Wednesday, July 3, 2019

Is dementia the price to pay to be dry?

First, a little background and terminology. Our brain cells talk to each other via “neurotransmitters.” One of these is a compound called acetylcholine. There are two relevant classes of medication that act on acetylcholine. One group are anticholinergic drugs, which block the effect of acetylcholine. These are used in many ways, and there are many subgroups. They are used to treat vertigo and nausea; they are used to prevent seizures; they include many of the older antidepressants, antipsychotics and antihistamines; they are antispasmodics for the intestine, and notably, they are used to treat urinary incontinence. The other class of drugs are cholinesterase inhibitors. The chemists among you will figure out that these block the breakdown of acetylcholine and so increase its effect. The best-known of this class are the drugs used to slow the progression of Alzheimer’s Disease.
It has been long-known that use of anticholinergics can cause confusion in elderly patients, and doctors have been taught to use these cautiously. What has not been known is if they have any long-term effect in patients who seem to tolerate their use. A study published online in JAMA Internal Medicine in June looked at this by studying a very large (30 million patients) British research database. They compared patients diagnosed with dementia with those who were not, matched by age and gender. They then looked at use of any of over 50 drugs with anticholinergic properties by type and by duration of use. They found that patients with dementia were much more likely to have been prescribed an anticholinergic drug over extended periods than were controls. The drugs that most clearly showed this effect were from the group that were expected to be used daily for a long time.
I would like to call your attention in particular to the group of drugs used to treat urinary incontinence. I do this because they are very widely advertised and widely-used by middle-aged and older women. They tend to be used for indefinite periods. They are also of marginal benefit at best. Many of the other drugs in this class are of less current concern because they are used only infrequently (anti-nausea, muscle relaxants) or because they have been largely replaced by newer drugs (tricyclic anti-depressants). Bladder problems are very common and while not life-threatening can be annoying and embarrassing. Oxybutinin (Detrol and other brands) is probably the most widely-used drug to treat overactive bladder. It universally causes a dry mouth, such that the increased thirst works against the desire to void less often.
While this was an “observational study,” and not a randomized trial, it has some inherent validity. We know that anticholinergics can cause confusion in some users. We know that acetylcholine is important in brain function. We know that drugs that increase acetylcholine have some benefit in dementia. My advice is to use these drugs only if other remedies have failed and only if the benefit is very strong. If your reaction is “well, it seems better than nothing,” I’d think twice. Maybe a pantie-liner would do as well and be safer.

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