Dr. Joshua Uy is a geriatrician who is interested in taking his "experience as a solo practitioner in Shickshinny, PA and my academic training as a family physician and geriatrician and make it accessible to virtually anyone."
He writes an informative blog that touches on a variety of subjects that would be of interest to us as caregivers. The most recent is on the effectiveness of Aricept and Namenda.
Here is the link: http://thegeriatrician.blogspot.com/2011/05/does-aricept-work-yesnomaybe-so.html
I have put a link to his blog up on my home page - www.thealzheimerspouse.com - on the left side under "Other Links" .
I am currently discussing with Dr. Josh the possibility of him becoming a regular contributor to my website.
This picture is from Mass General's decades long database of patient info. The top picture is the placebo group, the middle one is Aricept only and the last one is Aricept plus Namenda. What is being measured is cognition (Blessed Dementia Scale) where the higher the number the greater the impairment. The dark line going across each graph is the line of best fit or approximately the average of each group. The flatter the line, the more preserved the cognitive ability. Each little line with dots is an individual person.
The punch line from the study is that this is the longest cohort controlled data published to date (2008) and not only does it confirm a benefit to medications, but an increasing benefit over time. Let's look at this....
So does Aricept and Namenda work?
1. Yes: In this study you can see that the dark line in the bottom picture (Aricept+Namenda) is flatter than the dark line in the top picture (Placebo). This is consistent with almost every placebo controlled study. By the time you get to the end of the study, the group on treatment has an overall/average score that is better than the placebo group.
2. No (You'd never know part 1): If every patient achieved that average score for the population, you would likely never know the difference. If one person worsened by 6 points (out of 36) on placebo but another person worsened by 4 points, you'd be hard pressed to figure out who kept two of their points. While these results are statistically significant, clinically, very difficult to tell. This picture is also seen when looking at function (Activities of daily living) or any other measure of Alzheimer's. Average benefit is incredibly difficult to tell without looking through the magnifying glass of a researcher.
2. No (You'd never know part 2): But every patient does not achieve the average benefit. That should be clear from the chaos of the light lines connected by dots. There is an incredible variation of the course of dementia whether on treatment or off treatment. Patients improve, stabilize and decline whether they are on treatment or not. Trying to compare how a patient is doing compared on treatment to guessing how they would have done off off treatment to measure effectiveness for an individual patient is futile because you just never know. Regardless of group, you can see in this picture that for any specific individual patient, you can see a matching patient in another group. In other words, a stabilization of MMSE, a decline of only 1 point per year, an improvement of 1 point per year, an improvement in ADL's can all come out of any group.
3. Maybe so: So does it work? The answer is maybe. But you'd never know. It is clear these drugs have an effect in populations, that the response is incredibly variable. They may really work. For a very small proportion, they may work really really well and those improvements may be masked in groups of people. But it should be clear that the average person benefits little or not at all. So why do most people feel that these drugs do nothing? An incredibly variable response which is very very small leaves a lot of us thinking that these medications don't seem to be doing anything most of the time. It's just so hard to tell.
Conclusion Would I take it if I started with mild dementia? Yes, if I were healthy, were on minimal medications, did not have to sacrifice anything to afford it and most importantly had zero side effects from the meds. Also, I'd want to have a decent quality of life (personally meaning that I could communicate and not be in a lot of pain)
Second conclusion: Be very wary of any treatment of dementia that says it works and publishes their average data between two groups of people. The skeptic in me would want to ask: 1. how would I know if it is working so I can stop it if it is not working? 2. What is the exact benefit and what proportion of people achieve that benefit.
Thanks for posting this information. My husband has been on Aricept for over ten years and Namenda for about three years. He is declining further into stage six to the point where he needs help with ADLs. I have been trying to decide on whether or not to continue these medications—they are very expensive. Since all of the studies I had seen were terminated after several years, I assumed that there probably was not much long term benefit. Your charts show that “yes”/”maybe”, there may be some benefit yet. So now what do I do?—I still don’t know. I wish someone else could make the decision for me.
