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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by tina on June 21, 2001, at 11:43:20
Hey guys and gals
I was given Elavil for irritable bowel syndrome about 6 months ago and it worked like a charm--for awhile.
I'm wondering if anyone else has had any good effects using AD's to treat IBS and if anyone has any theories about why the Elavil doesn't help anymore.
thanks
t
Posted by Willow on June 21, 2001, at 12:08:02
In reply to AD's for IBS??, posted by tina on June 21, 2001, at 11:43:20
I have a friend who's whole family almost has IBS. She was given an AD for a different reason, but found it helped with the IBS.
Your not alone.
Willow
Posted by super on June 21, 2001, at 15:10:06
In reply to Re: AD's for IBS??, posted by Willow on June 21, 2001, at 12:08:02
Tina,
Do you have IBS-C or IBS-D?
Super
> I have a friend who's whole family almost has IBS. She was given an AD for a different reason, but found it helped with the IBS.
>
> Your not alone.
>
> Willow
Posted by tina on June 21, 2001, at 15:37:50
In reply to Re: AD's for IBS??, posted by super on June 21, 2001, at 15:10:06
> Tina,
>
> Do you have IBS-C or IBS-D?
>
> Super
Thanks for the support guys.
Willow, I'm curious to know what med was given to your friend. I'd like to try it.
Super, I have both. It depends on the way the day goes.
My day is going pretty crappy at the moment. I'm having unbelievable cramping and I have had a headache for 4 days now. Nothing seems to help.
My self-esteem is at an all-time low due to the extra poundage I'm accumulating daily and there doesn't seem to be anything I can do about that either. I've tried to get back into the exercise thing only to have bad cramps cut my walk down to less than 5 minutes and when I've tried to strength train at home, I'm in pain after 1 rep. This sucks bigtime.
Any advice would be great. I'dlove to know what that med is Willow and Super, how goes the eating disorder battle? I haven't binged in 4 days and actually haven't wanted to eat anything at all due to the cramping.
I hope you two are doing ok
thanks again
T
>
> > I have a friend who's whole family almost has IBS. She was given an AD for a different reason, but found it helped with the IBS.
> >
> > Your not alone.
> >
> > Willow
Posted by Willow on June 21, 2001, at 16:34:45
In reply to Re: AD's for IBS?? Willow and Super, posted by tina on June 21, 2001, at 15:37:50
I don't see her that often, though we'll probably pump into each other at the beach through the summer. If I'm right it was one of the older ADs. Do you eat apples? Try eating two a day and a couple glasses of water. Don't eat greasy foods or milk on an empty stomach. Lots of carrot sticks or any other roughage will help. If you're going to be late with a meal eat a large banana and a small glass of milk.
Hope this helps!
Plain old tylenol can help with the pain.
Willow
Posted by medlib on June 21, 2001, at 18:01:49
In reply to AD's for IBS??, posted by tina on June 21, 2001, at 11:43:20
Tina--
I took Elavil for depression back when tricyclics and MAOIs were the only drugs available. It pooped out quickly for me, too--don't know why, but I have the impression that early poop-out is common. My best guess would be that its mechanism of action leads to downregulation of seratonin receptors, but I haven't investigated it. Some meds will have renewed effectiveness after a "hiatus," but I didn't find restarting Elavil helpful. It might be worthwhile to try other tricyclics.
Don't know how comfortable you are with medspeak, but I found a lit review (May, 2001) on the subject on Medscape. Basically, it said that the only *good* studies on ADs for IBS were on tricyclics (such as Elavil), but it did mention one study using citalopram (Celexa) and another using Paxil, among the SSRIs. Have you tried either of those?
I'd be happy to supply the URL, but Medscape is one of those sites that requires registration and I wasn't sure you'd want to hassle with that. As you're no doubt aware, there's beaucoup stuff out there on IBS; this review only briefly mentioned the psych connection to anxiety and early childhood traumas.
Ain't life just a pain in the ..(rear),sometimes?
Well wishes---medlib
Posted by fachad on June 21, 2001, at 20:18:15
In reply to AD's for IBS??, posted by tina on June 21, 2001, at 11:43:20
What dose of Elavil are you taking? My wife had severe IBS (constant pain, vomiting and dirrahea) that has been totally controlled by Elavil for over 7 years.
She had to take 225 mg/day at first when the IBS was in full flare. A few years later she was able to go down to 150 mg/day, but if she takes less than that she has the pain, the vomiting, and the dirrahea all over again.
Her GI doc was real reluctant to give her that high of a dose of Elavil at first, but it worked, and has kept working for 7 years.
If you have not pushed the dose to at least 150 mg/day, you may not be getting the full benefit of the Elavil.
> Hey guys and gals
> I was given Elavil for irritable bowel syndrome about 6 months ago and it worked like a charm--for awhile.
> I'm wondering if anyone else has had any good effects using AD's to treat IBS and if anyone has any theories about why the Elavil doesn't help anymore.
> thanks
> t
Posted by tina on June 21, 2001, at 23:34:14
In reply to Elavil for IBS, posted by fachad on June 21, 2001, at 20:18:15
wow fachad, 7 years, that's amazing. I only take 50mgs a day. It's all my psych would give me.
I tried increasing the dose myself but I just got very bitchy as the amount went up. Strange side effect but I hear it's pretty common with the tricyclics.
