Amitriptyline & IC Study

[BT2008]

My Google News Alert sent this article my way:

Amitriptyline in IC: Primary endpoint not met, but data offer hope

The largest trial to examine the efficacy, safety, and tolerability of amitriptyline as a treatment for interstitial cystitis failed to show a benefit of the drug versus placebo in an intent-to-treat analysis, but a secondary analysis examining study participants who tolerated high-dose therapy gave researchers a reason to call the study findings positive.

Researchers were also encouraged by the benefits of an educational/behavioral modification program that patients in both the placebo and treatment arms of the study received.

No statistically significant difference was seen in the primary endpoint—response to a global response assessment (defined as those study participants reporting "markedly" or "moderately" improved)—in patients receiving amitriptyline compared with those receiving placebo, as reported at a late-breaking news plenary session here. However, among study participants who were able to tolerate an amitriptyline dose of ≥50 mg, the response rate was 77% versus 53% in the placebo arm.

"It’s very difficult in an intent-to-treat trial to show a statistically significant efficacy effect in a drug that has significant side effects because people who don’t tolerate the drug drop out and they’re counted as failures," said Philip M. Hanno, MD, MPH, of the University of Pennsylvania, Philadelphia, who presented the data on behalf of the Interstitial Cystitis Collaborative Research Network. "From a broad perspective, my feeling is that it’s a very positive trial."

The multicenter, National Institutes of Health-sponsored trial enrolled 270 adult patients who were newly diagnosed with IC and previously untreated for the condition. Patients were randomized to an educational/behavioral management program plus placebo or the educational/behavioral program plus amitriptyline, titrated from a daily dose of 10 mg to 25, 50, or 75 mg daily over a 6-week period.

At 12 weeks, response rate on the global response assessment was not statistically different for amitriptyline and placebo recipients: 55% and 45%, respectively. However, secondary endpoints showed significant differences favoring amitriptyline on four measures: urinary frequency score, 24-hour voiding frequency, and the O’Leary-Sant Symptom and Problem Indices.

Nearly half (46%) of amitriptyline patients were able to tolerate the 50-mg dose throughout the study period. Adherence to a higher dose was associated with higher response rates, as was adherence to the educational/behavioral program.

"Even if they can only [tolerate] 25 or 30 mg, there’s a very nice improvement that can be expected in a majority of patients," Dr. Hanno said. "Based on the results of this study, you can make a case for starting with conservative behavioral management before adding a drug. Then if we’re going to add a drug, if that’s necessary, then consider the addition of low-dose amitriptyline."

My Source:
http://www.modernmedicine.com/modernmedicine/Modern+Medicine+Conference+News/AUA-Amitriptyline-in-IC-Primary-endpoint-not-met-b/ArticleStandard/Article/detail/595240?contextCategoryId=40184
Originating Source:
Urology Times

[KarenAnne]

Wow, that's my doctor, & I have had a good response to the amitriptyline. :o)
Thanks so much for posting this.

[BT2008]

KarenAnne,

I am very glad that you are responding well to the Amitriptyline, but you are one of only a few lucky ones! As the article states ...

"The largest trial to examine the efficacy, safety, and tolerability of amitriptyline as a treatment for interstitial cystitis failed to show a benefit of the drug versus placebo in an intent-to-treat analysis..."

We need to read the study carefully to figure out what the numbers provided in the article mean:

Out of the 270 people in the original study, the drug only ended up helping 96 patients, or 35.5%.

This number comes from the criteria provided in the article: 46% of the original 270 participants, or 124 people, were those who could tolerate high doses of the drug, and 77% of those, or 96 people, had a "positive response." That leaves 174 people--out of 270--who were not helped by the drug.

So, bottom line: Amitriptyline, as a treatment for interstitial cystitis, "failed to show a benefit ... versus placebo in an intent-to-treat analysis."

Which is obviously the correct conclusion to read from this study--but I am very concerned about the conclusion drawn in this article:"a very nice improvement that can be expected in a majority of patients." This is a very misleading comment. The only "majority" that experienced a "very nice improvement" was 77% of the 46% of the original 100%!! The statement quoted above reads as though "a majority of IC patients" can be expected to have "a very nice improvement" -- which was proven false by the conclusion of the original study!