I recall laughing when I read the accompanying literature for one of these years ago. Said something along the lines of: "You can tell _____ is working if you see an improvement, a worsening, or no change." Pretty much covers it all, no?
I personally kept Lynn on them until he reached the later stages. I didn't feel it was prolonging the inevitable. I hoped more that they would prolong the time between middle and late stage. Though I knew it was of course not a cure, there was a chance it could help keep him more "with it" longer. That was important to me. If it helped I honestly do not know.....but I felt I had to try.
I think this is a tough decision. Talking to the dementia researchers at the Penn Memory Center (NIH funded similar to Mass General's center), the drop off from stopping meds is overblown. If the medications do little to begin with, there's little reason to think that stopping them will cause a harm to the patient. I did see one study where stopping the med for 3 weeks, seeing if there was a decline, then restarting it actually would help a patient get back to their previous improved level whereas waiting 6 week may see a permanent decline. Based of this one study alone, I do bring patients back 3 weeks after stopping these meds just to check in.
(https://files.me.com/joshandsusie/er0k9l)
No they don't cure alzheimer's or even halt the progression. In all treatment arms (placebo, aricept, combo), there is a progression of disease. Certainly there has never been any researched mortality benefit. It seems there is increasing benefit over time for a small proportion of people.
If there seems to be no benefit, I would consider a 3 week trial off the med.
If disease has progressed where the patient has a poor quality of life (however that is defined), I would also strongly consider stopping it.
If there are side effects, stop it for some time
If it means paying the bills vs meds, stop the meds too.
If there are no side effects, it is easily affordable and the person seems to be feeling good, even if it may not be doing a lot, I would leave it alone for now.
thanks Joshua. My husband has been on galantamine since 10/08. Have not read many studies on it. He tried Namenda but the side effects were too much and he wanted to stop it. He seems to be holding steady on cognition although his short term memory is shot. He has surprised though with the new memories he makes. We are traveling in our RV staying in places a month or two then moving. He was learning the way back to the park by the time we left. We are now in a park where I am working until October. He is remembering the people I work with and those who are long term in the park. I think the traveling has been a positive for him vs just sitting in one place with no interaction with others. The sunshine all the time has not hurt either.
His sister on the other hand has had a slow, steady decline - really no stablizing at one place. His dad died last year after a 25 year battle. His eyes and brain were donated there in Boston - would be interesting to know if they discovered anything like why did he hand on so long, etc. He was on no medication for AD until my MIL died in 2001 and he went into the VA home - then they put him on Namenda.
Thanks, Joshua, for your helpful information. I have another question. Several years ago there was some discussion about huperzine A as a substitute for Aricept. If I discontinue Aricept I have considered using it. Have you had experience using huperzine A and what is your opinion about it? This is the information posted by Sunshyne in Noverber of 2008:
"Lori, huperzine A and aricept are both cholinesterase inhibitors, so the basic function is the same. They do have somewhat different biological activity profiles, however. And huperzine A is clearly much more powerful, since the effective dose is so much lower.
"You would not want to give huperzine A to a healthy person on a regular basis, any more than you would want to give a healthy person Aricept. But a patient whose brain is having problems with the cholinergic system, these meds can be very helpful.
"There has been a very large scale, two-and-a-half year, clinical trial on huperzine A, which finished up just a few months ago. For the first six months, participants were given either placebo, 200mcg twice a day, or 400mcg twice a day. After that, the trial went into an open-label stage, in which all participants received the med for two years. My husband was on the lower dose (200mcg twice a day), for the entire time.
"Huperzine A was found to be very well-tolerated, and safe, at the higher dose. That was also the only dose that was shown to be effective during the first six months of the trial. The lower dose showed a trend toward efficacy, but it wasn't statistically significant. (I haven't been able to find the results from the entire 2.5 years published anywhere yet.) My husband very clearly benefited from the med. I'm keeping him at the lower dose until he starts to slide, and will then increase it to 400mcg 2x day.
