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"An Introduction to Botox - Its use for bladder & urethral disorders"

Contributor: Dr. Christopher Smith, Assistant Professor, Department of Urology, Baylor College of Medicine, TX USA
Date: October, 2003 - ICN Guest Lecture Series

Dr. Smith had hoped to appear in our lecture series but was called up by the Army Reserves to serve in Germany. He very kindly offered to take our questions by e-mail, including those submitted by patients in our message boards. We would like to this opportunity to express our sincere gratitude for not only his contribution to the ICN but for also working with our military abroad. We would also like to extend our gratitude to our sponsors Farr Laboratories (Makers of CystaQ & ProstaQ) and Algonot Labs (makers of Algonot, Cystoprotek and ProstaProtek). Their support of this lecture series has helped us to continue to provide the best information on IC to patients and providers throughout the world and at no cost.

---- GENERAL MECHANISM OF ACTION ---

What is BOTOX and when was it first discovered??

(Dr. Smith) Botolinum poisoning was first described in Germany in the late 1700's, usually the result of sausage poisoning. These patients often experienced paralysis. In the early 1900's, researchers Dickson and Shevsky discovered that Botolinum toxin appeared to inhibit nerve function. Finally, in 1949, Burgen discovered that the toxin works by acting at the nerve synapse. It blocks acetycholine, a neurotransmitter, thus preventing nerve transmission/function. In other words, it causes a temporary paralysis.

There are seven distinct neurotoxins known: A, B, C, D, E, F, and G. Since it's introduction to clinical use in the 1980's, BTX-A has been used successfully to treat various conditions, including blepharospasm (eyelid spasm), strabismus, focal dystonias, muscle spasms and spasticity, hyperhidrosis (excessive sweating) and achalasia (failure of a sphincter to relax).

In urology, BTX-A has been used for Detrusor External Sphincter Dysergia (DESD). These patients have impaired contractions of their sphincter. Its clinical effects begin within 2 to 3 days and reversible. Research studies have demonstrated that following urethral injection of Botox, voiding pressures decreased. We performed a prospective study on 21 patients referred to our clinic with voiding dysfunction. All patients were evaluated with videourodynamics. Follow up ranged from 3 to 15 months. Following urethral injection of botox, voiding pressures decreased an average of 38%. Sixty seven percent of patients reported an improvement of their voiding patterns and no complications or side effects were noted.

In the bladder, data has been accumulating on the clinical application of BTX-A, specifically for hyperreflexic bladders. One early study by Schurge and colleagues demonstrated a significant increase in mean maximum bladder capacity (296ml to 480ml) and a significant decrease in detrusor voiding pressure. A follow up study, long-term study by the same investigational team studied 87 patients with detrusor hyperreflexia reported clinical responses that lasted from 4 to 14 months and observed no adverse effects.

What other Urological/pelvic floor conditions has BOTOX-A been used for?

(Dr. Smith) BTX-A injections have extended beyond the realm of neurogenic bladders to patients with non-neurogenic voiding and storage disorders. Radziszewski and associates reported favorably on the effects of intravesical BTX-A injections in a pilot study of patients with either idiopathic bladder overactivity or functional outlet obstruction. Following intravesical or sphincteric BTX-A injections patients demonstrated resolution of incontinence and improved voiding efficiency.

Ziemann and colleagues presented their experience using BTX-A with severe urgency-frequency syndrome that was not responsive to other therapies. Four of seven patients responded to treatment with decreases in frequency and increased bladder capacity.

Does BOTOX remain in the specific organ or place injected or does it have the potential for migration?

(Dr. Smith) There was some old evidence using radiolabeled botulinum toxin that identified it in the central spinal cord but most investigators think this was a breakdown product and not actually functional botox. For the most part, most current evidence is that botox works peripherally. Because it is focally injected, systemic side effects are minimal.

Several IC patients have now participated in research studies for Botox. How could it be helping an interstitial cystitis or pelvic floor dysfunction patient??

(Dr. Smith) We are currently investigating Botox for refractory cases of IC on a case by case basis. I do not personally know of any ongoing IC trials. We would like to design a trial in the near future based on some early clinical results. However, I must caution that the word is still out on whether Botox will be an effective treatment option for patients with IC

Based upon your research experience, is BOTOX in the bladder completely reversible? How long does it take to reverse?

(Dr. Smith) Yes, typically effects will begin to wear off within 4-6 months although I have had patients with overactive bladders last as long as 9 months from one injection

Are urologists excited about this as a new therapeutic tool??? Is it gaining popularity?

(Dr. Smith) I think urologists want to get more excited about botox as a tool particularly for neurogenic and overactive bladders but the real problem is a reimbursement issue/lack of FDA approval. The word is still out on whether Botox will be an effective treatment option for IC

What is the short term versus long term therapeutic value of a therapy like BOTOX?

Botox is relatively easy to administer, requiring 30 minutes of IV sedation or general anesthesia, it takes effect within 5-7 days, and if it works it will last 4-6 months.

What is known about long-term effects of BOTOX used in the bladder? How do the long term studies look, if any??

(Dr. Smith) There are no clinical studies looking at long-term effects of botox (>5yrs) but some recent literature as well as personal experience suggest that patients tolerate multiple (up to 5) repeated injections with at least equal and maybe prolonged results with each injection.