Thank you for the input though. It gives me hope. Perhaps another tricyclic would work better. I'll discuss options with my gp.
hugs
Tina
> What dose of Elavil are you taking? My wife had severe IBS (constant pain, vomiting and dirrahea) that has been totally controlled by Elavil for over 7 years.
>
> She had to take 225 mg/day at first when the IBS was in full flare. A few years later she was able to go down to 150 mg/day, but if she takes less than that she has the pain, the vomiting, and the dirrahea all over again.
>
> Her GI doc was real reluctant to give her that high of a dose of Elavil at first, but it worked, and has kept working for 7 years.
>
> If you have not pushed the dose to at least 150 mg/day, you may not be getting the full benefit of the Elavil.
>
>
>
> > Hey guys and gals
> > I was given Elavil for irritable bowel syndrome about 6 months ago and it worked like a charm--for awhile.
> > I'm wondering if anyone else has had any good effects using AD's to treat IBS and if anyone has any theories about why the Elavil doesn't help anymore.
> > thanks
> > t
Posted by tina on June 21, 2001, at 23:35:04
In reply to Re: AD's for IBS?? Willow and Super, posted by Willow on June 21, 2001, at 16:34:45
> I don't see her that often, though we'll probably pump into each other at the beach through the summer. If I'm right it was one of the older ADs. Do you eat apples? Try eating two a day and a couple glasses of water. Don't eat greasy foods or milk on an empty stomach. Lots of carrot sticks or any other roughage will help. If you're going to be late with a meal eat a large banana and a small glass of milk.
>
> Hope this helps!
>
> Plain old tylenol can help with the pain.
>
> WillowThank you Willow, I'll give your suggestions a try.
T
Posted by tina on June 21, 2001, at 23:38:38
In reply to Re: AD's for IBS?? » tina, posted by medlib on June 21, 2001, at 18:01:49
> Tina--
>
> I took Elavil for depression back when tricyclics and MAOIs were the only drugs available. It pooped out quickly for me, too--don't know why, but I have the impression that early poop-out is common. My best guess would be that its mechanism of action leads to downregulation of seratonin receptors, but I haven't investigated it. Some meds will have renewed effectiveness after a "hiatus," but I didn't find restarting Elavil helpful. It might be worthwhile to try other tricyclics.
>
> Don't know how comfortable you are with medspeak, but I found a lit review (May, 2001) on the subject on Medscape. Basically, it said that the only *good* studies on ADs for IBS were on tricyclics (such as Elavil), but it did mention one study using citalopram (Celexa) and another using Paxil, among the SSRIs. Have you tried either of those?
>
> I'd be happy to supply the URL, but Medscape is one of those sites that requires registration and I wasn't sure you'd want to hassle with that. As you're no doubt aware, there's beaucoup stuff out there on IBS; this review only briefly mentioned the psych connection to anxiety and early childhood traumas.
>
> Ain't life just a pain in the ..(rear),sometimes?
>
> Well wishes---medlibI have tried Celexa and Paxil, both made me so anxious and panic stricken that I couldn't tolerate either. The paxil gave me raging headaches too.
I have taken maoi's in the past and they worked great. I started the elavil because the maoi pooped out on me and, after a brief 'break', restarting it didn't do the trick.
thank you for the advice and I would love to read this article about IBS and AD's. You can send the URL to my email address if you like.
thanks again
tina
Posted by medlib on June 22, 2001, at 3:25:34
In reply to Re: AD's for IBS?? Medlib, posted by tina on June 21, 2001, at 23:38:38
Tina--
The Medscape article I mentioned is pasted below.
Hope you find something that helps! Regards---medlib
Digestive Disease Week 2001
Day 1 - May 20, 2001
New Therapeutic Insights Into Irritable Bowel Syndrome
Nicholas J. Talley, MD, PhD
Introduction
Currently, therapy for irritable bowel syndrome (IBS) remains a challenge. A recent systematic review concluded that there are few agents with proven efficacy for this disorder.[1] A meta-analysis suggested that loperamide was of established value for diarrhea, but not for pain in IBS.[2] Antispasmodics were also determined to be useful in this study, but in a recent and more comprehensive meta-analysis of these antispasmodic drugs (of which only hyoscyamine is available in the United States),[3] it was found that most failed to significantly improve abdominal pain (including hyoscyamine). Additionally, the quality of many of the trials remains uncertain.
It is within this setting that there remains continuing interest in novel therapeutic approaches for IBS. At this year's Digestive Disease Week meeting, which convened in Atlanta, Georgia, new data have been presented on the serotonin-modulating agents as well as on antidepressants and herbal therapies. This summary reviews and discusses some of this new and topical information.
Natural History
In order to interpret the results from clinical trials in IBS, the natural history of this disorder must be appreciated. There is a considerable placebo response in IBS that has been attributed, at least in part, to spontaneous remission of the disease.[1,2] The fact that IBS can remit spontaneously is supported by results of a study by Cadenas and colleagues[4] from Spain. These investigators included 38 patients in a prospective noninterventional cohort study; the Rome II criteria were used to identify patients with IBS, and these individuals were evaluated at entry initially and then subsequently, at 27-32 months later. Overall, 60% of subjects actually improved. More patients with constipation and alternating-type IBS no longer fulfilled the Rome criteria at follow-up (50% in both cases) compared with diarrhea-predominant IBS (only 10%). However, the placebo response does not seem to be different in diarrhea- vs constipation-predominant IBS in other trials, hence these results need to be viewed cautiously.
