Posted 23 August 2006

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Steven T. DeKosky and Bengt Winblad led this live discussion on 10 February 2004. This discussion was co-organized by the Alzheimer's Association and the Alzheimer Research Forum.

Participants: Antonio Alvarez, caregiver; Steven T. DeKosky, University of Pittsburgh School of Medicine; Mike Faux, caregiver; Dale Grillot, caregiver; Lisa Gwyther, Duke University; Kevin Foley, Hauenstein Alzheimer's Disease and Memory Disorders Program, Grand Rapids, Michigan; Bev Jones, Clinical Assoc Prof, Wake Forrest University, Geriatric Psychiatrist; Jim Kallio, caregiver; Zaven Khachaturian, June Kinoshita, Executive Editor, Alzheimer Research Forum; Pallavi Kakulavar, MD, Cleveland Clinic Foundation; John C. Morris, Washington University; Phyllis O'Hara, Alzheimer Specialist, RNC, private practice, former president of the Western Massachusetts Alzheimer's Association; Jeff Paley, MD; Susan Scruby, caregiver; Lon Schneider; Gabrielle Strobel, Managing Editor, Alzheimer Research Forum; Bengt Winblad.

Note: The transcript has been edited for clarity and accuracy.

June
Thank you all for logging on today.

Bengt Winblad
I am sad that I cannot see all of you. This is my first experience with a chat room.

Dear friends, I do think we agree that we have evidence enough to believe that treatment of the disturbances in the glutamatergic system is important in AD.

June
I'd like to pose a question to Bengt. Can you give us a general description of the type of patient whom you find tends to benefit from memantine?

Bengt Winblad
My feeling is that most of our AD patients will respond on memantine. Certainly, we have most experience with patients who are in a more advanced dementia stage. We see a rather quick response within two to three weeks, and that is very positive.

Steve DeKosky
Bengt, if you could add.... What is the most likely signal of response seen by you and your staff?

John C. Morris
Bengt, what are the responses not only that you detect, but also that the families report?

Bengt Winblad
The earliest signs are that the patients take more interest in what is around them and take part in activities they have not done before. Examples could be that severely ill patients can start to eat by themselves, which they have not done for a long time.

June
What about effects on language and other types of cognitive functioning?

Bengt Winblad
Caregivers and family members say that their wives or husbands are more interactive, want to discuss more, take more initiatives. For example, one husband who is a taxi driver told that when he came home, his wife had been out shoveling the snow away from the garage entrance, which she had not done for a long time.

Jim_Kallio
Are we assuming in this discussion that Namenda is being used in conjunction with a cholinesterase inhibitor, too?

Steve DeKosky
The experience of the nursing home study was without cholinesterase inhibitors. Bengt, I assume your comment was for memantine alone?

Bengt Winblad
Yes, I have commented only for monotherapy.

Bev Jones
I see many patients in AD special care units whose Mini-Mental State Examination (MMSE) is < 5. Recently, another physician has started several such residents on Namenda. Is it reasonable to expect a response in these severely affected patients?

Steve DeKosky
Bev, there will obviously be quite impaired people, non-mobile, perhaps with contractures, on whom determining a good response would be difficult. Much of the problem in designing these studies, and the reason that the early studies with cholinesterase inhibitors were done with mild-to-moderate patients, was because there was belief that it would be easier to show a positive effect on milder patients, and because there were no good tools to assess more severe cases for improvement or stabilization. We are now doing better in that regard.

Bengt Winblad
Bev, in our Latvian study we had a positive effect, also, on these patients. I have not initiated actual patients in nursing homes during the last year.

Bev Jones
Thanks. I realize data is limited on the most severely affected patients, but many families will be facing the question of whether to give Namenda a try.

June
Bengt, would you characterize the effects of memantine as being an overall improvement across the spectrum of symptoms, or is it more effective for certain aspects of the disease?

Bengt Winblad
June, I believe, without proof, that it has a good effect over the whole continuum.

