[May 4, 2016] on the NEW MOBILITY website, it freaked me out! Especially when I read the linked study in JAMA Neurology that concludes that the use of these medications was associated with brain atrophy and brain dysfunction. Is this information new? Are taking these meds damaging my brain at my age? Can the effects on the brain be reversed if I stop taking the drug? And finally, are there alternatives that don’t affect the brain?
A. Although the title of the JAMA article is scary on face value, it is important to keep in mind that this is still a gray area. Here is some information that should put this study in perspective.
Perhaps the most important thing to consider is that the average age of the people in the study was 73. Also, the study had nothing to do with spinal cord injury. Also, urinary dysfunction used to be the leading cause of death among people with SCI. These days, thanks to multiple advances in the way we manage our bladder — including drugs to quiet spasms — it doesn’t even make the top three.
As the NM article explains, studies suggesting a link between anticholinergics and cognitive decline in older people have been around for quite a while. A PubMed search on “anticholinergics and dementia” pulls up pages of studies suggesting a link between anticholinergics and mental decline in older people going back at least as far as 2005.
Anticholinergics work by blocking acetylcholine, which stimulates muscle contractions, including the detrusor (bladder) muscle. When acetylcholine is blocked by a medication, it can’t stimulate the bladder and cause it to contract (spasm), which is a good thing. Anticholinergic medications used to treat neurogenic bladder include: Ditropan and Ditropan XL extended release tablets, Oxytrol Patch, Gelnique topical gel, Detrol and Detrol LA, Sanctura and Sanctura XR tablets, Enablex, Toviaz, and VESIcare.
A good overview of the recent anticholinergics and dementia study can be found in the May 9, 2016 article on WebMD by Kathleen Doheny (see resources). She writes that acetylcholine is also an important chemical in brain function, especially crucial for memory. This would explain why these medications often produce a foggy “brain-haze” side effect. Conversely, drugs used to treat Alzheimer’s and improve memory do the opposite. They act to increase the amount of acetylcholine.
It is important to note that of the 451 subjects in the study, only 60 were taking one or more anticholinergic meds. Although the study found a strong “link” between the drugs and dementia, it did not show that the drugs cause dementia. “There could be other things that explain the decline,” writes Doheny. Researchers she interviews echo the fact that multiple studies have suggested this link for quite a while.
In this latest article, Shannon Risacher, Ph.D, explains that there is no way to figure out an absolute risk for a single person. This is because among many variables, drug metabolism is unique to each person and has different effects on different people. She says there haven’t been any studies done that focus on a link to anticholinergics and cognitive decline in younger people, so it is difficult to know if the findings of this study apply. If the link to anticholinergic use in elderly people turns out to be cause and effect of dementia or Alzheimer’s, it’s likely because acetylcholine naturally declines with age, and older people are likely more sensitive to anticholinergics, she says.
The recent study did not look at whether or not the risk of developing cognitive problems disappears if you quit taking anticholinergics. Risacher says other studies have looked at this, but there is no consensus.
As for how this applies to managing spasms in a neurogenic bladder (bladder compromised by SCI or other nerve dysfunction), Dr. Michael Kennelly, director of urology at Carolinas Rehab in Charlotte, North Carolina, who has a specialty in SCI medicine, says, “At this point the level of evidence is not strong to make guideline changes or radical changes in bladder management. So far the evidence that using anticholinergics leads to dementia or Alzheimer’s is pretty thin, but it is gaining traction.”
Kennelly’s practice guidelines focus on how anticholinergics affect his patients’ cognition in the here and now. “We always try to minimize the use of anticholinergics, especially in at-risk groups, including children, elderly and patients with some cognitive impairment, such as MS, Parkinson’s Disease, stroke, etc.” he says. “We have known for quite some time that these drugs affect cognition, and we know that a lot of them cross the blood brain barrier.”
In addition to cognitive dysfunction, the side effect of dry mouth can lead to serious tooth decay, and blocking acetylcholine also causes muscles in the bowel to relax, causing constipation. At the present time, Kennelly says, there are two non-anticholinergic medication options to quiet the bladder — Mirabegron, sold in the United States as Myrbetriq, and Botox injections in the bladder.
Myrbetriq is a once daily pill that mellows bladder spasms but doesn’t affect acetylcholine; instead it quiets the bladder by stimulating Beta 3 receptors in the bladder’s muscle cells and doesn’t cause cognitive or other severe side effects that often accompany anticholinergics. It received approval by the FDA for treating overactive bladder in 2012.
The downside? “Myrbetriq is expensive and not all insurance covers it yet, or there may be a high co-pay,” says Kennelly. According to GoodRX.com, Mybertriq is covered by 91 percent of Medicare part D and Medicare managed plans. However, co-pays for a month’s supply range widely, from as low as $15 a month to $341 a month. Cash price for a month’s supply is around $303. Price-wise, Botox has become a bargain. GoodRX.com lists the Medicare co-pay for Botox at $172, and the procedure generally lasts four to six months or more.
Unfortunately, most insurers, including Medicare, won’t let you simply switch to Myrbetriq or Botox. The usual requirement is that you have tried to manage your bladder with an anticholinergic drug and it isn’t working for you. That may mean that you can’t tolerate the side effects or it doesn’t keep you dry at the maximum prescribed dose, says Kennelly.
“The most important thing to take away from this is you have to manage bladder spasticity, because if you don’t, you will likely ruin your urinary system, which can prematurely end your life,” says Kennelly. “The bottom line is, if you are worried about your memory or are having memory issues, avoid anticholinergics as best as possible. Ask your urologist about other options like Botox and Mybetriq.”
• Anticholinergic Meds May Cause Brain Damage, www.newmobility.com/2016/05/anticholinergic-brain-damage/
• Anticholinergic Study in JAMA Neurology, archneur.jamanetwork.com/article.aspx?articleid=2514553
• Dry Mouth and Tooth Decay, www.newmobility.com/2013/09/sci-medication-dry-mouth-and-tooth-decay/
• FDA Approves Botox for Bladder, www.newmobility.com/2011/10/fda-approves-botox/
• WebMD, Common Meds and Dementia: How Strong Is the Link? www.webmd.com/allergies/news/20160509/anticholinergic-drugs-dementia-link