--- CONSIDERING TREATMENT ---

Who qualifies for BOTOX? What do you look for in a patient??

(Dr. Smith) I use Botox as a later treatment option for patients with neurogenic or overactive bladders who have failed oral and, sometimes, intravesical therapies and are at the point where the next step would be invasive surgery (interstim vs bladder augmentation, etc)

What are the side effects if any?

(Dr. Smith) I have not personally identified any systemic side effects using Botox therapy. However, there are a few case reports where higher dose botulinum toxin or different formulations of botox led to generalized upper extremity weakness in a few spinal cord injured patients. There have also been a few case reports of stress urinary incontinence in patients after urethral injections although myself and Mike Chancellor have not seen any cases in over 50+ urethral injections

What's the regular course of treatment with BOTOX???

(Dr. Smith) Patients are treated as an outpatient under IV sedation or general anesthesia. In rare cases, a motivated patient can also be treated in the clinic with local anesthesia

How long does it take to feel the full effects of the treatment?

(Dr. Smith) In our experience, 5-7 days after bladder injection, 2-3 days after sphincter injection

Can it be used with other traditional bladder treatments like Elmiron or DMSO?

(Dr. Smith) As I stated earlier, Botox would be a last resort in a motivated IC patient who is willing to investigate this as a potential treatment option. In other words, these patients would have failed Elmiron/DMSO, and other treatments and all to the point where more invasive options are the only ones available (e.g. Interstim, cystectomy, etc).

Patients associate a BOTOX treatment with immediate pain relief? Would it potentially help reduce the symptoms for patients experiencing IC flares??

(Dr. Smith) I don't know-typically, patients who are treated with Botox are in significant pain at the time of treatment.

How can a patient find a doctor experienced with BOTOX? How should they look??

(Dr. Smith) Right now, I only know of a few doctors experimenting with botox for IC (myself, Michal Chancellor in Pittsburgh and Ray Rackley in Cleveland)-there may be more, I just don't know.

What type of training should a doctor receive to qualify??

(Dr. Smith) The actual procedure for injection is fairly simple and does not require significant instructions

Should a patient participate in a research study first??

(Dr. Smith) The real problem is funding-I would like to fund a pilot study of Botox in IC to see if there is some value in pursuing this as a treatment option. Currently, no one wants to fund (e.g. pay for drug which costs $500-600/vial)

--- DURING TREATMENT ---

How are the treatments performed?? Is it usually done with a hydrodistention, under anesthesia??

(Dr. Smith) Usually under anesthesia with hydrodistension

How many actual shots are given during a treatment? One patient reported 25 separate BOTOX injections into her bladder muscle during a treatment. That seems extreme.

(Dr. Smith) 20-30 injections. We need to spread toxin around the bladder, particularly the trigone and base of the bladder

Which type of anesthesia (general or spinal) is usually preferred?

(Dr. Smith) Whichever the patient is more comfortable with, we even use IV sedation.

--- POST TREATMENT ---

What does the patient feel after a treatment???

(Dr. Smith) Like after a hydrodistension

Is retention a problem after treatment??? Is it normal to send a patient home with a catheter for a few days?? Will patients run the risk of needing to cath themselves??

(Dr. Smith) In patients where a higher dose (200 versus 100 units) is used I sometimes have noticed problems with elevated residuals or even retention in rare cases. We try to avoid this by only injecting bladder base and trigone and using lower doses (100 units). I always instruct patients about potential for need to catheterize after surgery although, like toxin effect, this would be reversible as well.

W. Post op care??? What usually helps the patients feel comfortable??

(Dr. Smith) Pyridium, po narcotics

--- MISC. AUDIENCE QUESTIONS ---

Would BOTOX work as an intravesical instillation like DMSO or must it always be injected?

(Dr. Smith) As of now, it needs to be injected. Ideally, it would make treatment much more practical if it could be delivered by liquid instillation

The dermotologist told me that BOTOX need only be given about 4 times to have the effects last just about forever on the particular spots it was used. Is this true of the bladder too?

(Dr. Smith) There is some anecdotal evidence that some patients see longer effects with multiple treatments but no hard evidence and no evidence in literature that injection effects become permanent.

I read that after several treatments you need the injections less frequently, is this true?

(Dr. Smith) If it is, I would understand that the toxin will be less likely to disappear from the bladder... am I right?
As I stated before, some anecdotal evidence by clinicians but no hard evidence in literature that I know of

Can BOTOX hurt the liver??

(Dr. Smith) No evidence that I know of from bladder or urethral injections

One perception is that BOTOX can weaken or damage muscles. Is that true??

(Dr. Smith) Botox essentially weakens or can even paralyze muscles by impairing the nerves that timulate these muscles. However, the effects are reversible, and muscles eventually regain their normal/abnormal function.

Related Links:
A search of the National Library of Medicine (PubMed) web site will produce the latest research studies on the use of botox in the bladder.

The necessary disclaimer: Active and informed IC patients understand implicitly that no patient, or website or presentation on a web site should be considered medical advice. We strongly encourage you to discuss your medical care and treatments with a trusted medical care provider. Only your personal provider can and should give you medical advice. The opinions expressed by our speaker may not represent the opinions of the IC Network.

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