1、實實證醫學個案討論證醫學個案討論急診內科何英豪醫師95-10-181Q:一位76歲的男性患有輕度阿茲海默症，但未服用任何藥物。他的兒子帶他來門診就診，想要了解銀杏治療失智症的療效。2PICOnP:Alzheimers diseasenI:Gingko bilobanC:nO:Effect3Search terms&StrategynKeyword:Gingko,Alzheimers diseasenDatabase:PubMednSearch strategy:Gingko:1414 A.D.:50043 Gingko and A.D.:134 +English,Chinese,Human,A
2、bstract:67 +Clinical Trial,Meta-analysis,RCT:154Oxford Centre for EBM Levels of Evidence(2001-5)n1a:SR(with homogeneity)of RCTs.n1b:Individual RCT(with narrow confidence interval).n2a:SR(with homogeneity)of cohort studiesn2b:Individual cohort study(low quality RCT;80%follow-up)n3a:SR(with homogeneit
3、y)of case-control studies.n3b:Individual case-control study.n4:Case-series(poor quality cohort and case-control studies).n5:Expert opinion without explicit critical appraisal,or based on physiology,bench research or“first principles”5Ginkgo biloba and donepezil:a comparison in the treatment of Alzhe
4、imers dementia in a randomized placebo-controlled double-blind study Eur J Neurol 2006 Level:Ib n24-week randomized,placebo-controlled,double-blind study.nAged 50-80years,mild to moderate dementianGinkgo biloba(160 mg daily dose),donepezil(5 mg daily dose),or placebo group.nNo evidence of relevant d
5、ifferences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimers dementia,so the use of both substances can be justified.6A randomized,double-blind,placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimers type.Curr Alzheimers Res
6、.2005 Level:Ib nRandomized,placebo-controlled,double-blind,parallel-group,multicenter trial n513 outpatients with uncomplicated dementia of the Alzheimers type scoring 10 to 24 on MMSE and less than 4 on the modified Hachinski Ischemic Score.n26-week treatment with GbE at daily doses of 120 mg or 24
7、0 mg or placebonThe trial did not show efficacy of GbE,however,the lack of decline of the placebo patients may have compromised the sensitivity of the trial to detect a treatment effect.nThus,the study remains inconclusive with respect to the efficacy of GbE.7The situation of patients with dementia
8、may be rectified by Ginkgo biloba.Results of a health services research study concerning the ability of patients with dementia,quality of life of the nursing family members and total treatment costs MMV Fortschr Med 2005 Level:IIb(?)nNon-randomised,two-armed cohort study with an open design n683 sli
9、ghtly or moderately demented patients,etween 65 and 80 years.nQuality-of-life of care-taking relatives(p 0.001)in the Ginkgo-cohort.nBarthel-Index in the Ginkgo-cohort(p or=0,001).n3.614,75 euro in the standard-cohort,3.031,78 euro in the Ginkgo-cohort(p=0.067).nGinkgo treatment has a valid place in
10、 caretaking structure of health services.nGingko attributes to a higher quality of life for both care-takers and patients,the progression of disease is slowed down and treatment costs are lower.8Ginkgo biloba compared with cholinesterase inhibitors in the treatment of dementia:a review based on meta
11、-analyses by the Cochrane collaboration.Dement Geriat Cogn Disord 2004 Level:Ia nCochrane Collaboration meta-analyses of ginkgo,donepezil,rivastigmine and galantamine in patients with dementia.n6 months of treatmentnTrial data for cholinesterase inhibitors were more consistent than those for ginkgo,
12、particularly regarding patient populations and outcome measures.nSignificant benefits on cognition vs.placebo were seen with donepezil,5 and 10 mg,rivastigmine,6-12 mg,and galantamine,16 and 24 mg.nSignificant benefit vs.placebo with ginkgo was seen only when all doses were pooled.Similar proportion
13、s of patients discontinued treatment with ginkgo and placebo.nCholinesterase inhibitors were also well tolerated,although a significantly greater proportion of patients receiving active treatment discontinued vs.placebo with some doses.9Ginkgo biloba extract EGb 761 in dementia:intent-to-treat analy
14、ses of a24-week,multi-center,double-blind,placebo-controlled,randomized trial.Pharmacopsychiatry 2003 Level:Ib nGinkgo biloba special extract EGb 761(240 mg/day)in outpatients with pre-senile and senile primary degenerative dementia of the Alzheimer type(DAT)and multi-infarct dementia(MID)of mild to
