are warranted. There is still no treatment established for patients with vascular or frontotemporal dementia. The efficacy of antidepressants to treat depression associated with dementia is not proven. Treatment of agitation and psychosis in patients with dementia remains a challenge. Recent systematic clinical reviews and new research on currently available treatment options provide valuable assistance for clinicians to deal with frequent clinical problems in the context of dementia.
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    ABSTRACT: Pariente et al.(1) concluded that "Treatment gaps do not compromise the outcome of patients treated with cholinesterase inhibitors in a real-life setting." However, their conclusion is based on the effect of treatment gaps on risk of institutionalization and death, rather than on disease-specific endpoints. It has been shown that the beneficial effect of cholinesterase inhibitors on cognition, an important disease-specific endpoint, disappears within 3 weeks of discontinuation.(2,3) In addition, as mentioned by Pariente et al., treatment gaps are likely to occur in patients in whom reinitiation of treatment is worthwhile. From this, we infer that selection may have played a role, consequently limiting the generalizability of the study to a real-life setting.(4) This study is welcome because the authors address an important issue. However, because of these caveats, clinicians should not discontinue treatment too readily, as discontinuation of treatment does affect cognition, thereby compromising the outcome of patients.
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