{"id":544632,"date":"2010-04-26T17:49:40","date_gmt":"2010-04-26T21:49:40","guid":{"rendered":"http:\/\/theamazingworldofpsychiatry.wordpress.com\/?p=4414"},"modified":"2010-04-26T17:49:40","modified_gmt":"2010-04-26T21:49:40","slug":"review-retrospective-analysis-of-rivastigmine-for-alzheimer%e2%80%99s-disease-with-and-without-hallucinations","status":"publish","type":"post","link":"https:\/\/mereja.media\/index\/544632","title":{"rendered":"Review: Retrospective Analysis of Rivastigmine for Alzheimer\u2019s Disease with and without Hallucinations"},"content":{"rendered":"<p><a href=\"http:\/\/theamazingworldofpsychiatry.files.wordpress.com\/2010\/04\/rivastigmine_structural_formulae.png\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-4415\" title=\"Rivastigmine_Structural_Formulae\" src=\"http:\/\/theamazingworldofpsychiatry.files.wordpress.com\/2010\/04\/rivastigmine_structural_formulae.png?w=720&#038;h=237\" alt=\"\" width=\"720\" height=\"237\" \/><\/a><\/p>\n<p>The paper reviewed here is &#8216;Effects of Rivastigmine in Alzheimer&#8217;s Disease Patients With and Without Hallucinations&#8217; by Jeffrey Cummings and colleagues and freely available <a href=\"http:\/\/iospress.metapress.com\/content\/6675134106158v20\/fulltext.pdf\" >here<\/a>. In the abstract, the authors write that<\/p>\n<p style=\"text-align:center;\">&#8216;<strong>Hallucinations predicted greater treatment responses to oral Rivastigmine<\/strong>&#8216;<\/p>\n<p style=\"text-align:left;\">In the introduction, the researchers cite evidence that a cholinergic deficit is associated with hallucinations in Lewy Body Dementia and Parksinons&#8217; Disease with Dementia. The\u00a0 evidence of this association between cholinergic deficits and hallucinations forms the rationale for the current study where the researchers are investigating the effects of Rivastigmine on hallucinations in people with Alzheimer&#8217;s Disease.<\/p>\n<p style=\"text-align:left;\">\n<p style=\"text-align:center;\"><strong>Method<\/strong><\/p>\n<ul>\n<li>The researchers pooled data from two clinical trials although I wasn&#8217;t clear on how these studies were selected. There may be a bias towards a positive effect as unpublished negative studies may not have been included in this analysis.<\/li>\n<li>The 2 studies were randomised and placebo-controlled<\/li>\n<li>The ADAS-cog was used as a primary outcome measure<\/li>\n<li>The Clinician&#8217;s Interview based impression of Change plus Caregiver impression was also used as a primary outcome measure<\/li>\n<li>The presence of hallucinations were identified using the BEHAVE-AD (Behavioural Pathology in Alzheimer&#8217;s Disease Rating Scale) and confirmatory analysis was undertaken on the change from baseline at 26 weeks<\/li>\n<li>Physical illness was not an exclusion criteria unless severe<\/li>\n<li>Participants continued on medication for comorbid physical illness and thus the populations better approximated that which would be expected in clinical practice<\/li>\n<li>Use of psychotropic medication was an exclusion criteria (albeit with a small number of exceptions)<\/li>\n<li>Both trials were of 6 months duration<\/li>\n<li>Rivastigmine capsules with flexible dosing up to 12mg\/day in 2 divided doses were used<\/li>\n<li>The lower target dose of Rivastigmine was excluded from this analysis although I wasn&#8217;t clear on the reason for this<\/li>\n<li>The <a href=\"http:\/\/en.wikipedia.org\/wiki\/Analysis_of_covariance\" >ANCOVA<\/a> and <a href=\"http:\/\/en.wikipedia.org\/wiki\/ANOVA\" >ANOVA<\/a> were used in the statistical analysis<\/li>\n<\/ul>\n<p style=\"text-align:center;\"><strong>Results<\/strong><\/p>\n<ul>\n<li>1424 subjects were included in the analysis<\/li>\n<li>Mean age was 73.2 years<\/li>\n<li>Mean duration of dementia was 39.1 months<\/li>\n<li>23% of patients on Rivastigmine reported hallucinations at baseline<\/li>\n<li>19% of patients on placebo reported hallucinations at baseline<\/li>\n<li>The researchers write that &#8216;At 6 months, a mean improvement of 0.5 points on the ADAS-cog was seen in patients with hallucinations at baseline treated with rivastigmine, while patients without hallucinations at baseline showed a 0.3 point decline&#8217;. The improvement in ADAS-cog scores in the AD group with hallucinations was significant at below the 5% level.