A 54-Year-Old Woman With Constipation-Predominant Irritable Bowel Syndrome

DR REYNOLDS: Mrs G is a 54-year-old woman with abdominal pain and discomfort associated with constipation. Her bowel difficulties began in early childhood when she did not feel comfortable moving her bowels in public restrooms. Her symptoms diminished during her teenage years but began again in her 20s; over the past several years her constipation has become more problematic.

She has experienced bloating, generalized abdominal discomfort, and an inability to eat large meals. She experiences mild lower abdominal cramps while moving her bowels; she does not have any diarrhea. Mrs G has used many different over-the-counter laxatives including osmotic and stimulant laxatives; those products have typically improved her bowel regularity for a short time, but with prolonged use have stopped working. After she was diagnosed with osteoporosis several years ago, Mrs G, who had always been very small, began trying to gain weight as one measure to improve her bone strength. She was not able to gain weight because she felt bloated with small amounts of food. She tried to eat frequently, but continued to have abdominal symptoms.

After seeing an advertisement on television, Mrs G requested prescription medication for her symptoms. Her primary care physician referred her to a local gastroenterologist who agreed that Mrs G had constipation and irritable bowel syndrome (C-IBS), and she began a trial of tegaserod. She has had significant improvement in her symptoms and now moves her bowels daily. Mrs G would prefer not to take medication regularly. However, her attempt to stop the medication met with a complete return of her previous symptoms.

Mrs G has a history of osteoporosis with a T score of −3.2 at the femoral neck; an evaluation looking for secondary causes of osteoporosis was negative. She has Raynaud phenomena in her fingers. She had 2 pregnancies resulting in vaginal births; her menopause began about 10 years ago. Mrs G had a benign left ovarian cyst removed in the 1970s.

Mrs G's only medications are alendronate, calcium, vitamin D, and tegaserod.

Mrs G's family history is significant for a grandfather with rectal cancer and an aunt with breast cancer. She lives with her husband; her 2 children are grown. She works as a professional. She began exercising regularly about a year ago, drinks socially, and does not use nonprescription drugs. She has commercial medical insurance.

On physical examination, Mrs G is a pleasant, well-developed, thin woman. She is 58 inches tall and weighs 72 lb (body mass index, 16.2). Her abdomen shows normal bowel sounds and is soft, nondistended, and without masses. Rectal examination shows normal tone without hemorrhoids. On bear down she has normal descent of the pelvic floor, with no paradoxical contractions of the puborectalis muscle or the external anal sphincter. Her neurological examination results are normal.

Laboratory studies reveal normal values for complete blood cell count, glucose, calcium, thyroid-stimulating hormone, vitamin D, tissue transglutaminase antibody, and erythrocyte sedimentation rate. A colonoscopy performed 2 years ago was normal.

I can remember as a child going to nursery school and holding in a bowel movement because I didn't want to go outside of my house.

Throughout my teens and early adulthood, the problem came and went depending upon different conditions, stress levels, whatever. However, for the past 2 ½ years, the problem became increasingly worse. I really was more constipated with frequent episodes of abdominal pain and bloating, and I had a decrease in appetite. I think as I’ve become older I manage stress in a whole different way. And I feel that I am a relatively calm person. So to me it's very interesting that the past 2 ½ years, which really have not been beyond the norm for me as far as stress goes, have been the most difficult with my bowels.

If I was only able to move my bowels once every 10 days then my clothing felt tight, my stomach felt uncomfortable. I also had frequent pain in my abdomen. I felt that from the time I got up until I went to sleep that I just had this constant feeling of fullness and discomfort. And just this feeling sometimes that I had to go to the bathroom but then I couldn’t, so there was a lot of straining and just a general feeling of malaise because of not being able to go to the bathroom daily, or even a few times a week.

I spoke with my doctor about tegaserod because I saw the ad on TV and I said that part of my difficulty in gaining weight was that I had no appetite because of the constipation problem. She did not want to prescribe tegaserod without my having an evaluation.

I have been able to gain about 5 lb since I’ve been on the new medication. I’m actually hungry. I eat small meals throughout the day, so I keep a jar filled with different kinds of snacks, fruits, nuts, health bars. And I also, as soon as I feel that I have to go to the bathroom, I just go. Whereas in the past, I might have said, well, I’ll go later. I don't do that. If I have a bigger meal, clearly my stomach is full and it gets a little bloated, but I think that's probably pretty normal.

What really happens with this particular medication further down the road? I think that needs to be studied more for those of us who look at it as a long-term solution to an irritating problem. I don't know that I would call it a serious problem, it's more an irritating problem.

What is the spectrum of symptoms in IBS? What evaluation should primary care physicians perform before making the diagnosis of IBS? Can the diagnosis be made purely on clinical grounds? What are the causes of C-IBS? What behavioral treatments and medications have been shown effective for C-IBS? Mrs G, like many patients, requested a medication because she saw it advertised on television. How has direct-to-consumer advertising affected use and prescribing of such drugs? What do you recommend for Mrs G?

DR LEMBO: Mrs G's case raises a number of common and interesting issues in the management of patients with C-IBS.