Of even more interest is the report on persistence of the placebo response during a 12-month controlled study of IBS by Northcutt and associates.[5] In this large, well-conducted study, 714 women who had either diarrhea-predominant IBS or an alternating bowel pattern were randomized to either active therapy or placebo for 12 months. (The actual therapy was not specified.) Notably, once the patients had stabilized, adequate relief, which was the primary endpoint, was consistently reported by 45% +/- 5% of patients in the placebo group over the 12 months of follow-up. This confirms the results observed with placebo in the 3-month treatment studies previously published,[6] but the persistence of the response was not anticipated. These results suggest that placebo can be an excellent therapy for a subset of patients with IBS over the long term, and clinicians should keep this in mind when planning management. An explanation for this prolonged placebo response seen in the clinical trial setting is unclear. However, trials that apply comprehensive follow-ups may actually be providing a form of psychological treatment in terms of reassurance and support; this hypothesis must be tested prospectively.
Therapeutic Options in Constipation-Predominant IBS
There has been increasing interest in testing new prokinetics in IBS, particularly with the demise of cisapride (although that drug only had an equivocal benefit, if any, in this setting).[1,2] Tegaserod is a partial 5HT4 agonist that modestly accelerates colonic transit and has been promising in constipation-predominant IBS.New Prokinetics -- Is There a Role for Tegaserod?
In a plenary session on intestinal disorders, Lefkowitz and colleagues[7] reported the results of a large, high-quality trial in women with constipation-predominant IBS. Overall, 1519 patients were randomized to either tegaserod (6 mg twice daily) or placebo for 3 months; a 4-week withdrawal period was built into this trial. The primary outcome was the patient's global assessment of relief, and a responder was defined as someone considerably or completely relieved of IBS symptoms.
Although use of tegaserod did lead to significant improvements in the primary endpoint (ie, subjective global assessment of relief) as well as in endpoints for abdominal pain and bowel habit, the effects were relatively modest (overall therapeutic gain, 5%). Moreover, the effects were greater at month 1 than at month 3, because the placebo response tended to increase over the duration of the trial. This finding may reflect the intensive monitoring of the study, an effect that has been observed in other clinical trials with similar methodology.[5] The drug was well tolerated; diarrhea was the only major side effect, and it increased in occurrence approximately 2-fold vs with placebo.Cisapride (a 5HT4 agonist with 5HT3 antagonist actions) rarely caused sudden death via QTc prolongation and induction of ventricular arrhythmias. Therefore, how safe is tegaserod? Rueegg and colleagues[8] reported that the frequency of the prolongation of the QTc was similar in tegaserod- and placebo-treated groups, based on data analyzed from 3 large, randomized controlled trials. These findings appear to support the case that tegaserod has a cardiac safety profile that is no different from placebo.
How consistent is the response to therapy with tegaserod? Muller-Lissner and associates[9] reviewed results from 3 placebo-controlled studies conducted on 3199 constipation-predominant IBS patients, of whom 92% were women. Findings suggested that female patients taking 12 mg per day of tegaserod tended to have a reproducible response to therapy. Only approximately 25% of those who had not responded in the first month became responders at the end of the 3 months. Therefore, if therapy was not successful by 4 weeks, the clinician could reasonably cease the treatment and look for an alternative; continuing therapy would unlikely be helpful. However, there did not appear to be any clinical predictors for either a response at month 1 or for a continued response. Men do not appear to benefit from tegaserod, and the reasons for this are currently not known.
Unfortunately, therapeutic options in constipation-predominant IBS remain relatively limited. There is evidence that fiber and fiber supplements are largely ineffective over placebo.[1,2] Moreover, the value of laxatives, based on clinical experience, is also unsatisfactory. Therefore, the new prokinetic tegaserod appears to show promise. However, it must be noted that on stopping therapy, patients rapidly return to baseline according to the results of the trial by Lefkowitz and coworkers.[7] Therefore, this medication does not change the natural history of IBS (in fact, no agent has been convincingly documented to do so).
Furthermore, the approach of intermittent, self-directed therapy has not been tested in any of the clinical trials, which may actually represent a more appropriate strategy than maintenance therapy for patients with intermittent IBS symptoms (who constitute the majority).
Therapeutic Options in Diarrhea-Predominant IBS
The management of diarrhea-predominant IBS similarly remains unsatisfactory.[1,2] Alosetron was withdrawn last year because of complications from severe constipation as well as ischemic colitis. However, alosetron appeared to be effective in diarrhea-predominant IBS, and indeed, recent evidence suggests that this drug improved not only IBS symptoms but also quality of life compared with placebo.[6,10]High-Affinity 5-HT3 Antagonist, Cilansetron
Another 5HT3 antagonist -- cilansetron -- has now been tested in patients with IBS. Caras and associates[11] reported the results of a study conducted in male and female nonconstipation patients with IBS from the United States.
These investigators conducted a double-blind, placebo-controlled trial using the endpoint of adequate relief of IBS symptoms. The results are interesting because they contrast with the findings on alosetron. That is, overall, 40% of patients had adequate relief on placebo compared with 62% on 1 mg of cilansetron; this difference was significant. They also found that the highest dose of cilansetron (16 mg) was significantly more effective than placebo, with a 62% response rate -- but the interim doses were not superior to placebo. By contrast, in published studies, higher doses of alosetron were not more efficacious. Even more interesting was the fact that the response rates were similar in both men and women, which contrasts sharply with the results obtained for alosetron (and tegaserod), in which case only women seemed to benefit. There were no cases of ischemic colitis reported during the study, although there is 1 known occurrence of possible ischemic colitis with this compound.Overall, these results are encouraging. Assuming that there are no serious side effects associated with this drug, it may indeed have a place in treating diarrhea-predominant IBS in the future. However, whether severe constipation and ischemic colitis are class effects of the 5HT3 antagonists remains unknown.