Zaven
Bengt (Steve, Lon, and John, also), how much experience is there with this drug in the earliest stages of the disease (mild or even earlier)? Given the fact that the mode of action is through the glutamatergic system, one would expect it might be useful slowing disease progression by reducing putative calcium toxicity.

Bengt Winblad
Zaven, I agree about the possibility of disease modification. The preclinical data presented on memantine and its neuroprotective effects are really good and interesting.

I suppose we all have seen the new data on memantine with a possible effect also in mild and moderate stages of AD. Will that mean that we can treat the whole continuum of the disease?

Lon Schneider
The companies did not release any data, just their news releases. I don't think any of us have been able to evaluate the data. Lundbeck's trial was not positive.

Bengt Winblad
Lon, we all agree that our authorities will demand two pivotal studies that are positive. I have also seen a press release.

lhebert
Are the non-responders to acetylcholinesterase inhibitors in mild-to-moderate patients likely to respond to memantine?

Steve DeKosky
There are no published data on that question yet.

John C. Morris
I'm interested in what data are available to support benefits for memantine combined with cholinesterase inhibitors in patients with mild AD; does anyone know about such results?

Bengt Winblad
John, we have only 8-10 patients with combination. It seems to work well, but in two patients we have seen a confusional reaction that went away when dosage was reduced from 20 to 15 mg.

Lon Schneider
John, I think use of the term "combined with" acetylcholinesterase inhibitors is incorrect. The studies have only assessed the effect of memantine in patients who had been taking an AChEI for at least six months. This is an "add-on," not a combination.

Steve DeKosky
The Tariot et al. paper is the only published add-on study with AChE inhibitors and memantine. Other data have been reported in short communications but not yet published and peer-reviewed.

[Editor's Note: See ARF related news story.]

Lon Schneider
Steve, it is notable that in the moderate-to-severe stage, add-on patients had been on donepezil an average of 2.25 years before being randomized to memantine. They benefited from memantine, but the "placebo group"—those on donepezil alone—continued to deteriorate at a rather rapid rate, as though the donepezil was having no effect.

Bengt Winblad
I agree that it could be an effect of memantine alone in the Tariot paper.

Steve DeKosky
Well, it may be unfair to say that donepezil has no effect unless you removed it and saw a further decline.

June
Good point, Steve.

Gabrielle
Lon, do you mean to say the donepezil was no longer working in the Tariot et al. patients, and it was not really a combination therapy trial?

Lon Schneider
Gabrielle, a combination trial would randomize patients to donepezil alone, memantine alone, the combination of donepezil and memantine, and placebo.

Bengt Winblad
Good design, Lon.

June
So, Lon, do these data suggest that memantine has an effect on progression?

Lon Schneider
The studies haven't been done to assess progression. It's just that memantine has a clinical effect over six months in moderate-to-severe patients who had been on donepezil for 2.25 years.

June
Are there ongoing trials that can answer the question regarding progression?

Bengt Winblad
June, not that I know about.

Steve DeKosky
As for disease modification, that seems a plausible hypothesis. It awaits a disease modification study, of longer duration, to see if there is improvement. If you look at the article on neuroprotection in Parkinson's in JAMA last week by Schapira and Olanow, you can see what the problems are of interpreting such studies when there is also a symptomatic effect of the drug, as there clearly was with memantine. I am not aware of such a longitudinal study underway. Lon, do you know?

Lon Schneider
Steve, I am not aware of long-term trials.

June
Zaven asked about trials in mild cognitive impairment (MCI) or early AD patients. Are there any in progress?

Bengt Winblad
Zaven, I don't think they have started on MCI yet.

Jim_Kallio
We get many questions on the Alzheimer's list about memantine use with Exelon and Reminyl…. Will we see trials on those, too?