Irritable bowel syndrome is a functional gastrointestinal disorder characterized by chronic or recurrent abdominal pain or discomfort, usually in the lower abdomen, which is associated with disturbed bowel function (ie, diarrhea or constipation alone or alternating) and feelings of abdominal distention and bloating.¹ Between 10% and 15% of the population in Western societies report these symptoms² ; however, only 30% ever seek medical attention for their symptoms.³ Nevertheless, IBS is still one of the most common reasons for consultation with a primary care physician or a gastroenterologist.

In the United States alone, IBS results in more than 3.5 million office visits and 2 million prescriptions per year.⁴ Direct medical costs for individuals with IBS symptoms are nearly 75% greater than for individuals without gastrointestinal symptoms,⁵ while total medical costs (direct and indirect) are estimated at nearly 40% higher.⁶ Although Mrs G reports that her symptoms did not interfere with her daily life, overall absenteeism from work or school is 3 times higher in individuals with IBS symptoms than in those without IBS, which is comparable to the flu and common cold.⁷

Irritable bowel syndrome has a significant negative impact on health-related quality of life.⁸ In a recent study, IBS patients scored significantly lower on all scales of a standard health related questionnaire (36-item Short-Form health survey [SF-36]) in comparison with the general population. Patients with IBS had similar or worse quality of life scores on the SF-36, except for physical functioning, than patients with gastroesophageal reflux disease and diabetes.⁹

Irritable bowel syndrome is more likely to affect women than men by a ratio of approximately 2:1. Irritable bowel syndrome is also more common in young adults¹⁰ than in older people, although it can occur at any age. For example, a study from the Mayo Clinic in Olmsted County, Minnesota, found that the prevalence of IBS in residents older than 65 years was 11% compared with 17% in people between the ages of 30 and 64 years.³ Women with IBS tend to report more symptoms of constipation and abdominal discomfort, especially bloating, as Mrs G does, while men with IBS report more diarrhea.¹¹

As is the case with Mrs G, upper gastrointestinal symptoms are commonly associated with IBS. Community-based surveys have found between 29%¹² and 90%¹³ of individuals with IBS have concomitant early satiety or upper abdominal discomfort. Individuals often will alternate between IBS and dyspepsia. For example, a longitudinal study¹⁴ found that 22% of individuals with IBS symptoms on an initial survey were experiencing dyspepsia 1 year later, while 16% of those with dyspepsia symptoms initially were experiencing IBS symptoms after 1 year.

Although not the case with Mrs G, individuals with IBS frequently have other intestinal and extraintestinal symptoms, including urinary frequency and urgency (especially in women), sexual dysfunction, fibromyalgia, dyspareunia, poor sleep, lower back pain, headaches, and chronic fatigue.¹⁵ The number of these extraintestinal symptoms present in individuals with IBS tends to increase with the severity of IBS.¹⁶ Psychological disturbances, such as anxiety and depression,¹⁷ are more common in individuals with IBS who seek medical consultation for their IBS symptoms than in those with similar symptoms who do not seek care for them, emphasizing the point that psychological disturbance may amplify IBS symptoms and affect health care–seeking behavior but is not sufficient to explain IBS symptoms.

The diagnosis of IBS is based on the identification of characteristic symptoms, such as the presence of abdominal pain or discomfort associated with alteration in bowel function, bloating and the sensation of incomplete evacuation after bowel movements, and the exclusion of organic disease. Symptom-based criteria for IBS have been evolving since 1978 when Manning and colleagues showed the usefulness of 6 symptoms (Manning criteria) in distinguishing patients with IBS from patients with organic diseases.¹⁸ More recently, consensus criteria for diagnosing IBS were developed (Rome I criteria)¹⁹ and subsequently modified in what is known as the Rome II criteria²⁰ for IBS ( Article ). Prevalence of IBS using the Rome II criteria is considerably lower than using the Rome I or Manning criteria.²¹ General practitioners tend to diagnose IBS based on the presence of unexplained multiple symptoms that have been present for an extended period of time.²² Unlike patients with chronic constipation alone, patients with C-IBS have significant abdominal pain or discomfort, although overlap between these entities exists.

Manning Criteria¹⁸

Rome I Symptom Criteria for IBS¹⁹

Rome II Symptom Criteria for IBS²⁰

Patients who have typical symptoms of IBS without “red flags” (ie, significant weight loss, blood in stools, age >50 years, family history of colon cancer or inflammatory bowel disease, fevers, or anemia), like Mrs G was at the time of her diagnosis, do not require extensive diagnostic tests to exclude common organic diseases masquerading as IBS.²³ The positive predictive value for the diagnosis of IBS in patients referred to a gastroenterology clinic using the Rome I criteria¹⁹ and excluding “red flags” was 98% over 1-year follow-up.²⁴ Other studies that have followed up patients over many years also confirm that the application of IBS criteria with limited diagnostic tests rarely leads to a later revision in diagnosis.²⁵

The 2002 Clinical Practice Committee of the American Gastroenterology Association recommended performing a serum chemistry panel, complete blood cell count, stool examination for ova and parasites, fecal occult blood test, erythrocyte sedimentation rate, and albumin level in patients with suspected IBS,¹ although the utility of performing even these diagnostic tests is debatable.²⁶ For example, a retrospective review of diagnostic tests performed on 196 patients with new-onset IBS symptoms found the yield of most routine blood tests (such as liver tests, complete blood cell count, and a thyroid panel) to be less than 1%.²⁷ The yield of performing a flexible sigmoidoscopy and barium enema or colonoscopy in these patients was approximately 1%, although the chance of finding structural lesions unrelated to IBS symptoms, such as colonic polyps, was much greater.