"And yes, at $10 per month, there would be quite a cost savings!"
Hi Lori, I wish I knew more about Huperzine A but I don't. I hate to say, but I tend to be skeptical of pharmacological treatments in general because as a clinician, I care a little bit about populations but I really care about the person sitting in front of me and most research is very very hard to apply clinically. What I would want to see from any treatment (whether it is a medication, supplement, word puzzles or anything else) is what the average benefit is between treatment and placebo, justification that the difference is clinically meaningful not just statistically meaningful, what proportion of the patients achieve that clinically meaningful threshold, defined criteria for response and a safe way to know when a medication can be discontinued. Without that context, too many people are going to start meds, wonder if they are working, continue them due to fears that maybe they are working, tolerate side effects and costs when nothing is really being achieved. Or on the flip side, people will stop meds when they are actually making a big difference that is not easily observable.
From the Penn Memory Center, there isn't as much research with cholinesterase inhibitors as there is now with targeting abnormal proteins in the brain. A friend who researches dementia, is looking at targeting blood flow in the 40's and 50's through use of statins. It may work, it may work as well as aricept/razadyne/exelon but that isn't saying much.
The definitive guideline by the ACP/AAFP can be found here (http://www.annals.org/content/148/5/370.full.pdf+html) with a summary here (http://www.annals.org/content/148/5/I-41.full.pdf+html) and the very detailed evidence summary here (http://www.annals.org/content/148/5/379.full.pdf+html). NIH's most recent summary can be found here (http://consensus.nih.gov/2010/docs/alz/ALZ_Final_Statement.pdf). It tends to be a little pessimistic.
Dr Josh- We are very fortunate to have you on board this site, and I am very grateful to see that there are doctors out there with common sense. I too have done the same clinical studies, not only with my laboratory rats, but also with patients of all ages. My studies using Jelly beans as a cure and also as a placebo, seemed to provide me with the same statistics as the medical studies, and my graphs look identical as the clinical studies. I have read your blogs, and find that you are indeed a rare doctor, who considers the individuality of a patient. Thank you for being part of our team of experts. Also, you may bill me for any advice you give, and I will immediately fax you cash.....:}... You are like a breath of fresh air to me, and your blog just reaffirmed what I originally had figured out by myself, except that I won't be financially burdened by the bills./.. phranque
Amen Phranque. I too am so happy to have Dr Josh. So many doctors seem to be detached from the patient and family. I want a doctor that CARES! that LISTENS to the caregiver. We know our spouses better than anyone. Welcome to our little corner of the medical world Dr Josh.
I was so impressed that Dr. Josh not only reads and posts here, but uses these boards as a educational tool for other doctors. I'm sure they will learn as much here as all of us spouses have.
Dr. Josh, You sound like a busy man & for you to take time out of your schedule to help us here, well we all appreciate it. I also appreciate the fact that a lot of times you don’t wait for us to ask a question, you just comment on what we write & it answers our question before we have to ask. Thank you for being such a caring doctor & person!
Thanks for being here, Dr. Josh. I'm sure we will all learn from you and I appreciate your time and help. My husband was on Aricept for many years (couldn't tolerate Namenda) but when he reached the point he could no longer walk, feed himself, carry on a conversations, etc., I talked to his neurologist and we decided together that it was time to drop the Aricept.