Antidepressants*
Antidepressants have been shown in a meta-analysis to be superior to placebo in treating IBS, but all of the studies have evaluated tricyclics rather than the newer antidepressants.[12]
Clouse and colleagues[13] reported the results of a meta-analysis of antidepressants in functional bowel syndromes. The study authors concluded that there was an 8-fold benefit for pain and a 4-fold benefit for global symptom improvement compared with control therapy. However, the quality of many of the trials has been questioned. Moreover, whether specific psychological disturbances or types of bowel habit predict response remains poorly defined.
Selective Serotonin Reuptake Inhibitors*
There are no randomized, controlled trials published on the value of selective serotonin reuptake inhibitors (SSRIs) in the treatment of patients with IBS.[14] Because these drugs tend to produce diarrhea, SSRIs may be most efficacious in constipation-predominant IBS. But again, this is a virtually untested concept.
Broekaert and colleagues[15] reported the results of a randomized, controlled trial with the SSRI citalopram. The study was unfortunately rather small, comprising only 14 patients with IBS who fulfilled the Rome II criteria. This was a crossover study, a design that has been criticized in the past because of methodologic concerns, such as an absence of the return of symptoms to baseline despite an adequate washout. The investigators also administered citalopram intravenously rather than orally, a strategy that may not provide generalizable results for clinical practice.The study authors found that citalopram did reduce the number of abdominal pain days as well as the severity of abdominal pain. It also reduced bloating frequency and severity, and global scores improved. Bowel habit, however, was not adequately assessed and subgrouping of IBS was not considered in the study design. Also of interest, these investigators did not show the drug to have had any effect on colonic sensation, as based on a barostat balloon study in the descending colon. So, presumably, if this drug is efficacious, it is acting centrally. Unfortunately, while the results of this study are intriguing, they are not definitive.
Creed and colleagues[16] compared the SSRI paroxetine with routine care and psychotherapy in a well-conducted, randomized controlled trial. They found that paroxetine was more effective than standard care at 12 months of follow-up, and was as efficacious as psychotherapy. This trial additionally supports the view that SSRIs are of therapeutic value in IBS. However, it should be noted that blinding of outcomes was not possible in this study; therefore, substantial bias may have been introduced despite careful attempts by the investigators to minimize this issue. Furthermore, only patients with severe IBS were included and therefore the generalizability of the results remains of concern. More work on SSRIs for IBS is clearly indicated. Although these agents may be of real therapeutic value, as supported by other anecdotal observations,[14] this has not yet been firmly established.
Alternative Strategies
There is increasing interest in alternative therapies for IBS. Indeed, a randomized controlled trial[17] of Chinese herbal medicine recently reported that this therapy was more effective than placebo, although there were 20 different preparations included -- therefore the "truly efficacious" agent or agents could not be identified.
Madisch and associates[18] reported their results with an herbal preparation (Iberogast) and evaluated its use in 157 patients with IBS. The trial tested a modified herbal preparation with 5 rather than 9 plant extracts, as well as a monoextract of bitter candy tuft and a placebo. The study authors found that patients on the modified herbal preparation had a significant improvement in terms of abdominal pain and global symptoms over that achieved with placebo. However, the monoextract was not superior to placebo. They did not observe any serious adverse reactions associated with treatment.Additional work is warranted to determine which plant herbal extracts may be of value in IBS. Furthermore, mechanistic studies are required with potentially active compounds to identify how they may work. Clearly, however, this area of study is moving out of the realm of pseudoscience and into that of true science, and may yield better management approaches for our patients in the future.
*The United States Food and Drug Administration has not approved this medication for this use.
References
Akehurst R, Kaltenthaler E. Treatment of irritable bowel syndrome: a review of randomised controlled trials. Gut. 2001;48:272-282.
Jailwala J, Imperiale TF, Kroenke K. Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. Ann Intern Med. 2000;133:136-147.
Poynard T, Regimbeau C, Benhamou Y. Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2001;15:355-361.
Cadenas FF, Villanueva A, Iglesias-Canle J, et al. Clinical course of irritable bowel syndrome (IBS): A 2-3 year follow-up study. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #4065]
Northcutt AR, Mangel AW, Hamm LR, et al. Persistent placebo response during a year-long controlled trial of IBS treatment. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3243]
Camilleri M, Northcutt AR, Kong S, et al. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet. 2000;355:1035-1040.
Lefkowitz, M, Ligozio G, Glebas K, et al. Tegaserod provides relief of symptoms in female patients with irritable bowel syndrome (IBS) suffering from abdominal pain and discomfort, bloating and constipation. Gastroenterology. 2001;120:P-11. [Abstract #104]
Rueegg PC, Baldauf CD, Dingemanse SA, et al. Tegaserod, a 5HT4 receptor partial agonist, devoid of significant electrocardiographic effects. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3257]
Mueller-Lissner S, Lefkowitz M, Shi YQ, et al. Early effect of tegaserod predicts continued efficacy in treatment of constipation predominant irritable bowel syndrome. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3259]
Watson ME, Lacey L, Kong S, et al. Alosetron improves quality of life in women with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol. 2001;96:455-459.
