{"id":572,"date":"2016-11-18T04:22:05","date_gmt":"2016-11-18T09:22:05","guid":{"rendered":"http:\/\/www.bocsci.com\/blog\/?p=572"},"modified":"2016-11-18T04:22:05","modified_gmt":"2016-11-18T09:22:05","slug":"cholinesterase-inhibitors","status":"publish","type":"post","link":"https:\/\/www.bocsci.com\/blog\/cholinesterase-inhibitors\/","title":{"rendered":"Cholinesterase Inhibitors"},"content":{"rendered":"

The \u201ccholinergic hypothesis\u201d proposes that part of age-related cognitive decline is caused by\u00a0reduced cerebral cholinergic function. This theory has been used as a\u00a0rationale for testing\u00a0drug therapies that restore cholinergic function in patients with Alzheimer’s disease (AD)\u00a0and related dementias.\u00a0Interest in the use of cholinesterase inhibitors<\/a> to manage the symptoms of AD rose\u00a0dramatically following the 1986\u00a0publication of a clinical trial of tacrine by Summers and\u00a0colleagues. Several further positive industry-sponsored clinical trials of tacrine were\u00a0published. Trials without industry sponsorship, however, failed to document similar\u00a0<\/b><\/strong>benefits with this\u00a0medication. Ultimately, the potential for serious hepatotoxicity and high\u00a0rates of intolerable adverse effects weakened enthusiasm for tacrine. While tacrine was\u00a0approved for use in the United States and in some European countries, evaluation by the\u00a0Canadian Health Protection Branch led to its rejection on the grounds that the benefits did\u00a0not translate into sufficient functional improvement to offset its potential risks. This opinion\u00a0was strengthened by an assessment that concluded that tacrine\u00a0showed no clear evidence of\u00a0efficacy or effectiveness.<\/p>\n

Other cholinesterase inhibitors that initially appeared to have benefits in the management of\u00a0AD have also been abandoned due to adverse effects. For example, metrifonate,\u00a0velnacrine,\u00a0and physostigmine never received approval for use in Canada. The drugrelated adverse events associated with this class of medications includes a variety of\u00a0gastrointestinal symptoms (such as nausea, diarrhea and weight loss), muscle weakness,\u00a0and bradyarrhythmias.<\/p>\n

Over the past few years, newer cholinesterase inhibitors have been introduced and are perceived as having fewer adverse effects. In August 1997, donepezil<\/a> became the first cholinesterase inhibitor to receive approval for use in Canada. Subsequently, rivastigmine<\/a>\u00a0and galantamine<\/a> were also given approval for use (in June 2000 and February 2001,\u00a0respectively). Numerous randomized controlled trials (RCTs) of these cholinesterase\u00a0inhibitors have demonstrated their small but significant and consistent benefits in delaying\u00a0the progressive cognitive decline associated with AD.\u00a0Aside from their efficacy, the\u00a0cholinesterase inhibitors are generally perceived to be safe. In contrast to tacrine, the newer\u00a0medications do not appear to have any significant risk of hepatotoxicity.<\/p>\n

Nonetheless, even the cholinesterase inhibitors that have been approved in Canada are
\nsubject to controversy. Many clinicians are divided over the likely real-world benefits of\u00a0these medications. The effectiveness of the cholinesterase inhibitors in most patients is\u00a0modest at best. Furthermore, the cognitive benefits wash out rapidly once the drugs are\u00a0discontinued. Roe and colleagues have suggested that adherence rates are low: 13.9% of\u00a0patients on donepezil for more than six months had gaps in treatment of six weeks or more.\u00a0Several cost-benefit analyses examining the cholinesterase inhibitors have been\u00a0presented. A recent publication suggests that donepezil may delay time to\u00a0institutionalization (which is a key assumption in the cost effectiveness models).On the\u00a0other hand, several critical systematic reviews\u00a0have argued that the finding of cost\u00a0effectiveness with these drugs is still not clear.<\/p>\n

These controversies may have contributed to delays in the addition of cholinesterase\u00a0inhibitors to provincial drug plans that provide reimbursement for medication costs to older\u00a0patients and those on social assistance. For example, although donepezil was approved for\u00a0use in Canada in 1997, it was not covered by provincial formularies until much later. In some\u00a0provinces (e.g., British Columbia), the provincial health plan still does not provide\u00a0reimbursement for any cholinesterase inhibitor. These regional differences in coverage for a\u00a0medication that typically costs $150 Canadian per month have led to dramatic differences in\u00a0the rates of cholinesterase inhibitor use across the country. The Ontario Drug Benefit\u00a0Program decided to cover donepezil in June 1999.\u00a0Coverage is provided under \u201cLimited\u00a0Use\u201d criteria: the prescribing physician must verify that patients prescribed this drug have\u00a0mild to moderate probable AD in order for them to qualify for reimbursement. Rivastigmine\u00a0and galantamine are also covered as Limited Use products under the Ontario Drug Benefit\u00a0program.<\/p>\n

 <\/p>\n

Reference:<\/p>\n

Sudeep Singh Gill. Patterns of Use and Adverse Events Associated with\u00a0Cholinesterase Inhibitors in Older Adults with Dementia<\/p>\n","protected":false},"excerpt":{"rendered":"

The \u201ccholinergic hypothesis\u201d proposes that part of age-related cognitive decline is caused by\u00a0reduced cerebral cholinergic function. This theory has been used as a\u00a0rationale for testing\u00a0drug therapies that restore cholinergic function […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[181],"tags":[225,362,363,365,364],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/572"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=572"}],"version-history":[{"count":1,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/572\/revisions"}],"predecessor-version":[{"id":573,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/572\/revisions\/573"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=572"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=572"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=572"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}