15、 moderate severity.nDouble-blind,placebo-controlled,randomized,multi-center study nThe results of this ITT analysis substantiate the outcomes previously obtained with a responder analysis of the per-protocol population and confirm that EGb 761 improves cognitive function in a clinically relevant man
16、ner in patients suffering from dementia.10Response patterns of EGb 761 in Alzheimers disease:influence of neuropsychological profiles.Pharmacopsychiatry 2003 Level:Ib n52-week,randomized,double-blind,placebo-controlled study with 120 mg EGb 761 based on cut-off points applied to Alzheimers Disease.n
17、Retrospective analysis of overall efficacy indicated that a quantitative treatment effect favorable to EGb 761 could be observed in cognitive performance(p=0.04)and social functioning(p=0.02).11Association of Alzheimers disease onset with ginkgo biloba and other symptomatic cognitive treatments in a
18、 population of women aged 75 years and older from the EPIDOS study.J Gerontol A Biol Sci Med Sci.2003 Level:Ib nPeripheral C4A treatment(cerebral and peripheral vasotherapeutics)and especially Ginkgo biloba extracts are prescribed for memory impairment,in elderly patients.nCase-control study of 1462
19、 community-dwelling elderly women aged over 75 years.n69 women with Alzheimer-type dementia were compared with 345 paired women whose cognitive function remained normal.n7-year follow-up period.nA multivariate analysis showed that fewer women who developed Alzheimers dementia had been prescribed C4A
20、 treatment(including EGb 761)for at least 2 years(odds ratio=0.31,95%confidence interval=0.12-0.82,p=.018).nThese results suggest that C4A treatment may reduce the risk of developing Alzheimers dementia in elderly women.12Influence of the severity of cognitive impairment on the effect of the Gnkgo b
21、iloba extract EGb 761 in Alzheimers disease.Neuropsychobiology 2002 Level:Ib n52-week,randomized,double-blind,placebo-controlled,parallel-group,multicenter study with 120 mg of EGb,using cutoff points of 23 and 14 for MMSE score.nTreatment effect favorable to EGb could be observed with respect to co
22、gnitive performance(p=0.02)and social functioning(p=0.001)regardless of the stage of dementia,whether mild or moderately severe.nImprovement in the group of patients with very mild to mild cognitive impairment.nIn more severe dementia,the mean EGb effect should be considered more in terms of stabili
23、zation or slowing down of worsening,as compared to the greater deterioration observed with placebo 13Cholinesterase inhibitors and Gingko extracts-are they comparable in the treatment of dementia?Comparison of published placebo-controlled efficacy studies of at least six months duration.Phytomedicin
24、e 2000 Level:Ia(?)nThe efficacy of four cholinesterase inhibitors(tacrine,donepezil,rivastigmine,metrifonate)and Ginkgo special extract EGb 761 in Alzheimers disease were compared.nMeasured on the ADAS-Cog scalenEfficacy in the delay of symptom progression or the difference in response rate between
25、active substance and placebo,showed no major differences between the four cholinesterase inhibitors and the Ginkgo special extract.nOnly tacrine exhibited a high dropout rate due to adverse drug reactions.nSecond-generation cholinesterase inhibitors(donepezil,rivastigmine,metrifonate)and Ginkgo spec
26、ial extract EGb 761 should be considered equally effective in the treatment of mild to moderate Alzheimers dementia.14The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment:new results of a randomized clinical trial.J Am Geriat Soc 2000 Level:Ib nA 24-week,rando
27、mized,double-blind,placebo-controlled,parallel-group,multicenter trial.n214 older persons with dementia(either Alzheimers dementia or vascular dementia;mild to moderate degree)or age-associated memory impairment.nEGb 761(2 tablets per day,total dosage either 240(high dose)or 160(usual dose)mg/day)or
28、 placebo(0 mg/d).nIntention-to-treat analysis showed no effect on each of the outcome measures for participants who were assigned to ginkgo(n=79)compared with placebo(n=44)for the entire 24-week period.nNo beneficial effects of a higher dose or a prolonged duration of ginkgo treatment were found.nGi