Caras S, Krause G, Biesheuvel E, et al. Cilansetron shows efficacy in male and female non-constipated patients with irritable bowel syndrome in a United States study. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #1138]
Jackson JL, O'Malley PG, Tomplans G, et al. Treatment of functional gastrointestinal disorders with anti-depressant medications: a meta-analysis. Am J Med. 2000;108:65- 72.
Clouse RE. Prakash C, Anderson RJ, et al. Antidepressants for functional gastrointestinal symptoms and syndromes: a meta-analysis. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3252]
Clouse RE, Lustman PJ, Geisman RA, et al. Antidepressant therapy in 138 patients with irritable bowel syndrome: a five-year clinical experience. Aliment Pharmacol Ther. 1994;8:409-416.
Broekaert D, Vos R, Gevere A-M, et al. A double-blind randomized placebo-controlled crossover trial of citalopram, a selective 5-hydroxytryptamine reuptake inhibitor, in irritable bowel syndrome. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3250]
Creed FH, Fernades L, Guthrie E, et al. The cost-effectiveness of psychotherapy and SSRI antidepressants for severe irritable bowel syndrome. Gastroenterology. 2001;120:A-115. [Abstract #619]
Bensoussan A, Talley NJ, Hing M, et al. Treatment of irritable bowel syndrome with Chinese herbal medicine. A randomized controlled trial. JAMA. 1998;18:1585-1589.
Madisch A, Holtmann G, Sassin I, et al. Herbal preparations in patients with irritable bowel syndrome: results of a double-blind, randomized, placebo-controlled multicenter trial. Gastroenterology. 2001:A-134. [Abstract #715]
Posted by fachad on June 22, 2001, at 8:45:49
In reply to Re: Elavil for IBS » fachad, posted by tina on June 21, 2001, at 23:34:14
Any M.D., whether GI, GP, or Pdoc, should know that 50 mg/day is really low dose for Elavil. It's below what would ever be considered an effective dose for depression, and some consider IBS to be a somatic manifiestation of depression.
If Elavil is not for you, IMHO, the other logical choices based on their actions at receptors involved in IBS would be doxepin (generic) or trimipramine (Surmontil, patent). Either one of these would probebly be effective for IBS, but again the dose may have to be in the 100 - 200 mg/day range if your IBS is severe.
There is also an EXTREMELY expensive patient medecine called ondansetron (Zofran) that is a very specific 5-HT3 blocker. It is marketed for nasuea and vomiting from cancer chemotherapy, and has been shown effective for IBS. But you'd better be wealthy, or have really good health insurance, because it's very costly. I'd try the other TCAs first.
Just my 2 cents.
> wow fachad, 7 years, that's amazing. I only take 50mgs a day. It's all my psych would give me.
> I tried increasing the dose myself but I just got very bitchy as the amount went up. Strange side effect but I hear it's pretty common with the tricyclics.
> Thank you for the input though. It gives me hope. Perhaps another tricyclic would work better. I'll discuss options with my gp.
> hugs
> Tina
> > What dose of Elavil are you taking? My wife had severe IBS (constant pain, vomiting and dirrahea) that has been totally controlled by Elavil for over 7 years.
> >
> > She had to take 225 mg/day at first when the IBS was in full flare. A few years later she was able to go down to 150 mg/day, but if she takes less than that she has the pain, the vomiting, and the dirrahea all over again.
> >
> > Her GI doc was real reluctant to give her that high of a dose of Elavil at first, but it worked, and has kept working for 7 years.
> >
> > If you have not pushed the dose to at least 150 mg/day, you may not be getting the full benefit of the Elavil.
> >
> >
> >
> > > Hey guys and gals
> > > I was given Elavil for irritable bowel syndrome about 6 months ago and it worked like a charm--for awhile.
> > > I'm wondering if anyone else has had any good effects using AD's to treat IBS and if anyone has any theories about why the Elavil doesn't help anymore.
> > > thanks
> > > t
Posted by tina on June 22, 2001, at 8:56:40
In reply to Re: IBS article, posted by medlib on June 22, 2001, at 3:25:34
Very interesting and informative medlib. Thank you for posting it. I'll research this a little more with my docs and on my own.
i appreciate it very much
tina> Tina--
>
> The Medscape article I mentioned is pasted below.
> Hope you find something that helps! Regards---medlib
>
>
> Digestive Disease Week 2001
> Day 1 - May 20, 2001
>
>
> New Therapeutic Insights Into Irritable Bowel Syndrome
> Nicholas J. Talley, MD, PhD
>
>
> Introduction
> Currently, therapy for irritable bowel syndrome (IBS) remains a challenge. A recent systematic review concluded that there are few agents with proven efficacy for this disorder.[1] A meta-analysis suggested that loperamide was of established value for diarrhea, but not for pain in IBS.[2] Antispasmodics were also determined to be useful in this study, but in a recent and more comprehensive meta-analysis of these antispasmodic drugs (of which only hyoscyamine is available in the United States),[3] it was found that most failed to significantly improve abdominal pain (including hyoscyamine). Additionally, the quality of many of the trials remains uncertain.
> It is within this setting that there remains continuing interest in novel therapeutic approaches for IBS. At this year's Digestive Disease Week meeting, which convened in Atlanta, Georgia, new data have been presented on the serotonin-modulating agents as well as on antidepressants and herbal therapies. This summary reviews and discusses some of this new and topical information.
