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New Treatments for Overactive Bladder and Urinary Incontinence  

Nonsurgical treatment of involuntary bladder contractions, or overactive bladder. Basically, almost all treatment of this condition should be, and is, nonsurgical. It is only recalcitrant cases that would be treated surgically. Pharmacologically, the basis for treatment of these conditions basically is to try to use some parasympatholytic agents, primarily anticholinergics.

Antispasmodic agents are smooth-muscle relaxant agents that may or may not have anticholinergic properties. They are very useful as agents that may have a better therapeutic index, especially if they combine a spasmolytic as well as an anticholinergic action. We see that with hyoscyamine, or Levsin, Urispas, Levsinex and Levbid in this country, as well as with oxybutynin chloride, or Ditropan. These agents can be given two, three or four times a day, depending on their half life, to control involuntary bladder contractions. In addition to these are the tricyclic antidepressants, including imipramine or Tofranil.

To get around some of these side effects, two decades ago we saw the introduction of calcium channel blockers that didn't work all that well in normal therapeutic doses, but just recently we have seen the commercial introduction of tolterodine and another form of Ditropan that I will talk about in a moment. So after 24 years of not having any new agents, two years ago we got Detrol in this country, or Detrusitol, as it is known throughout the rest of the world. One of the really insulting things that the Upjohn Pharmacy did was that they made a determination right before the U.S. release that in the United States we weren't sophisticated enough to say Detrusitol; they thought it was way too many syllables and went with Detrol.

When we look at tolterodine compared to oxybutynin on the salivary glands of cats, we see a divergent curve when we look at dose versus inhibition. Inhibition of the bladder is better than inhibition of salivation in the cat, whereas for oxybutynin we see an inversion of the curves, where we have more of effect on salivation than we do on bladder effects. So with the release of this drug, the proposal was that it wasn't necessarily a stronger agent.

Last year, we got a different drug, or rather, a different delivery system for a known drug, and that is Ditropan-XL. Ditropan is administered in an oral system, an oral osmotic pump. It looks like a little pill, but it really is a pumping system that is excreted in the feces; it is never absorbed by the body. The casing just has drug and then it has a polymer in a semi-permeable membrane that absorbs water as this goes throughout the GI tract. As the polymer expands, the drug is just pushed out through a laser-drilled hole over the course of 21 hours.

In clinical trials for FDA approval, four trials submitted to the FDA, there was an overall reduction in urinary incontinence of eighty-four percent, which was significantly different than placebo. I think clinically, most interesting, is a study that I reported on , where we found that even in people who had taken prior medications, or even specifically had taken Ditropan.

You can take people who have had Ditropan before and give them Ditropan XL and it truly is like a totally new formulation and you can have a much improved response.

DDAVP is a different type of medicine to treat urinary incontinence and overactive bladder. Many patients have nocturia, an isolated complaint, or nocturnal enuresis as an isolated complaint. DDAVP can be used in adults, just like in kids and in a lot of ways, our elderly patients are a lot like kids. As we age, we start to lose antidiuretic hormone and we start to develop a reverse diuresis. Normally, you should concentrate your urine at night and on average, 20 year olds, for example, should have an hourly urine output.

It is important to remember that estrogen is a very effective medication when it comes to treating urgency, frequency, nocturia and even urge incontinence.

Instead of taking medicines by mouth, obviously we know we can take medicines by nonoral routes - patches, suppositories, bladder instillations. Some excellent work has been done that shows that if we avoid the first pass liver and small bowel effects, not just by medicines such as Ditropan-XL, but bladder instillations, we can be very successful. In the United States, we have seen the use of oxybutynin, or Ditropan, bladder instillations. In Germany, they use 2% xylocaine, put it in the bladder and say they resolve urge incontinence symptoms.

A lot of our patients hate the idea of self catheterizing, so before we had these two new agents we would often get stuck. One of my associates and I looked at 25 women that we gave Ditropan suppositories to - 5 mg Ditropan and polyethylene glycol. This was put in the rectum twice a day and we had them dose titrate from 5 to 20 mg per day. We improved thirty-six percent of people greater than fifty percent who had failed this oral medication before. We still had significant dry mouth in half of them and constipation in fourteen percent. So this was better for some people. Unfortunately, we had one woman with myotonic dystrophy.

The concept, in our practice, works in about forty to fifty percent of people who select to participate in this therapy. It is not an unselected group; people have to be motivated to do this, but it is certainly a group of people that we do not have in a research trial, we are not calling them up every week to remind them to do this and be compliant. What we do in this therapy is instead of the bladder bossing the brain around and telling you when to urinate and leaking urine before you can get to the toilet, because it is hard to run to the toilet.

Acupuncture has also been used and is a very effective technique, not surprisingly, in East Asia, as well as in New Zealand and Australia, where it is gaining great popularity. There are a number of trials. My favorite is from Chang, a urologist from Hong Kong. In a control trial of two acupuncture points, the actual point used for bladder SP6 posterior tibial versus ST36.