In this full-length doctor's interview, Christopher Patrick Smith, M.D., explains Botox is giving patients with overactive bladders their lives back
November 3, 2003
Ivanhoe's Medical Breakthroughs
Ivanhoe Broadcast News Transcript with Christopher Patrick Smith, M.D.,
Baylor College of Medicine, Houston, Texas
Botox for Your Bladder
How common is overactive bladder? Is it something that lots of people are dealing with and nobody knows about?
Dr. Smith: Very common. It's much more common than most people think. Over 20 million people in the United States probably have overactive bladder. Itís really the last urologic condition to come out of the closet. Obviously, itís a disorder that causes a lot of social problems. These patients have frequency, urgency, and then they have incontinence. Itís the worst type of leakage. When a patient has stress incontinence, it means that when they cough or sneeze, they leak urine. A patient can compensate for that by avoiding activities that would cause physical exertion or wearing appropriate protection. But a patient with overactive bladder that has urgency incontinence -- their incontinence comes out of nowhere. They have a bladder spasm and they canít make it to the bathroom in time, so they leak in their pants. It keeps patients from going out and doing their normal daily activities. But, a lot of patients are embarrassed because they donít know that thereís treatment available, they donít know how common it is within the population, and so they often hide these conditions and kind of live with it.
Besides interstitial cystitis, are there other causes of urgency incontinence?
Dr. Smith: Interstitial cystitis is a less common condition in which patients will have urgency, frequency, and then the thing that distinguishes them from overactive bladders is they have pain. But, most patients with whatís called idiopathic overactive bladder have the symptoms of frequency, urgency, and sometimes incontinence and they donít have pain. So, thatís the most common condition. Itís found in all age groups, although itís more frequent as people get older.
When you talk about frequency and urgency, how often do these people feel that they need to go to the bathroom?
Dr. Smith: Traditionally, frequent urination has been thought to be over 10 times a day within a 24-hour period, but some of these patients will be going 30 to 40 times in a day, you know, less than every 30 minutes to one hour, and theyíll be getting up at night every 30 minutes to one hour. So, you could see it could really incapacitate a patient. If we could reduce their times getting up at night from eight to four, we've really improved their quality of life. They can get some sleep and theyíre not feeling fatigued and tired and exasperated all day.
What have been the treatment options for urgency incontinence been in the past?
Dr. Smith: The mainstay for treatment is basically combination therapy between medications -- oral medications and behavioral therapy, so we use a combination of medicine and behavioral therapy. We have patients try to resist the urges over a period of time so they can extend the period between which they have these frequent episodes. The main traditional medications are anticholinergic medications. The problem with the medicine is that while theyíre effective, they can often have side effects such as dry mouth and constipation, which often preclude their long-term use.
You have dry mouth so you want to drink more and you have to go to the bathroom more?
Dr. Smith: Correct. Theyíve come out with longer-term formulations, 24-hour dosing, which has worked, but there still is a population that either does not benefit from the medication or they canít tolerate it. I think in this patient population, the Botox is a reasonable alternative.
Why Botox? What does that do?
Dr. Smith: These antimuscarinic or anticholinergic medications work on the muscle itself. They block the receptors that the acetylcholine, the chemical thatís released from nerve endings, causes the muscle to contract. So, these medications work on the receptor within the muscle. What Botox does is it paralyzes nerves that release these chemicals, so it works on the nerve side as opposed to the muscle side, and it essentially paralyzes the nerves so that the muscle does not receive any stimulation, the muscle weakens, and it reduces the spasticity that these patients have. It's been used for over 20 years by neurologists for spasticity of the skeletal muscles, so if you have an arm spasm or a shoulder spasm, it works, it gives a durable response over three to six months, but it is reversible. In the same way, weíre using it to target the smooth muscle within the bladder. Patients with spastic bladders or spastic urethras will inject those organs and the patients will also get a durable response from that. In some cases, even longer than in skeletal muscle; weíve had patients go over nine months with relief from one injection.
So, the longest has been nine months. What's the average amount of relief?
Dr. Smith: We usually tell patients three to six months, so if it is a treatment theyíre going to respond to, theyíre going to have a durable response in the sense that theyíre going to get three to six months, but it will reverse. A lot of patients like this option because they donít like the treatment thatís irreversible, so a treatment option that will give you a relatively long length of response but not yet be irreversible is meaningful for a lot of patients.
Botox obviously is toxic, so is this something that somebody can have every three to six months for the rest of their lives without risk?