If I had been in the study, I would have been one of the 174 people, or 64.5%, who were not helped by the drug! Not only was I unable to tolerate a high-dose (as well as the low dose) because it had very dangerous side-effects, but moreover, neither dose did anything for my pain.

~Beth

p.s. If my analysis of this article is in error...please feel free to correct me!!:)

[bluetart]

I glad I am not the only one that thought that article was foggy... I was like ...hmmm this dosn't add up. However I did try the medication and was unable to tolerate it but it was working.

[ICNDonna]

The way I read it is that it did make a difference with frequency --- which is a boon for an IC patient!

Donna

[SharonA]

I know that I and many others have been helped significantly by Elavil. I am glad my doctor suggested it and am glad it worked for me. Even from the very 1st dose of 10mg, it helped. By the next day, I noticed that most of my unrelenting, horror filled pain was gone. I have been taking 25mg since 2002 and it is still helping. I live a pretty normal life and Elavil is the only drug I take to make that happen.

I don't believe this test proved Elavil is a failure and, from the statement below, neither does Dr Hanno. Sure, some don't respond, but to those who do, it is a major accomplishment not to be made to seem inconsequential.

"Even if they can only [tolerate] 25 or 30 mg, there’s a very nice improvement that can be expected in a majority of patients," Dr. Hanno said. "Based on the results of this study, you can make a case for starting with conservative behavioral management before adding a drug. Then if we’re going to add a drug, if that’s necessary, then consider the addition of low-dose amitriptyline."

[Briza]

My thoughts are that 270 patients comprise a VERY small study.

My personal experience with Elavil is that it has helped me greatly, quickly, and at a very low dose of 10 mg for frequency, nocturia, and sleeping thru the night with minimal to no side effects, none dangerous to me personally, and any side effects were easily conquered with continued regular use. And I can personally attest to the fact that in my case this has NEVER been due to placebo effect.
And from reading MANY more than 270 patient stories/experiences with Elavil on this board is that it helps MANY with a variety of symtpoms, particulary for frequency, nocturia, and sleeping through the night. And many others for nerve pain or other symptoms.
Yes, of those many many patient stories that I have read here on this board, many did find success for symptom relief with Elavil but had to discontinue because of side effects, which may happen with ANY medicine. But even so, there are MANY who have found success with Elavil, side effects or not, for whichever symptom(s).
And finding a successful medicine for frequency ALONE, like Donna said, IS a boon for patients. There are many many IC patients who are members here on ICN who may not suffer from pain, but suffer from frequency so severe that it affects ALL aspects of their lives, and sometimes so badly that they lose or have to resign from their jobs. I have suffered from both severe pain and severe frequency....but by far it was the severe frequency that most affected my ability to work at times as well as other aspects of my life.

just my 2cents:)

[kadi]

I had huge improvement from only 10mg per night of Elavil, it dropped my frequency from 60x a day down to 20x. 20 mg brought my frequency down to 12-15x a day. This enabled me to continue working. I've had to seek out other meds since then to add to it to improve my overall quality of life with IC, but I don't know what I would have done (or would do without it).

My mother has IC - 10mg of Elavil at night, plus her hormone replacement therapy is all she takes to manage her IC. Another friend with IC only takes 10mg of Elavil & that restored her ability to work & function.

Just because a patient can't tolerate high doses or has to add another medication does not mean Elavil is a failure. It can still be very beneficial.

[BT2008]

Gosh, I hope I didn't open yet another "wasp's nest here"! I just wanted to present the article as I found it, and respond to the article itself.

Just for the record, "I" never said that Elavil was a "failure" for some IC sufferers, only for me. All I did was use the statistics of the original study, that "failed to show a benefit," and compared that to the findings of the secondary conclusion that claims "a very nice improvement that can be expected in a majority of patients." The first conclusion was not my opinion, this was the conclusion drawn by the researchers of the original study sponsored by the NIH. I only questioned the conclusion drawn by the researchers of the secondary study!