>
>
> Natural History
> In order to interpret the results from clinical trials in IBS, the natural history of this disorder must be appreciated. There is a considerable placebo response in IBS that has been attributed, at least in part, to spontaneous remission of the disease.[1,2] The fact that IBS can remit spontaneously is supported by results of a study by Cadenas and colleagues[4] from Spain. These investigators included 38 patients in a prospective noninterventional cohort study; the Rome II criteria were used to identify patients with IBS, and these individuals were evaluated at entry initially and then subsequently, at 27-32 months later. Overall, 60% of subjects actually improved. More patients with constipation and alternating-type IBS no longer fulfilled the Rome criteria at follow-up (50% in both cases) compared with diarrhea-predominant IBS (only 10%). However, the placebo response does not seem to be different in diarrhea- vs constipation-predominant IBS in other trials, hence these results need to be viewed cautiously.
> Of even more interest is the report on persistence of the placebo response during a 12-month controlled study of IBS by Northcutt and associates.[5] In this large, well-conducted study, 714 women who had either diarrhea-predominant IBS or an alternating bowel pattern were randomized to either active therapy or placebo for 12 months. (The actual therapy was not specified.) Notably, once the patients had stabilized, adequate relief, which was the primary endpoint, was consistently reported by 45% +/- 5% of patients in the placebo group over the 12 months of follow-up. This confirms the results observed with placebo in the 3-month treatment studies previously published,[6] but the persistence of the response was not anticipated. These results suggest that placebo can be an excellent therapy for a subset of patients with IBS over the long term, and clinicians should keep this in mind when planning management. An explanation for this prolonged placebo response seen in the clinical trial setting is unclear. However, trials that apply comprehensive follow-ups may actually be providing a form of psychological treatment in terms of reassurance and support; this hypothesis must be tested prospectively.
>
>
> Therapeutic Options in Constipation-Predominant IBS
> There has been increasing interest in testing new prokinetics in IBS, particularly with the demise of cisapride (although that drug only had an equivocal benefit, if any, in this setting).[1,2] Tegaserod is a partial 5HT4 agonist that modestly accelerates colonic transit and has been promising in constipation-predominant IBS.
>
> New Prokinetics -- Is There a Role for Tegaserod?
> In a plenary session on intestinal disorders, Lefkowitz and colleagues[7] reported the results of a large, high-quality trial in women with constipation-predominant IBS. Overall, 1519 patients were randomized to either tegaserod (6 mg twice daily) or placebo for 3 months; a 4-week withdrawal period was built into this trial. The primary outcome was the patient's global assessment of relief, and a responder was defined as someone considerably or completely relieved of IBS symptoms.
> Although use of tegaserod did lead to significant improvements in the primary endpoint (ie, subjective global assessment of relief) as well as in endpoints for abdominal pain and bowel habit, the effects were relatively modest (overall therapeutic gain, 5%). Moreover, the effects were greater at month 1 than at month 3, because the placebo response tended to increase over the duration of the trial. This finding may reflect the intensive monitoring of the study, an effect that has been observed in other clinical trials with similar methodology.[5] The drug was well tolerated; diarrhea was the only major side effect, and it increased in occurrence approximately 2-fold vs with placebo.
>
> Cisapride (a 5HT4 agonist with 5HT3 antagonist actions) rarely caused sudden death via QTc prolongation and induction of ventricular arrhythmias. Therefore, how safe is tegaserod? Rueegg and colleagues[8] reported that the frequency of the prolongation of the QTc was similar in tegaserod- and placebo-treated groups, based on data analyzed from 3 large, randomized controlled trials. These findings appear to support the case that tegaserod has a cardiac safety profile that is no different from placebo.
>
> How consistent is the response to therapy with tegaserod? Muller-Lissner and associates[9] reviewed results from 3 placebo-controlled studies conducted on 3199 constipation-predominant IBS patients, of whom 92% were women. Findings suggested that female patients taking 12 mg per day of tegaserod tended to have a reproducible response to therapy. Only approximately 25% of those who had not responded in the first month became responders at the end of the 3 months. Therefore, if therapy was not successful by 4 weeks, the clinician could reasonably cease the treatment and look for an alternative; continuing therapy would unlikely be helpful. However, there did not appear to be any clinical predictors for either a response at month 1 or for a continued response. Men do not appear to benefit from tegaserod, and the reasons for this are currently not known.
>
> Unfortunately, therapeutic options in constipation-predominant IBS remain relatively limited. There is evidence that fiber and fiber supplements are largely ineffective over placebo.[1,2] Moreover, the value of laxatives, based on clinical experience, is also unsatisfactory. Therefore, the new prokinetic tegaserod appears to show promise. However, it must be noted that on stopping therapy, patients rapidly return to baseline according to the results of the trial by Lefkowitz and coworkers.[7] Therefore, this medication does not change the natural history of IBS (in fact, no agent has been convincingly documented to do so).
>
> Furthermore, the approach of intermittent, self-directed therapy has not been tested in any of the clinical trials, which may actually represent a more appropriate strategy than maintenance therapy for patients with intermittent IBS symptoms (who constitute the majority).