Dr. Smith: Correct. Itís been in use for over 20 years. It is the most lethal toxin known to man, so itís very remarkable how scientists have turned this lethal toxin into important medical treatment options for patients. At least in the bladder, weíve used it over four to five years, and then in the urethral sphincter for 12 years. There are no significant local side effects, and there has not been any really appreciable systemic side effects, so itís pretty safe in the sense that there has been relatively few to no cases of systemic toxicity from the toxin. So, I think from that standpoint, itís a really low risk. In patients with underlying muscle weakness disorders such as myasthenia gravis or Lou Gehrigís syndrome, you want to not treat with Botox because it could exacerbate that underlying weakness, but otherwise, it's pretty much available to any patient. The only thing we worry about is not necessarily a risk, but with repeated use, thereís always a risk of antibody formation in the sense that patients will develop antibodies against the Botox where they wouldnít respond in the future. The risk of that is much lower now with the more pure formulations that are available today, and we usually like to space our injections out by at least three months, so if you inject less than a three-month duration, there may be an increased risk of antibody formation, but as far as local and systemic side effects, thereís not been any significant things weíve seen so far.
How does the procedure work?
Dr. Smith: For bladder injections, we do it through a cystoscope, a little small telescope that we insert through the urethra into the bladder, so there are no incisions into the skin. It's essentially invisible surgery. We use a small needle and we make multiple injections within the bladder wall to diffusely spread the toxin throughout the bladder itself so that there will be a global weakening of the muscle. Typically, it's an outpatient procedure. It can either be done under general anesthesia or under regional or local anesthesia even in your office. Patients will go home the same day, and typically the effects will be seen within five to seven days after treatment. If we inject the urethra, if weíre targeting the urethral sphincter, the effects are usually seen within two to three days.
Just because I donít know much about it, is that where you would use it for incontinence?
Dr. Smith: It wouldnít be incontinence. It would actually be the opposite. For the bladder, weíre targeting overactive bladder. For the sphincter, weíd be targeting a spastic sphincter that would be obstructing urine flow, so we can weaken the sphincter to allow patients to empty out appropriately and actually, thereís been a recent article that came out of Europe where investigators even used it to treat prostates, and weíre now investigating if itís a minimally invasive treatment option to treat BPH. Investigators found that it gave a 12-month durable response. It not only improved flow rates and improved symptoms, but it also reduced the prostate gland size and the PSA by over 50 percent, so that would suggest that it had an effect on not only the glandular obstructive component, the mechanical component to obstruction, but also the dynamic component which is related to smooth muscle contraction -- very interesting new innovative approaches for how Botox is being used.
You talked about conditions like ALS that you would not use this for? Who else can it be used for?
Dr. Smith: We donít use it as a first-line treatment, but patients that fail anticholinergic medication or antimuscarinic oral therapies who still have significant overactive bladder symptoms weíll treat. Patients with obviously neurogenic bladder, with spinal cord injury to stroke or multiple sclerosis, have a neurological reason for their bladder hyperactivity. Botox is a good option for those patients because it will avoid often a more invasive surgical procedure where weíll have to increase their bladder capacity by using intestines. So, we can inject with Botox, and it's kind of a medical way to increase the bladder capacity, decrease their frequency and their leakage of urine. So, overactive bladder and neurogenic bladders, weíre using it for spastic sphincters related to patients with spinal cord injury or multiple sclerosis. It's also been used for patients whose bladders didnít contract and they had to use a catheter to drain their bladders. It's been used to inject into their sphincters to lower their leak point pressure where the patient can actually void without the need to catheterize at all. So, it gives them an option of throwing away the catheter and being able to empty without a catheter itself. Also, it's now being targeted for patients with BPH. With interstitial cystitis, weíre actually investigating whether Botox can have an effect on the sentry nerves, not just the nerves that cause muscles to contract or spasm, but the nerves that transmit painful sensations.
Have studies been done on using it just for overactive bladder?
Dr. Smith: There have been multiple pilot studies. Unfortunately, to perform a randomized, large-scale trial, itís going to need the funding and so far, industry hasnít been real supportive of backing these approaches.
So, what have you seen?
Dr. Smith: Iíve seen that their conditions have improved remarkably well. Patients will often go throughout the night without having to get up to urinate or get up once or twice as opposed to eight or nine times. It really improves their quality of life. It reduces their fatigue because they donít have the struggle to rush to the bathroom. Potentially, it could even have an impact on decreasing fracture rates that are obviously associated with elderly patients getting out of bed and lurching for the bathroom. If you can reduce these urge episodes, these urges to run to the bathroom, then you may improve those conditions as well.
Ballpark, how many people have you treated with this?
Dr. Smith: Weíve treated with our department over 30 patients in the past year.
Anything else that you want to add?
Dr. Smith: I would say is that it's FDA approved, but it's off-label
use within urologic conditions, and so it's not guaranteed to be covered
by insurance companies. So, thatís something that we try to pre-certify
before we treat patients and then itís always an option. Thereís no guarantee
that itís going to be covered, but it is a treatment that is available
and has shown durable benefit.
Copyright © 2003, Ivanhoe Broadcast News, Inc.