{"id":1043,"date":"2012-07-01T00:00:48","date_gmt":"2012-07-01T07:00:48","guid":{"rendered":"http:\/\/rhochistj.org\/RhoChiPost\/?p=1043"},"modified":"2014-02-17T22:13:03","modified_gmt":"2014-02-18T05:13:03","slug":"use-donepezil-patients-delirium-without-dementia","status":"publish","type":"post","link":"https:\/\/rhochistj.org\/RhoChiPost\/use-donepezil-patients-delirium-without-dementia\/","title":{"rendered":"Use of Donepezil in Patients with Delirium (but without Dementia)"},"content":{"rendered":"

By: Lunbao (Jerry) Huang, Pharm.D. Candidate c\/o 2013<\/span><\/p>\n

–<\/p>\n

Donepezil, brand name Aricept\u00ae, is an acetylcholinesterase inhibitor indicated as monotherapy for Alzheimer’s disease, the most common form of dementia. \u00a0Cholinergic deficiency in the cortex and basal forebrain contributes to cognitive deficits in these patients. \u00a0Donepezil reversibly, noncompetitively inhibits centrally active acetylcholinesterase, the enzyme responsible for hydrolysis of acetylcholine. \u00a0This results in increased concentrations of acetylcholine available for synaptic transmission in the central nervous system. \u00a0As opposed to the chronic, slow mental digressions of Alzheimer\u2019s disease, delirium is an acute state of sudden severe confusion and rapid changes in brain function that are brought on by physical or mental illness. \u00a0Many disorders cause delirium, including conditions that deprive the brain of oxygen or vital nutrients. \u00a0Anticholinergic drugs can cause delirium in patients, thus the theory of increasing acetylcholine in the brain using acetylcholinesterase inhibitors to reverse this effect. Yet, since donepezil is only indicated for Alzheimer\u2019s disease and not for delirium, more studies were needed to evaluate the effectiveness of this treatment.<\/p>\n

In 2004, Kobayashi et al. reported a case of a 68-year-old man with a history mixed-type delirium caused by a right basal forebrain vascular lesion after surgery for craniopharyngioma.1<\/sup> \u00a0Magnetic resonance imaging showed hemorrhagic infarcts in the brain. \u00a0Treatment with antipsychotics, antidepressants, and hypnotics resulted in little improvement for this patient. \u00a0Donepezil administration dramatically improved his intractable\u00a0delirium\u00a0after 19 days of treatment; however, this was followed by amnestic symptoms. \u00a0Therefore, the clinical evidence suggests that there is a correlation between delirium\u00a0and efficacy of donepezil\u00a0treatment, which supports the hypocholinergic theory of\u00a0delirium.<\/p>\n

Within the same year, another case reported by Slatkin et al. describes successful treatment with an \u00a0acetylcholinesterase inhibitor on a 55-year-old woman with advanced ovarian cancer, severe pain, and hypoactive\u00a0delirium\u00a0caused by an increase in her opioid dosage.2<\/sup> \u00a0Intravenous physotigmine, an acetylcholinesterase inhibitor, was administered, which resulted in drastic improvements of her myoclonus and\u00a0delirium. The improvement was maintained during the administration of\u00a0oral donezepril, which is another acetylcholinesterase inhibitor.<\/p>\n

Liptzin et al. performed a relatively small study of 80 patients in a randomized, double-blind, placebo-controlled trial on using donepezil to treat delirium.3<\/sup> \u00a0Each participant was evaluated before surgery and then received\u00a0either donepezil\u00a0or placebo for 14 days before surgery and 14 days afterward. Postoperative\u00a0delirium\u00a0was assessed using Delirium\u00a0Symptom Interview, Confusion Assessment Method, daily medical record, nurse-observation reviews, and DSM-IV diagnostic criteria. \u00a0Subsyndromal\u00a0delirium\u00a0was also assessed for each participant. \u00a0There were no significant differences found between the\u00a0donepezil\u00a0and placebo groups. \u00a0When\u00a0delirium\u00a0was present, it lasted only one day. \u00a0This may suggest that postoperative\u00a0delirium\u00a0was not a major problem in this population of relatively young and cognitively-intact elderly patients undergoing elective orthopedic surgery.<\/p>\n