29、nkgo is not effective as a treatment for older people with mild to moderate dementia or age-associated memory impairment.15A 26-week analysis of a double-blind,placebo-controlled trial of the ginkgobiloba extract EGb 761 in dementia.Dement Geriatr Cogn Disord 2000 Level:IIa nITT analysis:after 26 we
30、eks treatment with a 120-mgdose(40 mg t.i.d.)of EGb 761(EGb).nDouble-blind,placebo-controlled,fixed dose,parallel-group,multicenter study.nMildly to severely impaired Alzheimers disease or multi-infarct dementianFrom 309 patients,244 patients(76%for placeboand 73%for EGb).nPlacebo group showed a sta
31、tistically significant worsening in all domains of assessmentnEGb was considered slightly improved on the cognitive assessment and the daily living and social behavior.nMean treatment differences favored EGb with 1.3 and 0.12 points,respectively,on the ADAS-Cog(p=0.04)and the GERRI(p=0.007).16The ph
32、armacological effects of ginkgo biloba,a plant extract,on the brain of dementia patients in comparison with tacrine.Psychopharmacol Bull 1998 Level:III nEGb or tacrine,possible or probable Alzheimers,open,uncontrolled trial n18 subjects an average age of 67.4 years with light to moderate dementia nR
33、andomly a single oral Test-Dose of either 40 mg of tacrine or240 mg of EGb2 in two separate sessions within 3-to 7-day intervals.nThe results also showed that 240mg of EGb has typical cognitive activator CEEG profiles(responders)in more subjects(8 of 18)than 40 mg tacrine(3 of 18 subjects).nBecause
34、of the small sample size,we could not test the hypothesis that subjects who showed cognitive activator-type pharmacological response to the first Test-Dose of EGb or tacrine also exhibit more therapeutic effects(compared to nonresponders)when drugs are administered chronically.17Clinical efficacy of
35、 Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type.J Psychiatr Res 1997 Level:Ib n240 mg/day of Ginkgo bilabo special extract EGb761 nDouble-blind,randomized,placebo-controlled in 20 outpatients,3 monthsnPsychometric confirmation of efficacy(SKT test)nPsychopathological(Clinica
36、l Global Impression)and dynamic functional(EEG findings)levels nEvidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system.18A placebo-controlled,double-blind,randomized trial of an extract of Ginkgo biloba for d
37、ementia.North American EGb Study Group.JAMA 1997 Level:Ib nA 52-week,randomized double-blind,placebo-controlled,parallel-group,multicenter study.nMildly to severely demented outpatients with Alzheimer disease or multi-infarct dementianEGb(120 mg/d)or placebo.nADAS-Cog,GERRI,and CGIC.n202/309 patient
38、s included in an intent-to-treat analysisnEGb group had an ADAS-Cog score 1.4 points better than the placebo group(P=.04)and a GERRI score 0.14 points better than the placebo group(P=.004).nEGb was safe and appears capable of stabilizing and in a substantial number of cases,improving the cognitive p
39、erformance and the social functioning of demented patients for 6 months to 1 year.19Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia.Pharmacopsychiatry 1996 Leve
40、l:IIa nGinkgo biloba special extract EGb 761 in outpatients with dementia of the Alzheimer type(DAT)and multi-infarct dementia(MID)nProspective,randomized,double-blind,placebo-controlled,multi-center study.n156/216 patients in the randomized24-week treatmentnDaily oral dose of 240 mg EGb761 or place
41、bo.nCGI,SKT,and NAB nThe frequency of therapy responders in the two treatment groups differed significantly in favor of EGb 761(p 50 articles identified,Only 4 studiesnAD,ginkgo extract,randomized placebo-controlled and double-blind study n212 subjects in each of the placebo and ginkgo treatment gro
42、ups.nOverall there was a significant effect size of 0.40(P.0001).nThis modest effect size translated into a 3%difference in the ADAS-Cog.nThere is a small but significant effect of 3-to 6-month treatment with 120 to 240 mg of G.biloba extract on objective measures of cognitive function in AD.n2 case reports of bleeding complications.21