>
>
> Therapeutic Options in Diarrhea-Predominant IBS
> The management of diarrhea-predominant IBS similarly remains unsatisfactory.[1,2] Alosetron was withdrawn last year because of complications from severe constipation as well as ischemic colitis. However, alosetron appeared to be effective in diarrhea-predominant IBS, and indeed, recent evidence suggests that this drug improved not only IBS symptoms but also quality of life compared with placebo.[6,10]
>
> High-Affinity 5-HT3 Antagonist, Cilansetron
> Another 5HT3 antagonist -- cilansetron -- has now been tested in patients with IBS. Caras and associates[11] reported the results of a study conducted in male and female nonconstipation patients with IBS from the United States.
> These investigators conducted a double-blind, placebo-controlled trial using the endpoint of adequate relief of IBS symptoms. The results are interesting because they contrast with the findings on alosetron. That is, overall, 40% of patients had adequate relief on placebo compared with 62% on 1 mg of cilansetron; this difference was significant. They also found that the highest dose of cilansetron (16 mg) was significantly more effective than placebo, with a 62% response rate -- but the interim doses were not superior to placebo. By contrast, in published studies, higher doses of alosetron were not more efficacious. Even more interesting was the fact that the response rates were similar in both men and women, which contrasts sharply with the results obtained for alosetron (and tegaserod), in which case only women seemed to benefit. There were no cases of ischemic colitis reported during the study, although there is 1 known occurrence of possible ischemic colitis with this compound.
>
> Overall, these results are encouraging. Assuming that there are no serious side effects associated with this drug, it may indeed have a place in treating diarrhea-predominant IBS in the future. However, whether severe constipation and ischemic colitis are class effects of the 5HT3 antagonists remains unknown.
>
>
> Antidepressants*
> Antidepressants have been shown in a meta-analysis to be superior to placebo in treating IBS, but all of the studies have evaluated tricyclics rather than the newer antidepressants.[12]
> Clouse and colleagues[13] reported the results of a meta-analysis of antidepressants in functional bowel syndromes. The study authors concluded that there was an 8-fold benefit for pain and a 4-fold benefit for global symptom improvement compared with control therapy. However, the quality of many of the trials has been questioned. Moreover, whether specific psychological disturbances or types of bowel habit predict response remains poorly defined.
>
>
> Selective Serotonin Reuptake Inhibitors*
> There are no randomized, controlled trials published on the value of selective serotonin reuptake inhibitors (SSRIs) in the treatment of patients with IBS.[14] Because these drugs tend to produce diarrhea, SSRIs may be most efficacious in constipation-predominant IBS. But again, this is a virtually untested concept.
> Broekaert and colleagues[15] reported the results of a randomized, controlled trial with the SSRI citalopram. The study was unfortunately rather small, comprising only 14 patients with IBS who fulfilled the Rome II criteria. This was a crossover study, a design that has been criticized in the past because of methodologic concerns, such as an absence of the return of symptoms to baseline despite an adequate washout. The investigators also administered citalopram intravenously rather than orally, a strategy that may not provide generalizable results for clinical practice.
>
> The study authors found that citalopram did reduce the number of abdominal pain days as well as the severity of abdominal pain. It also reduced bloating frequency and severity, and global scores improved. Bowel habit, however, was not adequately assessed and subgrouping of IBS was not considered in the study design. Also of interest, these investigators did not show the drug to have had any effect on colonic sensation, as based on a barostat balloon study in the descending colon. So, presumably, if this drug is efficacious, it is acting centrally. Unfortunately, while the results of this study are intriguing, they are not definitive.
>
> Creed and colleagues[16] compared the SSRI paroxetine with routine care and psychotherapy in a well-conducted, randomized controlled trial. They found that paroxetine was more effective than standard care at 12 months of follow-up, and was as efficacious as psychotherapy. This trial additionally supports the view that SSRIs are of therapeutic value in IBS. However, it should be noted that blinding of outcomes was not possible in this study; therefore, substantial bias may have been introduced despite careful attempts by the investigators to minimize this issue. Furthermore, only patients with severe IBS were included and therefore the generalizability of the results remains of concern. More work on SSRIs for IBS is clearly indicated. Although these agents may be of real therapeutic value, as supported by other anecdotal observations,[14] this has not yet been firmly established.
>
>
> Alternative Strategies
> There is increasing interest in alternative therapies for IBS. Indeed, a randomized controlled trial[17] of Chinese herbal medicine recently reported that this therapy was more effective than placebo, although there were 20 different preparations included -- therefore the "truly efficacious" agent or agents could not be identified.
> Madisch and associates[18] reported their results with an herbal preparation (Iberogast) and evaluated its use in 157 patients with IBS. The trial tested a modified herbal preparation with 5 rather than 9 plant extracts, as well as a monoextract of bitter candy tuft and a placebo. The study authors found that patients on the modified herbal preparation had a significant improvement in terms of abdominal pain and global symptoms over that achieved with placebo. However, the monoextract was not superior to placebo. They did not observe any serious adverse reactions associated with treatment.
>
> Additional work is warranted to determine which plant herbal extracts may be of value in IBS. Furthermore, mechanistic studies are required with potentially active compounds to identify how they may work. Clearly, however, this area of study is moving out of the realm of pseudoscience and into that of true science, and may yield better management approaches for our patients in the future.
>
> *The United States Food and Drug Administration has not approved this medication for this use.
>
>
> References
> Akehurst R, Kaltenthaler E. Treatment of irritable bowel syndrome: a review of randomised controlled trials. Gut. 2001;48:272-282.
> Jailwala J, Imperiale TF, Kroenke K. Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. Ann Intern Med. 2000;133:136-147.
> Poynard T, Regimbeau C, Benhamou Y. Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2001;15:355-361.
