Parminder Raina, PhD; Pasqualina Santaguida, PhD; Afisi Ismaila, MSc; Christopher Patterson, MD; David Cowan, MD; Mitchell Levine, MD; Lynda Booker, BSc; and Mark Oremus, PhD
4 March 2008 | Volume 148 Issue 5 | Pages 379-397
Purpose: To review the evidence for the effectiveness of cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and the neuropeptide-modifying agent memantine in achieving clinically relevant improvements, primarily in cognition, global function, behavior, and quality of life, for patients with dementia.
Data Sources: Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE, EMBASE, Allied and Complementary Medicine Database, CINAHL, AgeLine, and PsycINFO from January 1986 through November 2006.
Study Selection: English-language randomized, controlled trials were included in the review if they evaluated pharmacologic agents for adults with a diagnosis of dementia, did not use a crossover design, and had a quality score of at least 3 on the Jadad scale.
Data Extraction: Data were extracted on study characteristics and outcomes, including adverse events. Effect sizes were calculated and data were combined when appropriate.
Data Synthesis: 96 publications representing 59 unique studies were eligible for this review. Both cholinesterase inhibitors and memantine had consistent effects in the domains of cognition and global assessment, but summary estimates showed small effect sizes. Outcomes in the domains of behavior and quality of life were evaluated less frequently and showed less consistent effects. Most studies were of short duration (6 months), which limited their ability to detect delay in onset or progression of dementia. Three studies directly compared different cholinesterase inhibitors and found no differences in cognition and behavior.
Limitations: Limitations of available studies included short duration, inclusion of only patients with mild to moderate Alzheimer disease, poor reporting of adverse events, lack of clear definitions for statistical significance, limited evaluation of behavior and quality-of-life outcomes, and limited direct comparison of different treatments.
Conclusions: Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia.
http://www.annals.org/cgi/content/full/148/5/379
Placebo pills for sure.
Definitely not for MCI
They might work .. but doesn't keep you out of a nursing home.
DrMurdoch:Placebo pills for sure.
I'm afraid that I agree. A terrible disease, and "Something has to be done", I suppose.
THESE MEDS COULD BE OFF THE MARKET, and the hardship caused by their cessation would be minimal. There is little return on their use, I'm afraid. Anti depressants work better for dementia, in general, than do these meds.
I am resentful that there is movement afoot to discourage the use of major tranquilizers (SEROQUEL, RISPERDAL, ZYPREXA) in these patients. These meds are expensive, but they will keep the caretaker sane, and keep the demented from hurting themselves or others. I trully believe the effort to discourage the use of these meds is strictly about the cost.
I may need to search again but sometime during my fellowship in Geriatrics between 1992 and 1994 2 opposing articles, Lancet and NEJM with accompanying editorial suggested to search beyond anticholinesterase medications. probably the premise was the toxic drug Tacrine requiring higher doses to prove some benefit.
Somewhere along the way the newer generation anticholinesterase were developed and more tolerated. Personally it truly seems helpful in mild disease and slows the progress based on MMSE. I questioned its marketing to moderate to severe but it seems to control behavioral issues as well. Regarding the neuropeptide, NMDA inhibitor, I observed improvement in language.
In the end, the treatment utilizing these drugs, should be discussed on an individual basis, just like any other conditions, rather than the herd concept.
I feel that the treatment of this devastating illness, should go past the anticholinesterase and look further into inflammation and microvascular injury causing the Beta Amyloid findings in plaques. I suppose with the current upcoming molecular and pharmacogenomics we will soon find out better treatment of this condition. Meanwhile we should truly modify our lifestyle and continue stimulating our brain.
Interesting links:
http://www.medscape.com/viewarticle/568585_3
http://www.medscape.com/viewarticle/565871
Rheumdoc, you mean Psychotropics. Theuse of psychotropics I do not believe is discouraged, unless we are dealing with Delirium, which Demented patients are prone to. The reference to Dementia, in this discussion is referring to AD. Last time I verified there are 60 dementing conditions and we will be 80% correct if we label it as AD and Multi infarct dementia as our top 2 diagnosis. The second common type is lewy body dementia, this one is a pain to manage if unrecognized.
The most recent controversy with anti-psychotics is that they reduce life expectancy.
DrMurdoch: The most recent controversy with anti-psychotics is that they reduce life expectancy.