Antonio Alvarez
This question is for Dr. DeKosky or other doctors in the panel: Are there any data or do you have any opinion on the use of antiinflammatories together with memantine and acetylcholinesterase inhibitors? And specifically, do you think there will be any benefits on the use of Flurbiprofen as an antiinflammatory medicine together with memantine and an acetylcholinesterase inhibitor? My wife is in the early-mild stages of Alzheimer's.

Steve DeKosky
Antonio, the only treatment trial of use of antiinflammatories in AD (Naprosyn and ibuprofen) was not positive. There are no data yet in humans on Flurbiprofen, which people are interested in because of its potential effects on β amyloid.

Lon Schneider
The R-enantiomer of Flurbiprofen is an NSAID but doesn't inhibit COX1 or 2. It might modulate transcription pathways of NFκB, and it reduces Aβ42. Myriad Pharma is developing it, but there is no evidence that the use of antiinflammatories is helpful in people who already have AD. In fact, it appears harmful overall.

[Editor's Note: See ARF related news story].

Jeff Paley
Steve and Bengt, are you believers in the metal-chelation hypothesis and Bush/Tanzi's clioquinol study published recently in Archives of Neurology?

Bengt Winblad
Jeff, clioquinol is difficult to give; you have to add vitamins to avoid side effects.

Jeff Paley
Yes—B12 injections—but there is a second-generation compound without the optic toxicity; do you believe the data in terms of mechanism?

June
Hi, Jeff. I'd like to refer you to an ARF Live Discussion we had in January on clioquinol. I'd like to confine the discussion here to memantine. Thanks!

Bengt Winblad
I had an earlier question about experience of increasing dosage over 20 mg./day. My answer was that there is certainly some experience with memantine in trials on pain with 40 mg./day, but that there is a real risk that higher doses in dementia patients will lead to more side effects. Have you any experiences with higher doses?

June
Thanks for bringing this question up, Bengt. We posted a question before the chat from a woman whose husband seemed to benefit from a higher dose (40 mg.), but her physician doesn't want to go above 20 mg. (See Q & A)

Jeff Paley
To all, what does the 10-plus-year experience in Europe tell us about long-term use of memantine?

Bengt Winblad
Jeff, the European experience is that memantine also in the long-term studies is a safe drug and that really few interactions could be expected, and I think that was an important point in the European approval in 2002.

Kakulavar
In Europe, are they using memantine for mild Alzheimer's, and if so, do you know if it is effective?

Bengt Winblad
Kakulavar, it's only registered for more severe stages, but mainly in Germany it has been used for several years in milder stages of brain insufficiency and sold very well.

Kakulavar
You mean in Europe it is only approved for use for severe-stage Alzheimer's?

Steve DeKosky
Please remember, everyone, that when you ask whether a medicine is "effective," that the standard is a double-blind, placebo-controlled trial, not our clinical impression...and there are not a lot of those trials completed and reported.

June
Have any of you had clinical experience treating earlier-stage patients with memantine?

John C. Morris
I have no experience with memantine in early-stage patients. Moreover, I have no experience with memantine in "combination" (or as an add-on) with vitamin E, antiinflammatories, etc. I wonder if there are data from Europe, or if not data, at least clinical experience in this regard?

Bengt Winblad
John, in Europe we don't use vitamin E in dementia patients and are afraid of antiinflammatories due to the gastric problems. I'm sure, still, that Merz would have some data on combinations, but I don't know about them.

Gabrielle
Bengt, is it not also true that fewer people in Germany take cholinesterase inhibitors? Is memantine the drug of choice over there?

Bengt Winblad
Gabrielle, I think memantine, together with gingko, is having the largest market share in Germany.

Bev Jones
I'm interested in the prior European experience, too. For example, was there evidence in other uses that memantine helped moderate-to-severe disease more clearly than mild?

Kevin Foley
Steve, any trials underway looking at lower dosages or once-daily dosing, or reason beyond the Latvian study to believe that less than 20 mg. per day would be just as effective?