As far as being able to judge whether or not the original study "proves" anything one way or another, the article did not provide the specifics used to support the original conclusion. Rather, it only presented the specifics used for the secondary conclusion. So, is impossible to make a valid judgment call against the first finding just from the information provided in the article.

In case no one has noticed yet (!...lol), I am a very analytical person by nature, and always try to avoid "just seeing what I want to see". Instead, I work very hard to put all information such as this up to a test of logic and reason. And that's all I did here!:)

Also, did anyone notice that the secondary conclusion points out that it was the "conservative behavioral management" that those patients responded to the best, with the use of Amitriptyline being suggested only if "necessary." This leads readers to believe that "behavior modification" is the best first-line treatment, with drug therapy coming second. Again, not my opinion, just the conclusions drawn by the researchers of the secondary study.

I think we all need to be aware of how such studies are presented and how such conclusions are drawn--in this case, the conflicting conclusions in the article I cited in full. IC is a very serious disease, and our quality of life greatly depends upon such studies and the protocols that are oftentimes set by them. This study, however, was very suspect; the conclusion of the secondary study did not stand up to logical reasoning vis-a-vis the statistics used from the original study.

I am--like everyone else here--responding via my own experience. But, right after reading the article, I remembered that Sharon has often said that Amitriptyline has worked well for her for many years.

I truly wish it would have worked for me too...but it did not.

~Beth

[icnmgrjill]

This study had VERY confusing results. Yes, it was found ineffective when used as a single entity... but when combined with behavioral therapies, diet modification, stress management .... Phil Hanno said that over 75% would likely see a benefit from treatment.

I guess, ultimately, it depends upon your tolerance to the medication. I was one of those who couldn't tolerate it. It gave me a very irregular heart rate... and I think exacerbated a heart condition that runs in my family that I inherited. So, after a short period of time I was having a rapid, irregular heart rate from it and had to stop.

Jill

[MommaWuzzi]

I guess if you get a negative/not effective and you're really in love with your theory, you get really desperate to spin the results?

[MommaWuzzi]

I'm actually allergic (classic reaction - hives, itching, etc.) to Elavil, and did imipramine instead. When I ran out of imipramine the first time (didn't really think it was working that much) I discovered that my night-time frequency went from two to three times a night to every forty-five minutes to hour! I didn't notice any changes in PAIN level, and couldn't figure out what the difference was, because there wasn't a significant change in nocturia (it took it from four or five times a night to two or three) and why it went up so much after - I finally decided that it was possibly the SAM-e that was reducing nocturia a little bit before going off of it to start the other antidepressants... I'm actually going to discuss SAM-e dosage vs imipramine with the new doc...

[KarenAnne]

Even if a few case studies with a drug demonstrated marked improvement, & I was running out of options, then I would try the med. And it is so great that we can all talk like this & each have our own opinions. It helps to see everyone's side & get their idea on things.

Dr. Jerome Check has done case studies on dexedrine & pain syndromes that were not helped with standard treatment. He has not done large scale studies because his specialty is reproductive endcrinology. But even with his few case studies, dexedrine has proven successful with relieving IC pain & it's related symptoms. I have read his research & am keeping that option in mind.

But I too have responded favorably to the amitriptyline. I have not been able to tolerate more than 20 mg. so far, but I have felt better on the lower dose. I have been able to go out to a movie & dinner with my husband, out shopping, doing normal things I used to do. (And I'm not looking for a bathroom). I may have a few bad hours here & there, but with diet, ami. , prelief, & physical therapy, things are improved for the first time in eight months. The amitriptyline has allowed me to sleep THROUGH the entire night, maybe 1-2 times a week I get up once a night.

But this is just further proof that we all respond so differently to all the many therapies out there for IC. And thanks to Jill, the support leaders, & all of you, the rest of us are able to see all our options. Thanks BT for typing all that out.
Karen

[cinnamon8]

Am. was one of the first things that my doc gave me and it helped me get some much needed sleep.