And my response is that in a person with little or no quality of life, and agitated to the point that the family wants to, or has to, institutionalize them, there seems to be little point in worrying about shortening life expectancy.
In fact, isn't it well known that we don't worry about "life expectancy" when giving morphine to a dying patient to palliate them?
And in so many demented patients the use of benzodiazepines just seem to help temporarily, but lead to a cascade of worsening confusion that is "counter" palliative. I doubt I am the only one to witness this phenomenon.
These psychotropic meds, as Roger calls them (I think that name is too general, so I am call them major tranquilizers) are useful as palliation, and once they're being used that way, it seems silly to assess life expectancy. The study by the US govt. was so, as my teenage daughter would say, "random" in it's conclusion that the drugs should be used in these diseases as a last resort, or NOT AT ALL in dementia patients.
That conclusion smacked of Wall Street-like FUD by a govt attempting to save money. Many of these patients are already institutionalized, and the meds are given there, at the gov't's expense. I cannot rationalize any other reason for their conclusions.
Incidentally, I often use these same meds at the end of life for other diagnoses, when the suffering by the patient is so great that they are literally panicked by imminent suffering and death. These meds really palliate, then, because too often the complaint by the patient is of pain, and they will be given narcotics in high enough doses that they become semi comatose. Instead, sometimes the patient is asking for help, but it's for their anxiety. Sometimes generic alprazolam is not the right answer in these dying patients, but something to curb their fear, (and not surprisingly, curbing the fear, allowing sleep often helps decrease their perception of pain). At the same time, these patients are often left alert by these meds, without changes in their personality, and will be able to interact with their families at a much higher cognitive level. Both the patient and the family appreciate this.
I AM NOT saying that dying people are crazy, only that they can be so emotionally charged that they stop making sense, or are living in a perpetual panic attack.
Now, I am giving opinion, as to the usefulness of these drugs. However using these meds as palliation is OFF LABEL use, and eventually, it seems, that is going to be against the law in the U.S.of A., the way things are going now.
There's just not enough money to go around, I'm afraid, and it's leading to this foolishness.
Indeed foolish not to use psychotropics. The use of drug always has its risk and benefit. A confused agitated patient is at risk of hurting others and him/herself. In moderate to advance dementia, quality of life is gravely affected to these individuals and certainly the care givers. The benefit of non sedating psychotropics indeed are beneficial in such cases.
Anyone have the link to the study? I have a gut feeling that these studies are not exclusively done on Moderate to severe demented patients with psychotic features. One wonders of lead time bias in these studies.
I'm with you, I use them all the time.
I very often use the older anti-psychotic medications.
The reduced Parkisonism of the newer generation is over stated.
DrMurdoch:The reduced Parkisonism of the newer generation is over stated
I have caused EPS with low dose Abilify, twice now. I will NOT use this drug again. I've seen it with Risperdal, as well. Never with Seroquel or Zyprexa, though it's known to happen. For short term use, as for palliation, I think using the older drugs is preferable. But for long term use the newer meds are better, and as you know I use them for Bipolar disease and Fibromyalgia if the mood stabilizing anti seizure drugs don't work, or if someone is so frantic that I need to bring them down NOW. The safer ones cause weight gain hand over fist, so they're not THAT safe. But there was a time you could tell any schizophrenic on the street due to their EPS, and that is no longer the case with the new ones.
One could argue that society would LIKE having EPS, like a scarlet letter, to announce the diagnosis. But I wouldn't.
Aripiprazole, is a newer antipsychotic, and there are so many good options out there it makes it impossible for me to dream up a scenario to use this drug. It will likely fall under my 3-7 year rule:
If it is a novel drug, I try to wait three years to prescribe it, any bad reports, I wait longer. If I have a patient whom has exhausted all current options and I feel might benefit from this .. I will prescribe it.
Aripiprazole isn't exactly a "me, too" drug, as it appears to work differently that other atypicals, this brings the possibility of unique benefit / unique risk.
ZIPRASIDONE is a new atypical antipsychotic in Canada, it's definitely a"me, too" drug. I'll probably wait 5 years or longer to prescribe it. I still like olanzapine for short term use. But should be monitored for weight gain.
Re: donepezil and Alzheimer's disease.
Benefits of treatment were also seen on measures of activities of daily living andbehaviour, but not on the quality of life score. The benefits are small, but for peoplewith Alzheimer’s disease they can often be important.
cochrane.org article