'Strongest Evidence Yet' Links Anticholinergic Drugs, Dementia

[Stavia]

Julie, agreed re medications, only if absolutely necessary and IMO that applies to everyone, regardless of apoe status.
I'm kinda worried about supplements as well. I know I'm sweepingly generalising but there is lack of long term data for most of them....(I'm not knocking anyone's favourite supplement in particular, just musing)

[pgf54]

I think time will prove you soooooo right Stavia with regard to supplements.............Paul

[rep]

SandraZ said

So they divide the drugs up as a risk 1 (lowest) 3 (highest risk) with the caveat from the article and Merlou that even low doses or low risk taken regulularly becomes a high risk!,

So does that mean that having taken Prozac (fluoxetine), which is Risk 1, for almost 20 years places me at high risk?

I just went off it last month and I'm taking SAM-E instead. Anyone know if SAM-E is risky?

How about L-Tyrosine?

[rep]

Would somebody please provide the exact text from the article that states the part about low risk ones taken regularly becoming a high risk? Thank you.

even low doses or low risk taken regulularly becomes a high risk!

[MarcR]

Would somebody please provide the exact text from the article that states the part about low risk ones taken regularly becoming a high risk? Thank you.

even low doses or low risk taken regulularly becomes a high risk!

Good catch, rep - I think the Medscape article summarizing the new paper said that low doses of any anticholinergic drug taken regularly can put one at high risk for dementia. That article did not address the issue of varied degrees of anticholinergic effect - risk - among the drugs. Perhaps the actual published paper normalizes those variances using a burden assessment schedule, but the Medscape summary does not say one way or the other.

[Stavia]

Rep, some studies show that certain antidepressants may be protective against dementia. Yours is in this class, the SSRIs.
It's not as simple as just looking at the anticholinergic effect and thinking in black and white terms. Drugs usually have multiple effects in the human body which is very complex. (I know, I'm beating my big picture drum again lol but just looking at the anticholinergic effect of a medication IMO is too reductionist and can lead people to making decisions based on an incomplete picture)

Bottom line honey is that not treating a depression is a risk for AD. Fluoxetine IMO is a lower risk than being depressed.
Sam-e has not had long term testing in anyone let alone e4s. Just because its a supplement doesn't mean its guaranteed to be safe. Again, not criticising anyone's choice, I just don't want anyone to be mislead into black-white thinking and the trap of drug=bad vs supplement=good

Sorry I can't give you certainty but what I do know is valid for us is that depression untreated is not good. But there are other ways of managing mood other than medication/supplements which I know Richard is an expert in such as excercise, CBT, mindfulness meditation, sleep etc.

[RichardS]

Just to put some things in perspective:
From the World Health Organization a discussion about total disability adjusted life years (DALY):
http://www.google.com/url?sa=t&rct=j&q= ... 7526,d.aWw

Unipolar depression makes a large contribution
to the burden of disease, being at third place worldwide
and eighth place in low-income countries, but
at first place in middle- and high-income countries.
Effective treatments for depression are available,
suggesting that this burden could be reduced.

The global disease burden of depression (99 million lives in 2004) easily exceeds that of heart disease (23million), dementia (15million), and cerebrovascular disease (13 million) put together. Treat your depression like your life depends on it...because it does.

For non-pharmacological treatment of depression and other mental health conditions, a good place to start with a fairly readable scientific article by Dr. Roger Walsh is here: https://www.google.com/url?sa=t&rct=j&q ... Ww&cad=rja

[rep]

I have switched from Prozac to SAMe for a couple reasons. One is that Prozac ceased being very effective for me.
The second reason is that I unfortunately have a rare genoset called GS224 http://www.snpedia.com/index.php/Gs224
Among other things it says

You have two copies of a GCH1 variant associated with lower levels of tetrahydrobiopterin (BH4) and total biopterins. BH4 is used in the production of several neurotransmitters, including serotonin and dopamine. While many people carry this with no obvious ill effects, it does seem noteworthy.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699614/ reports median plasma BH4 levels in patients with this genotype were reduced by approximately 80%. Several potentially serious health issues could result from an 80% reduction in BH4 levels.
There may not be enough BH4 to convert phenylalanine to tyrosine. Therefore, phenylalanine can build up in body tissue and cause health issues (like high blood pressure).
But, now there may not be enough tyrosine, which is needed to create dopamine. And so then there may not be enough dopamine, which can possibly lead to symptoms SIMILAR to conditions like Fibromyalgia and Parkinson’s (but not actually Parkinson’s).

Here is a web page on BH4, or tetrahydrobiopterin http://en.wikipedia.org/wiki/Tetrahydrobiopterin

Nice to finally discover my genetics since I have a history of depression and fibromyalgia. I have started taking methyl B12 and methylfolate (the methylfolate alone can help with depression, I've discovered) but SAMe can supposedly help increase BH4 as well.
http://www.cnsspectrums.com/aspx/articl ... cleid=1267 The article is from a Dr. Stahl, PhD and MD Dr. Stahl is adjunct professor of psychiatry in the Department of Psychiatry at the University of California-San Diego in La Jolla.