Mom has been on Namemda for 3 years. Have tried Aricept 2 times but the dreams are too disturbing for her. So it has been just Namemda. We just took her off. We looked at the side effects of most of her meds and saw how many effect sleep, appetite, and cause tiredness, all problems with her. We just upped her depression med and seems less sad but now so quiet and still so tired. Hope to see some improvement on the tiredness, without the Namemda. May even back down again on the depression med. Makes me so sad, I feel like we are just experimenting with her life, even though, everything we do is for her best quality of life. We are also trying the coconut oil. No improvements yet. Just needed to vent today. I thank God for this site. It has given me so much information on A. Bopeep3
Hi Bopeep3 As a clinician, I wish there were a way to make the decision easier for patients and families. I wish we had a way to know which medications are going to work, if they're working, what will happen if we stop them. The medications are trial and error and even then you never know if they are working for sure. But the positive that I take away is that the most important thing for patients with alzheimer's is not medications but the care they receive: nutrition, comfortable environment, physical activity, social interaction and touch, conversation. In some ways I feel it's good that the answer isn't a pill but is found in people. It does put some more burden on caregivers to hear that, but more hope too because we can't come up with new medications on our own, but we certainly can think of creative ways to care for people. Without any question, you are doing more for your mother than any medication on the market today, even if you feel you are not doing enough, it is much more important, and meaningful than what medications can do. If I could make caregivers look at the positives of what they are doing for their loved ones instead of what they wish they could do, I think more caregivers would be able to have immense satisfaction at the heroic things they do instead of feeling overwhelmed. It's easier for me to see sometimes because I see patients who do not have families who care (or who do not have families at all) and their is such a difference in outcomes. I'm sure you're doing a great job and your mother is blessed to have you. josh
Hi Bopeep3 As a clinician, I wish there were a way to make the decision easier for patients and families. I wish we had a way to know which medications are going to work, if they're working, what will happen if we stop them. The medications are trial and error and even then you never know if they are working for sure. But the positive that I take away is that the most important thing for patients with alzheimer's is not medications but the care they receive: nutrition, comfortable environment, physical activity, social interaction and touch, conversation. In some ways I feel it's good that the answer isn't a pill but is found in people. It does put some more burden on caregivers to hear that, but more hope too because we can't come up with new medications on our own, but we certainly can think of creative ways to care for people. Without any question, you are doing more for your mother than any medication on the market today, even if you feel you are not doing enough, it is much more important, and meaningful than what medications can do. If I could make caregivers look at the positives of what they are doing for their loved ones instead of what they wish they could do, I think more caregivers would be able to have immense satisfaction at the heroic things they do instead of feeling overwhelmed. It's easier for me to see sometimes because I see patients who do not have families who care (or who do not have families at all) and their is such a difference in outcomes. I'm sure you're doing a great job and your mother is blessed to have you. josh
my dh was on Aricept for about 6 mos., then Namenda was added. DH decided he wasn't taking the meds anymore because he didn't like the side effects. Dr. then put him on the Excelon patch which he tolerated very well but dh said it wasn't helping so he stopped that. I did not notice any difference. Dr. said if I didn't notice anything then they were not helping. That was six months ago. I have not noticed any appreciable downhill slide. His AD is very slow-pregressing.
My DH started on Namenda 5mg 2xday in January 2009. Then it went to 10mg 2xday. Then Aricept was added. Attempts were made at Depalote (horsepills), Depakote (sprinkles), and Keppra. The only sleeping pill he has ever been on has been Trazadone - starting with 50mg and now up to 100mg. The Aricept was stopped after his first seizure. The Depakote and Keppra turned him into a slack jawed slobbering zombie so I stopped those. He is still on the Namenda and I started durabinol 2.5mg yesterday. Durabinol is the generic for Marinol, the marijuana pill. Call me crazy, but it is the first night in a year he hasn't paced, been restless, stood in front of the TV so no one could see and ate like a horse! At bedtime he was able to get one leg out of his jeans on his own. I can't even remember the last time he was able to take anything off when he was supposed to. He crawled into bed properly, not across it or diagonally. I can't tell you the times I've been left to sleep in a corner or with my own feet hanging off the bed because of how he's positioned himself. No, I can't sleep in another room because his worst times are at night so I need to be there. It's like when you bring the new baby home and try putting him in another room and he sleeps through the night. You are up all night checking on him. My last hope is for this marijuana pill. I've tried everything else! That includes hyperzine, gingko, vitamin C, maitake mushrooms...you name it! I remember reading that vitamin C deficiency could cause the same symptoms as AD. Boy, was I on cloud 9. Oops, vitamin c deficiency was not the problem. Damn, he really does have AD.