Similar results were seen in a pilot randomized trail in 2011by Marcantonio et al.4<\/sup> The study looked at 16 patients randomly placed in two groups to receive either donepezil\u00a0or placebo. \u00a0Treatment began at 24 hours, preoperatively or postoperatively. Daily treatment continued for 30 days or until side effects or clinical situations required termination of treatment. \u00a0The donepezil treatment group experienced more adverse effects and had no significant improvements in\u00a0delirium\u00a0presence or severity. \u00a0Overall, sufficient evidence was not found to warrant a definitive Phase III trial.<\/p>\n

Outcomes of a later randomized, double-blind, placebo-controlled trial done by Sampson et al. suggested a consistent trend towards possible benefit from donepezil treatment for patients with postoperative delirium after elective total hip replacement.4<\/sup> \u00a0This study consisted of 33 patients with 19\u00a0patients placed on donepezil, and 14 on placebo. \u00a0Donepezil\u00a0was well tolerated with no serious adverse events; however, the drug did not significantly reduce the incidence of\u00a0delirium\u00a0or length of hospital stay.\u00a0 These unsatisfactory results may be due to an insufficient number of study participants to meet adequate power; a larger sample size may be required for a more definitive trial.<\/p>\n

To date, previous studies are insufficient to suggest that donepezil is effective in treating delirium. \u00a0Most studies investigated postoperative delirium, which some suggest is reversible and does not require preventative therapy. \u00a0Patient cases do however suggest a benefit with giving donepezil in delirium. \u00a0This is an interesting prospect and a bigger, well-designed study is required to attain a definite answer.<\/p>\n

SOURCES:<\/span><\/b><\/p>\n

    \n
  1. Kobayashi K, Higashima M, Mutou K et al. Severe\u00a0delirium\u00a0due to basal forebrain vascular lesion and efficacy of\u00a0donepezil. Prog Neuropsychopharmacol Biol Psychiatry.<\/i> 2004;28(7):1189\u201494.<\/li>\n
  2. Slatkin N, Rhiner M. Treatment of opioid-induced\u00a0delirium\u00a0with acetylcholinesterase inhibitors: a case report.<\/i> J Pain Symptom Manage<\/i>. 2004;27(3):268\u201473.<\/li>\n
  3. Liptzin B<\/a>,\u00a0Laki A<\/a>,\u00a0Garb JL<\/a>,\u00a0et al. Donepezil\u00a0in the prevention and treatment of post-surgical\u00a0delirium. Am J Geriatr Psychiatry<\/i>.\u00a02005;(12):1100\u20146.<\/li>\n
  4. Sampson EL,\u00a0Raven PR,\u00a0Ndhlovu PN<\/a>, et al. A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride for reducing the incidence of postoperative delirium after elective total hip replacement. Int J Geriatr Psychiatry<\/i>. 2007;22(4):343\u20149.<\/li>\n
  5. Marcantonio ER,\u00a0Palihnich K,\u00a0Appleton P<\/a>,\u00a0et al. Pilot randomized trial of\u00a0donepezil\u00a0hydrochloride for\u00a0delirium\u00a0after hip fracture. J Am Geriatr Soc<\/i>. 2011;59(2):S282\u20148.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    By: Lunbao (Jerry) Huang, Pharm.D. Candidate c\/o 2013 – Donepezil, brand name Aricept\u00ae, is an acetylcholinesterase inhibitor indicated as monotherapy for Alzheimer’s disease, the most common form of dementia. \u00a0Cholinergic deficiency in the cortex and basal forebrain contributes to cognitive deficits in these patients. \u00a0Donepezil reversibly, noncompetitively inhibits centrally active acetylcholinesterase, the enzyme responsible for…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7,4],"tags":[75,343,58,40,198,2241,15,490,2021,13,2229,2227,803,314,342,135,601,43,361,211,363,968,1625,47,19,184,216,628,187,21,25,2252,453,1161,16,17,623,1061],"class_list":["post-1043","post","type-post","status-publish","format-standard","hentry","category-clinical","category-featured","tag-alzheimer","tag-and","tag-brain","tag-cancer","tag-daily","tag-deficiency","tag-disease","tag-donepezil","tag-double","tag-drug","tag-drugs","tag-ebola-virus-disease","tag-er","tag-for","tag-hydrochloride","tag-illness","tag-inhibitor","tag-interview","tag-mixed","tag-observation","tag-of","tag-one","tag-or","tag-pain","tag-patient","tag-problem","tag-record","tag-right","tag-side","tag-study","tag-symptom","tag-symptoms","tag-system","tag-therapy","tag-treatment","tag-trial","tag-type","tag-with"],"views":3044,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1043","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=1043"}],"version-history":[{"count":0,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1043\/revisions"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=1043"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=1043"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=1043"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}