Steve DeKosky
Kevin, Bengt would be best to answer your question about lower dosing.

Bengt Winblad
Concerning dosage, I think that for glutamatergic drugs, in general, we believe in a U-shaped dose response curve. Still, 10 mg. gave a good effect in our nursing home study.

Jeff Paley
Is there any data from the European literature about use of the drug in severe disease?

Bev Jones
Are there any memantine data on frontotemporal Lewy body disease or Parkinson's?

Bengt Winblad
Bev, I would like to test in a trial for frontotemporal lobe dementia. I have treated three AD patients with severe frontal lobe atrophy and their reaction was rather modest or bad on the cholinergic drugs, but good on memantine, or actually, the addition of memantine.

Bev Jones
Good! It would seem the benefits would be not specific to AD.

Bengt Winblad
Bev, two European trials on vascular dementia with memantine gave very positive indications of effects (see Orgogozo et al., 2002 and Wilcock et al., 2002).

John C. Morris
Bengt, Lon, Steve, Gabrielle, Zaven, Lisa, June, et al., I must sign off now for another commitment. Thanks for hosting this Web chat!

Zaven
Good-bye, John.

Steve DeKosky
There is a great deal of work that has been done in Europe on memantine, and those studies, Bengt's nursing home study, and the two U.S. studies did indeed indicate the memantine appears low in side effects. I think that is why, even with questions about the magnitude of the effect of the medication in terms of changes in behavior or cognition, people are enthusiastic about it and want to try it immediately in milder cases and in other diseases. The clinical experiences will lead to decisions about doing the controlled trials that must be done to demonstrate clearly that it works. Again, the issue of a symptomatic effect versus a neuroprotective effect will complicate the design.

Bengt Winblad
Steve, I agree!

Dave Grillot
Dale Grillot here from Columbus, Ohio. I'm a caregiver and researching for a book on caregiving. I have read a number of reports of patients who have become violent when started on memantine. Can anyone comment?

Bengt Winblad
Dave, we haven't seen that with monotherapy. I have heard about one case on the combination.

Steve DeKosky
I think there have been some suggestions of agitation in the studies. I do not know of "violence." It is also difficult to characterize what might have led to agitation in many cases of more severe disease. But it deserves continuing monitoring in post-approval assessments of effectiveness.

Lon Schneider
Where do the reports of "violence" come from? Anybody have citations?

Bengt Winblad
Lon, I have seen confusion in two patients, but only heard about more intense psychiatric problems in one.

Dave Grillot
I have seen a number of posts on caregiving messenger boards about families that had to stop memantine because of violent behavior. Sorry, not anything published.

MikeFaux
So is there any data on how long memantine is effective, or what unexpected effects may occur upon withdrawal?

Bengt Winblad
Mike, there is no real long-term data, except that the Barry Reisberg study had an open-labeled phase IV for another 18 months, I believe (personal communication).

Bengt Winblad
Kevin, I still think that the MMSE is useful on the GP level. A moderately severe demented patient has a need for support in more complicated tasks, but manages well to live at home.

June
Bengt and Steve, I was struck by the data on adverse events (AEs). In many cases, the memantine group had fewer AEs than the placebo did, which suggests to me that these AEs are actually disease effects that memantine was ameliorating. Would you agree with this interpretation?

Bengt Winblad
June, I think the reduction in, for example, agitation is due to the patient's experience of thinking a bit more clearly; that reduces the problems in the interaction.

Debra Katt-Lloyd
Steve and Bengt, what has been the typical titration in practice? Do you find doctors giving a 5-mg. increase per week, or do they tend to spread it out over a longer period, e.g., waiting a month in between?

Steve DeKosky
The dose packs have a very slow increase up to 20 mg. Most people were starting with 10, then going to 10 bid when buying the drug from European pharmacies. In the U.S., the increase has been slower in those packs. But I did not see a problem starting with 10 and going to 10 bid a week later. I am curious about Bengt's greater experience in this regard.