<\/li>\n<li>There was a greater decline in the placebo hallucinator group compared to the placebo non-hallucinator group<\/li>\n<\/ul>\n<p style=\"text-align:center;\"><strong>Discussion<\/strong><\/p>\n<p>The researchers note a small and statistically significant effect of Rivastigmine in improving ADAS-cog scores in people with AD and hallucinations. They also note an increased decline in ADAS-cog scores in the subjects with hallucinations at baseline and they speculate about the role of the basal forebrain acetylcholinergic projections. In order to further test the cholinergic hypothesis of hallucinations, I thought it would be interesting to include all acetylcholinesterase inhibitors in all forms (e.g capsules) to further explore the hypotheses generated in this paper.<\/p>\n<p style=\"text-align:center;\"><strong>Acknowledgements<\/strong><\/p>\n<p>The diagram above is by author Ju and denotes the chemical structure of Rivastigmine. The image is in the public domain and further details can be found <a href=\"http:\/\/www.google.com\/imgres?imgurl=http:\/\/upload.wikimedia.org\/wikipedia\/commons\/9\/92\/Rivastigmine_Structural_Formulae.png&amp;imgrefurl=http:\/\/commons.wikimedia.org\/wiki\/File:Rivastigmine_Structural_Formulae.png&amp;usg=__UT6YKl0cwO0sEVwHaS_tIXywoGc=&amp;h=922&amp;w=2797&amp;sz=13&amp;hl=en&amp;start=3&amp;sig2=zBgQfre_PLtfxUI1mneTqA&amp;itbs=1&amp;tbnid=6HPvzIL9EACUQM:&amp;tbnh=49&amp;tbnw=150&amp;prev=\/images%3Fq%3Drivastigmine%26hl%3Den%26gbv%3D2%26tbs%3Disch:1&amp;ei=X9rVS7bvA8ieOL29iegN\" >here<\/a>.<\/p>\n<p><strong>Call for Authors: If   you are interested in writing an  article    or series of articles for this   blog please write to the e-mail     address below. Copyright can be   retained.<\/strong> <strong>Index: <\/strong>An      index of the site  can be  found <a href=\"http:\/\/theamazingworldofpsychiatry.wordpress.com\/2010\/04\/26\/category\/index\/\" >here<\/a>. The page contains links to all of the articles                                        in the blog in chronological   order.  <strong>Twitter: <\/strong>You can  follow \u2018The Amazing World of    Psychiatry\u2019 Twitter by        clicking                              on    this\u00a0<a href=\"http:\/\/twitter.com\/TAWOP\" >link<\/a>. <strong>Podcast: <\/strong>You can listen to this post on  Odiogo by clicking on this\u00a0<a href=\"http:\/\/podcasts.odiogo.com\/the-amazing-world-of-psychiatry-a-psychiatry-blog\/podcasts-html.php\" >link<\/a> (there may be a small delay between publishing                                        of the blog article and the        availability    of     the           podcast). 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In the abstract, the authors write that &#8216;Hallucinations predicted greater treatment responses to oral Rivastigmine&#8216; In the introduction, the researchers cite evidence that a cholinergic deficit is associated with hallucinations [&hellip;]<\/p>\n","protected":false},"author":693,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[],"class_list":["post-544632","post","type-post","status-publish","format-standard","hentry","category-news"],"_links":{"self":[{"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/posts\/544632","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/users\/693"}],"replies":[{"embeddable":true,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/comments?post=544632"}],"version-history":[{"count":0,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/posts\/544632\/revisions"}],"wp:attachment":[{"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/media?parent=544632"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/categories?post=544632"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/tags?post=544632"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}