Both MTHF and SAMe may therefore impact the regulation of various critical components of monoamine neurotransmitter activity not only by indirect modulation of neurotransmitter synthesis by promoting the synthesis of BH4 enzymatic cofactor, but also by modulating catabolic enzymes, monoamine transporters, and neurotransmitter receptors via methylation and its downstream effects (Figure 5).60-65

I like this since it seems to strike at the heart of my problem. It does seem to be helping me.

Furthermore, this fairly recent study seems to validate SAMe as being effective. I do agree we don't know the long term effects but I think the same can be said of fluoxetine.
http://www.jad-journal.com/article/S016 ... 9/abstract

Results
On the primary outcome of the Hamilton Depression Rating Scale (HAMD-17), a significant difference in improvement was observed between groups from baseline to week 12 (p=0.039). The effect size from baseline to endpoint was moderate to large for SAMe versus placebo (d=0.74). SAMe was superior to placebo from week 1, and to escitalopram during weeks 2, 4, and 6. No significant effect was found between escitalopram and placebo or SAMe. Response rates (HAMD-17≥50% reduction) at endpoint were 45%, 31%, and 26% for SAMe, escitalopram, and placebo, respectively; while remission rates (HAM-D≤7) were 34% for SAMe (p=0.003), 23% for escitalopram (p=0.023), and 6% for placebo. No correlation between baseline histamine level and reduction of HAMD-17 score was found for either the SAMe or escitalopram groups. Baseline carnitine levels were also not found to moderate response to either treatment.

If anyone knows of other ways to increase BH4 (Tetrahydrobiopterin) please post. It seems critical to my health to find ways to have enough of it.

[circular]

Checking in briefly after being away for a while and glad to see this topic getting more press. I've never been able to tolerate anticholinergics. Even Zyrtec (2nd gen) sedates me. Maybe my BBB is particularly leaky The second gen antihistamines are not anticholinergic free, just a lot lower than the first gen antihistamines, at least that's my understanding.

On the other hand, I've just gone on Ketotifen to help manage mast cell activation syndrome. It's an antihistamine and mast cell stabilizer that I decided to try for a number of reasons and I read first it was not anticholinergic. Just last night I was trying to get good information to confirm whether or not it's anticholinergic. It causes drowsiness in a lot of people for the first two weeks (recommended to gradually increase the dose) which may or may not be an anticholinergic effect?, and it's supposed to cross the BBB to help with histamine and mast cell issues in the brain. FWIW I don't notice *any* urinary retention like I do on other ACs, and controlling histamine and mast cells in the brain may have advantages for us (not that I'm recommending this drug absent known mast cell issues). So, additional data would help as to whether Ketotifen is anticholinergic, and even if so whether the mast cell stabilizing benefits outweigh the degree two which it may be anticholinergic.

[Rshircliff]

For the past several months I have been tapering off Clonazepam which I take for restless leg syndrome. I now think the restless leg is as a result of waking up with poor sleep and then tossing and turning to find sleep again. For 3 years I've been taking 1 mg every night and it worked great, but intuitively, I felt that I should try to go off it because it is a sedative and can cause memory problems. Reading about anticholinergic drugs here makes me very happy that I started the process.

It was very hard for me to wean myself. My dr said "just cut the pill in half and take half dosage for a week and you'll be fine going off it. It's has the same effect as a glass of wine". NOT. Like I've said before, my brain just loves its candy! However, I am now off of it after tapering down to .25 mg for several weeks and then .25 mg every other night.

My sleep quality is now poor. I wake up 4 - 6 times a night, always between 2 and 4 am, and at various other times. I also have sleep apnea, which my new sleep dr. said was a misdiagnosis because I'm not overweight. She ran another sleep study and low and behold, I have sleep apnea. I wasn't surprised, but she was.

According to this Stanford study, sleep apnea is related to Apoe4 gene.

Individuals with a particular genetic marker are twice as likely to suffer from sleep apnea -- a dangerous nighttime breathing disorder -- as people without the gene, say Stanford Medical Center researchers. The gene also predisposes carriers to the development of Alzheimer's and cardiovascular diseases.

The finding marks the first time that a specific gene has been linked to sleep disordered breathing, which may affect up to 10 percent of the population. The researchers say it also suggests that complex interactions exist between breathing patterns during sleep, cholesterol metabolism and mental status.

http://news.stanford.edu/news/2001/june13/apnea.html

The article goes on to say, LOL,

This is a marker you really don't want to have

So, my question here is this: is it that anticholinergic drugs, because they block acetylcholine, are more dangerous for us than a supplement like melatonin or 5-http or the others (including herbal teas with valerian root and the like) because these supplements don't block acetylcholine or do they?
OR
is anything that causes sedation bad for us?

I purchased some 5 mg melatonin and took it the other night. I still woke up during the night and in the morning I felt drugged. I slept about the same as when I drink Valerian root tea before bed, but I wake up more alert in the morning with the tea, so I'm sticking with the tea.

Would trying to drop down further to .125 mg dose of Clonazepam (and if .125 worked for me - haven't tried it yet) be a good trade-off for better sleep vs. the damage done by interrupted sleep, and outweigh any health risk of its anticholinergic properties ???