Gabrielle
Debra, good question. I think for galantamine, the speed with which the doctor ramps up to the full dose affects how well the patient responds and the side effects (see recent ARF Live Discussion on cholinesterase inhibitors).

Bengt Winblad
Debra, in practice, I have seen everything going from 10 mg. and after one week directly to 20 mg. In the patients with frontal lobe engagement, we went much slower than the recommended 5-mg. increase per week.

Debra Katt-Lloyd
Thank you, both—my experience with MDs prescribing the cholinesterase inhibitors is often that they would be slow to titrate up even without side effects.

Zaven
I have to log out. Good-bye Bengt, Steve, Lon, June, and Nico!

June
Thanks for being here, Zaven! Good-bye.

Bengt Winblad
Good-bye, Zaven.

Jeff Paley
Steve and Bengt, is there a downside to adding memantine to acetylcholinesterase inhibitors for all mild-to-moderate patients, since the safety profile is so clean?

Bengt Winblad
In many of the European countries, the downside would be that there is no reimbursement, and the drugs are certainly very expensive.

Steve DeKosky
In addition to expense, we have a responsibility to figure out how to answer the questions in careful ways, such as in the incredibly difficult study Bengt did in Latvia in the nursing home. All our other speculation is just that, and AD patients are, as you know, very variable. The next data that will likely emerge will be from the completed studies of memantine in mild-to-moderate AD.

Kim
I don't understand. The package insert refers to three studies and the only one with significant results is when memantine is used in combination with donepezil. How can anyone consider using it in monotherapy?

Steve DeKosky
Kim, see Reisberg, 2003.

Lon Schneider
The package insert refers to three trials, all positive. The Latvia trial had patients with both AD and vascular dementia.

Kim
What about the Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change-plus (CIBIC-plus), and MMSE? Not significant?

Jeff Paley
How might you account for the fact that one study in mild-to-moderate was negative, but there was a recent one that was positive?

Lon Schneider
NPI was not a primary; the co-primaries included Aβ-derived diffusible ligands (ADDLs).

Bengt Winblad
Lon, a subanalysis of the Latvian study showed that memantine had as good an effect in both Alzheimer's and vascular dementia.

Lon Schneider
Yes, in fact, both the FDA's and Forest Laboratories' subanalyses showed that. I was reacting to the idea that two trials in the package insert were "negative." This is not the case.

Gabrielle
With cholinesterase inhibitors, clinical experience is exposing an interesting tension between the need to boost ACh levels in the AD brain and to lower them peripherally, for example, to treat incontinence. Anticholinergic drugs are quite commonly prescribed in geriatric care. This can be a dilemma. Do any of you see inklings of a similar mechanistic "tug-of-war" for memantine on the horizon, where you want to dampen N-methyl-d-aspartate (NMDA) receptors in AD, but might need to up them for other conditions?

Lon Schneider
Given memantine's action as an NMDA antagonist, you would expect it to reduce the various gastrointestinal symptoms due to acetylcholinesterase inhibitors.

Kevin Foley
Bengt, at what MMSE score would you recommend starting memantine? At 14?

Bengt Winblad
Kevin, I would start on patients with MMSE <15.

Bev Jones
As a clinician, I expect will be hard to tell patients and families they should wait until they hit an MMSE <15 before starting memantine....

Jim_Kallio
You're right…. Waiting for 15 will be very difficult.

Dr. Kevin Foley
So are you going to treat everyone?

Steve DeKosky
Bev, you are right; we all have that dilemma. The issue is how much data you need or trust, and what the expectations are. That is why I think doing the neuroprotection trial is important.

Bengt Winblad
Bev, we can, after the press release from Forest Laboratories, already see that clinicians are using it outside the approved indication on more mild patients.

Jim_Kallio
We have the dilemma, too, of when Blue Cross will quit paying for Aricept.

Jeff Paley
Again, Steve or Bengt, any idea why the mild-to-moderate studies were mixed—some positive and some negative?