> Cadenas FF, Villanueva A, Iglesias-Canle J, et al. Clinical course of irritable bowel syndrome (IBS): A 2-3 year follow-up study. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #4065]
> Northcutt AR, Mangel AW, Hamm LR, et al. Persistent placebo response during a year-long controlled trial of IBS treatment. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3243]
> Camilleri M, Northcutt AR, Kong S, et al. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet. 2000;355:1035-1040.
> Lefkowitz, M, Ligozio G, Glebas K, et al. Tegaserod provides relief of symptoms in female patients with irritable bowel syndrome (IBS) suffering from abdominal pain and discomfort, bloating and constipation. Gastroenterology. 2001;120:P-11. [Abstract #104]
> Rueegg PC, Baldauf CD, Dingemanse SA, et al. Tegaserod, a 5HT4 receptor partial agonist, devoid of significant electrocardiographic effects. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3257]
> Mueller-Lissner S, Lefkowitz M, Shi YQ, et al. Early effect of tegaserod predicts continued efficacy in treatment of constipation predominant irritable bowel syndrome. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3259]
> Watson ME, Lacey L, Kong S, et al. Alosetron improves quality of life in women with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol. 2001;96:455-459.
> Caras S, Krause G, Biesheuvel E, et al. Cilansetron shows efficacy in male and female non-constipated patients with irritable bowel syndrome in a United States study. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #1138]
> Jackson JL, O'Malley PG, Tomplans G, et al. Treatment of functional gastrointestinal disorders with anti-depressant medications: a meta-analysis. Am J Med. 2000;108:65- 72.
> Clouse RE. Prakash C, Anderson RJ, et al. Antidepressants for functional gastrointestinal symptoms and syndromes: a meta-analysis. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3252]
> Clouse RE, Lustman PJ, Geisman RA, et al. Antidepressant therapy in 138 patients with irritable bowel syndrome: a five-year clinical experience. Aliment Pharmacol Ther. 1994;8:409-416.
> Broekaert D, Vos R, Gevere A-M, et al. A double-blind randomized placebo-controlled crossover trial of citalopram, a selective 5-hydroxytryptamine reuptake inhibitor, in irritable bowel syndrome. Program and abstracts of Digestive Disease Week 2001; May 20-23, 2001; Atlanta, Georgia. [Poster #3250]
> Creed FH, Fernades L, Guthrie E, et al. The cost-effectiveness of psychotherapy and SSRI antidepressants for severe irritable bowel syndrome. Gastroenterology. 2001;120:A-115. [Abstract #619]
> Bensoussan A, Talley NJ, Hing M, et al. Treatment of irritable bowel syndrome with Chinese herbal medicine. A randomized controlled trial. JAMA. 1998;18:1585-1589.
> Madisch A, Holtmann G, Sassin I, et al. Herbal preparations in patients with irritable bowel syndrome: results of a double-blind, randomized, placebo-controlled multicenter trial. Gastroenterology. 2001:A-134. [Abstract #715]
>
>
Posted by tina on June 22, 2001, at 8:59:27
In reply to Re: Elavil for IBS, posted by fachad on June 22, 2001, at 8:45:49
I'll look into increasing the dose of elavil again or one of the other's that you mentioned. I really appreciate the advice, thank you.
take care
Tina> Any M.D., whether GI, GP, or Pdoc, should know that 50 mg/day is really low dose for Elavil. It's below what would ever be considered an effective dose for depression, and some consider IBS to be a somatic manifiestation of depression.
>
> If Elavil is not for you, IMHO, the other logical choices based on their actions at receptors involved in IBS would be doxepin (generic) or trimipramine (Surmontil, patent). Either one of these would probebly be effective for IBS, but again the dose may have to be in the 100 - 200 mg/day range if your IBS is severe.
>
> There is also an EXTREMELY expensive patient medecine called ondansetron (Zofran) that is a very specific 5-HT3 blocker. It is marketed for nasuea and vomiting from cancer chemotherapy, and has been shown effective for IBS. But you'd better be wealthy, or have really good health insurance, because it's very costly. I'd try the other TCAs first.
>
> Just my 2 cents.
>
>
> > wow fachad, 7 years, that's amazing. I only take 50mgs a day. It's all my psych would give me.
> > I tried increasing the dose myself but I just got very bitchy as the amount went up. Strange side effect but I hear it's pretty common with the tricyclics.
> > Thank you for the input though. It gives me hope. Perhaps another tricyclic would work better. I'll discuss options with my gp.
> > hugs
> > Tina
> > > What dose of Elavil are you taking? My wife had severe IBS (constant pain, vomiting and dirrahea) that has been totally controlled by Elavil for over 7 years.
> > >
> > > She had to take 225 mg/day at first when the IBS was in full flare. A few years later she was able to go down to 150 mg/day, but if she takes less than that she has the pain, the vomiting, and the dirrahea all over again.
> > >
> > > Her GI doc was real reluctant to give her that high of a dose of Elavil at first, but it worked, and has kept working for 7 years.
> > >
> > > If you have not pushed the dose to at least 150 mg/day, you may not be getting the full benefit of the Elavil.
> > >
> > >
> > >
> > > > Hey guys and gals
> > > > I was given Elavil for irritable bowel syndrome about 6 months ago and it worked like a charm--for awhile.
> > > > I'm wondering if anyone else has had any good effects using AD's to treat IBS and if anyone has any theories about why the Elavil doesn't help anymore.
> > > > thanks
> > > > t
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