Correspondence
Correction
Treatment of Alzheimer's Disease
N Engl J Med 2000; 342:821-822March 16, 2000
- Article
To the Editor:
In their article on the treatment of Alzheimer's disease (Nov. 25 issue),1 Mayeux and Sano failed to mention AIT-082 (leteprinim potassium, Neotrofin), galantamine, or lazabemide but included such dubious treatments as Gingko biloba and acetyl-l-carnitine. Furthermore, the inclusion of metrifonate, rivastigmine, and eptastigmine, all of which are cholinesterase inhibitors not yet available in the United States, and the omission of huperzine A were puzzling indeed. Huperzine A, a Chinese herb, is a reversible cholinesterase inhibitor like tacrine and donepezil,2 but it may be more effective than either of those drugs. In fact, it may bind to cholinesterase more specifically than do conventional cholinesterase inhibitors, therefore providing an opportunity for the use of combination anticholinesterase therapy in patients with Alzheimer's disease (e.g., huperzine A in combination with tacrine or donepezil).3
3 ReferencesAlan A. Mazurek, M.D.
Mercy Medical Center, Rockville Center, NY 115701
Mayeux R ,Sano M . Treatment of Alzheimer's disease. N Engl J Med 1999;341:1670-1679
Full Text | Web of Science | Medline2
Taylor P . Development of acetylcholinesterase inhibitors in the therapy of Alzheimer's disease. Neurology 1998;51:Suppl 1:S30-S35
Web of Science | Medline3
Potential new east-west combination drug for Alzheimer's shows promise. Reuters Health Information, November 1999. (See http://internalmedicine. medscape.com/reuters/prof/1999/11/11.02/dd11029c.htm.)
To the Editor:
The review by Mayeux and Sano was a timely and interesting outline of recent progress in drug treatment of cognitive, behavioral, and psychological symptoms in patients with Alzheimer's disease. In the section on the treatment of the behavioral manifestations of Alzheimer's disease, the authors note that delusions, psychotic behavior, and agitation increase with the progression of the disease. In addition, they mention that “symptoms resolve or diminish in about 20 percent more patients treated with neuroleptic drugs such as haloperidol than among patients given placebo,” but in several clinical trials these drugs caused extrapyramidal signs and tardive dyskinesia in many patients.
On the basis of anecdotal evidence, the efficacy of atypical neuroleptic drugs was evaluated for similar indications. In a 12-week multicenter trial of fixed doses of risperidone and placebo in 625 patients with dementia, 73 percent of whom had Alzheimer's disease, risperidone decreased the symptoms of psychotic behavior and aggressiveness.1 Furthermore, in a 13-week flexible-dose trial of risperidone, haloperidol, and placebo in 344 nursing home residents with severe dementia, 75 percent of whom had Alzheimer's disease, both risperidone and haloperidol reduced the total score and the aggression subscore on the Behavior Pathology in Alzheimer's Disease Rating Scale than did placebo.2 A post hoc analysis revealed significantly more improvement in aggressive symptoms with risperidone than with haloperidol, whereas the severity of extrapyramidal symptoms was greater in the haloperidol group than in the other two groups. In contrast to haloperidol, risperidone did not have important extrapyramidal side effects and did not induce cognitive impairment.
2 ReferencesPeter Paul De Deyn, M.D., Ph.D.
University of Antwerp, 2610 Wilrijk, Belgium1
Katz IR ,Jeste DV ,Mintzer JE ,Clyde C ,Napolitano J ,Brecher M . Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. J Clin Psychiatry 1999;60:107-115
CrossRef | Web of Science | Medline2
De Deyn PP ,Rabheru K ,Rasmussen A , et al. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999;53:946-955
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. Mazurek was concerned that we did not mention several drugs, particularly huperzine A, that are being evaluated as treatments for Alzheimer's disease. We limited our discussion to “drugs given in clinical trials for at least six months,” and we are unaware of any published studies of huperzine A that meet this criterion.
We thank Dr. De Deyn for his update and regret that because of the the timing of the article by him and his colleagues we were unable to include their results.1 They found no significant reduction in the total score for the primary measure of behavior in either the risperidone group or the haloperidol group, as compared with the placebo group. A post hoc analysis did reveal a reduction of 10 to 20 percent in the rating of aggressive behavior in those who received either drug, as compared with those who received placebo. The discontinuation rate of 41 percent in the risperidone group was also higher than the rate in either the haloperidol group (29 percent) or the placebo group (35 percent). Nevertheless, these comparative studies are critical in establishing the effectiveness of current treatments for Alzheimer's disease.
On page 1673 of our article, the first sentence in the section entitled “Metrifonate” should have read, “Metrifonate (trichlorfon), an anthelmintic drug with no anticholinesterase activity, undergoes nonenzymatic hydrolysis to dichlorvos, a pseudoirreversible inhibitor of cholinesterase,” not anticholinesterase, as printed. Also on page 1673, the first sentence in the section entitled “Eptastigmine” should have read, “Eptastigmine is a carbamate derivative of physostigmine and a reversible inhibitor of cholinesterase,” not anticholinesterase, as printed.
1 ReferencesRichard Mayeux, M.D.
Mary Sano, Ph.D.
Columbia University, New York, NY 100321
De Deyn PP ,Rabheru K ,Rasmussen A , et al. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999;53:946-955
Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
Xiaoqiang Ma, Changheng Tan, Dayuan Zhu, David R. Gang, Peigen Xiao. (2007) Huperzine A from Huperzia species—An ethnopharmacolgical review. Journal of Ethnopharmacology 113:1, 15-34
CrossRef2
Roger Bullock. (2001) Drug treatment in dementia. Current Opinion in Psychiatry 14:4, 349-353
CrossRef3
Joseph S. Alpert. (2001) Differences in outcome between percutaneous coronary intervention and coronary bypass grafting. Current Cardiology Reports 3:3, 173-174
CrossRef4
(2000) Current Awareness. International Journal of Geriatric Psychiatry 15:7, 669-676
CrossRef