Bengt Winblad
Steve, I am not sure a study in MCI will be done, as it is only recognized as an early Alzheimer's diagnosis, and they certainly will have the indications from mild to severe after some further studies.

Steve DeKosky
Bengt, is it likely that Merz or Forest, or both, will do a neuroprotection (long-term) trial to see if it slows progression?

Bev Jones
Gotta go; thanks, everyone. Steve, enjoyed seeing you on the PBS special.

[Editor's note: The PBS special is "The Forgetting."]

Gabrielle
On the future outlook: Investigational drugs called cognitive enhancers, or ampakines, modulate synaptic transmission via AMPA receptors, vaguely similar perhaps to the mechanism of memantine. What do you think of these? Do you foresee future use for AD from these candidates in the pipeline?

Phyllis O'Hara
Thanks for the Ampalex update. Wondered what happened to it!

Steve DeKosky
The AMPA receptor is different from the NMDA receptor, and we first need to see positive studies before deciding about any combination therapies aimed at the glutamate receptor subtypes.

Bengt Winblad
Phyllis, I am not so sure that influencing the AMPA receptor is as good an approach, possibly due to more side effects.

Gabrielle
Bengt, what sorts of side effects?

Bengt Winblad
Gabrielle, side effects more toward the psychotic domain. What is your feeling about effect in vascular dementia (VaD)?

Gabrielle
Steve, you are testing amyloid imaging with Pittsburgh compound B (PIB). Could you do a small study identifying people early and treating them with memantine versus not?

Steve DeKosky
We need to determine what the levels of amyloid are in the brains at different stages of disease, and longitudinally what the rates of increase are in relation to cognition, and then if all goes well, try to see if that intervention slows or reverses amyloid load. I do not think there is a mechanism currently wherein memantine would affect amyloid. But I am sure someone will think of one.

Gabrielle
Ha ha, Steve! Everyone's favorite thing eventually affects amyloid, does it not? Currently, everything is affecting BACE. I thought of it not directly as memantine affecting amyloid, but of presymptomatic amyloid as an early marker.

June
Is there any neuropathology data on patients who have been treated with memantine (and for that matter, AChE inhibitors) regarding effects on plaque load?

Bengt Winblad
June, I am not aware of reduction of plaques. We have run the Pittsburgh PIB ligand in 25 early-AD and 20 MCI patients, and in some of these on more occasions, so I am sure Agneta Nordberg will present these data in Philadelphia in July.

Gabrielle
All, we have extensive coverage of the published study by Bengt, Bill Klunk with numerous comments by other scientists, on the Alzforum news section (see ARF related news story).

June
Thanks, Bengt.

Bengt Winblad
Steve, in the ECNP meeting there were data presented both on an effect on β-amyloid production and also on diminishing the phosphorylation of tau in a report from Khalid Iqbal.

Steve DeKosky
Aha! See? It happened already. Very interesting.

June
Bengt, were you addressing your vascular dementia question to anyone in particular?

Bengt Winblad
June, I am happy if anyone will answer if we should do more trials with memantine in vascular dementia.

Lon Schneider
You should distinguish ischemic disease and continue trials in that. That's where the evidence is in Wilcock and Orgogozo's memantine trials.

Bengt Winblad
Lon, yes, perhaps "vascular dementia" is too broad and heterogeneous.

June
So what would be the inclusion criteria for a vascular dementia trial?

Bengt Winblad
June, probably we have to pick out, as Lon said, a group of patients that on imaging shows a more pronounced subcortical damage indicating that the blood-brain barrier of the penetrating vessels is not intact.

Steve DeKosky
I agree that the cases to focus on may be the subcortical ischemia/lacunar infarction cases...also easier to track longitudinally, I believe.

Phyllis O'Hara
Thanks for letting this 75-year-old nurse eavesdrop on your fascinating discussion. Later!

Antonio Alvarez
Thank you very much to Dr. DeKosky and other doctors for participating. I have to go now.

June
Thanks, Antonio. Good luck.

Jim_Kallio
Yes...what about using memantine in combination with Exelon or Reminyl?

Steve DeKosky
I suspect the companies are doing those. I do not have a lot of experience with the combination with Exelon; I have a few patients on Reminyl and memantine without problems. But we do very much need a larger experience with these to know that they are okay to use together.

Jim_Kallio
How about efficacy, too, on the Exelon and Reminyl used with memantine?

Bengt Winblad
Jim, a large study is ongoing in Germany with a combination with Reminyl. I do think we will see similar effects as with Aricept. I am not sure about the design; perhaps Lon has an idea about that?

Steve DeKosky
There are no data on efficacy. By that, I mean the type that might emerge from a controlled trial.

June
Yes, efficacy data are difficult to obtain. In the meantime, people must also worry about potential adverse effects from combining two approved therapies.

Jim_Kallio
So do we even know yet about synergistic effects of adding the cholinesterase inhibitor with memantine?

Steve DeKosky
I think there are many cases in which people have done that—added memantine to ongoing donepezil or galantamine. The former case would be like the Tariot study. I do not know if you can get an answer about "synergy" from that. Combined effects may depend on the stage at which you initiate the therapies.

Jim_Kallio
A lot of caregiver concern is about whether it's worth the money to add memantine therapy…. It can be expensive without insurance.

Lon Schneider
Again, no evidence that memantine and donepezil together provide additive effects, but strong evidence that memantine provides effects in people who had been taking donepezil for an average of two years or so.

Dave Grillot
I think the big questions for families are: When should it be started and when is it no longer worthwhile, and apparently, should the person stay on cholinesterase inhibitors?

Steve DeKosky
Dave, specific data on which to make recommendations about your important questions are not available yet. No one knows when to take off the cholinesterase inhibitors. And although we know that the studies show effects of memantine on AD subjects with MMSE of 15 and below, we don't know "how high" to go—or won't with certainty until the mild-to-moderate AD studies are completed and reported, which we hope will be soon. The answer to when to stop is not a simple or unitary one, and requires careful discussion with your doctor and consideration of the status of the patient.

June
If a patient is already on, say, donepezil or Reminyl, can a physician feel comfortable about adding memantine to the treatment, in terms of potential adverse effects?

Lon Schneider
The evidence, as thin as it is, is that memantine added to donepezil reduces adverse effects, that it doesn't add AEs.

June
Lon, that's good to know. Based on what we know about the mechanism of memantine, are there any classes of drugs, foods, etc., that people should not combine with memantine?

Bengt Winblad
June, there are really few precautions to be taken, but certainly we have to be more careful with patients with reduced kidney function, recent heart infarction and, according to the recommendations, it should not be used in patients with epilepsy.

Susan Scruby
For what it's worth, my mother has been on Aricept for some time, though at a low dosage. She seems unable to tolerate the higher dosage (we've tried three times). She started on the titration pack of Namenda on January. 31—it may just be wishful thinking on my part, but she does seem to be more engaged. Many of her conversations don't make sense, but she is more alert and aware, and more interested in talking with people and participating. This may pass, too, but I'll take what I can get.

Steve DeKosky
Susan, so will we. Amen!

Bengt Winblad
Susan, I think what you report is exactly what caregivers report for us in Stockholm.

June
Sadly, our time is up. I want to thank our guests for participating in today's chat, and our audience for being here.

MikeFaux
Thanks, Bengt, Steve, Lon, June, et al. for all your work!

Steve DeKosky
June, I'm pleased by the thoughtful questions and concern of both the clinicians and caregivers in this session, and for Bengt to do this. Many thanks.

lisagwyther
This has been interesting.

June
You may also send questions by e-mail: junekino@alzforum.org. Thank you, Bengt, Steve, and all! I have to say farewell. Bye!