Since these guidelines were established, several studies have suggested that celiac disease may be more common in patients with suspected IBS,²⁸ and that screening for celiac disease (eg, serum tissue transglutaminase antibody) may be cost-effective,²⁹ especially in patients with IBS and diarrhea. However, further studies are necessary prior to recommending celiac testing routinely in evaluation of IBS.²³

Current guidelines by the Clinical Practice Committee of the American Gastroenterology Association recommend annual fecal occult blood testing, colonoscopy every 10 years, or flexible sigmoidoscopy every 5 years for colorectal screening for all individuals older than 50 years who do not have risk factors that warrant routine colonoscopy.³⁰ In the case of Mrs G, who is older than 50 years, a colonoscopy had been performed and was unremarkable. However, a colonoscopy would not have been recommended for Mrs G had she been younger than 50 years at the time of her presentation, since a colonoscopy is not necessary to exclude other illnesses in young patients at the time of their diagnosis.

Patients should only be referred to a gastroenterologist when an IBS diagnosis is uncertain or when “red flags” are present, not merely to confirm the diagnosis.

Patients with C-IBS have slower colonic and small bowel transit and fewer high-amplitude propagating contractions³¹ than people without IBS. Likewise, people with C-IBS tend to have lower pain thresholds to balloon distention in the rectum and elsewhere in the gastrointestinal tract,³² which may be due to recruitment of silent nociceptors in the gut, increased excitability of the neurons in the dorsal horn of the spinal cord, or differences in the way the brain modulates afferent signals.³³ Life stress, psychological state, social support, and coping strategies are important in the pathophysiology of IBS in some patients,³⁴ but they are not the sole contributors to the development of IBS.

Irritable bowel syndrome is more likely to occur after infectious gastroenteritis,³⁵ especially in women, those younger than 60 years, and those who have had severe gastroenteritis. These patients have increased enterochromafin cells, T lymphocytes, and gut permeability.^{36 - 37} Most patients who develop IBS symptoms following an enteric infection have a diarrhea-predominant bowel pattern, although constipation frequently is also present.

Several studies have reported a high prevalence of small bowel bacterial overgrowth.^{38 - 40} The production of methane gas by intestinal bacteria appears to be associated with constipation.⁴¹ Treatment of the small bowel bacterial overgrowth with antibiotics seems to improve IBS symptoms in some patients, especially when the lactulose hydrogen breath test result becomes normal.⁴² However, patients with C-IBS do not appear to respond as well as patients with diarrhea or alternating bowel habits.⁴³ Altering intestinal flora with probiotics has had varying success in improving IBS symptoms.^{44 - 45}

Serotonin as well as other neurotransmitters and hormones have been proposed to have an important role in IBS. Preliminary evidence suggests that women with diarrhea and IBS have increased serotonin levels in plasma.⁴⁶ Conversely, patients with C-IBS may have decreased immunoreactivity of the selective serotonin transporter (SERT) protein.^{47 - 48}

The first step in treating patients with C-IBS is to establish a therapeutic patient-physician relationship, reassuring the patient about the benign nature of the disease, and recommending general dietary and lifestyle modification (eg, smoking cessation, regular sleep and exercise, and avoiding foods known to affect the function of the gastrointestinal tract such as alcohol and caffeine). Likewise, encouraging patients to elevate their feet while defecating and to take advantage of the morning postprandial gastrocolonic response may be prudent, although no studies have been published documenting the effectiveness of these recommendations. Patients who continue to experience symptoms may be candidates for pharmacological and/or behavioral treatments (Table).

Fiber and Bulking Agents. Dietary fiber can improve symptoms in patients with mild to moderate constipation; however, its role in the treatment of C-IBS is less clear since fiber seems to improve some IBS symptoms and exacerbate others. A recent systematic review of 17 studies concluded that the benefits of fiber in the treatment of global IBS symptoms are marginal and that fiber has no effect on the relief of abdominal pain.⁴⁹ Studies that used soluble fiber (eg, psyllium, ispaghula, calcium polycarbophil) showed it to be more effective in treating C-IBS than studies that used insoluble fiber (eg, corn, wheat bran)⁴⁹ and, in some cases, insoluble fiber may have worsened symptoms of C-IBS.

Nevertheless, because of its low cost and morbidity, an adequate trial of dietary fiber, especially soluble fiber, should be the first-line agent in most patients with C-IBS. To reduce adverse effects and improve adherence, patients should be instructed to gradually increase their dietary fiber intake to approximately 20 to 25 g per day over several weeks. Initially, foods rich in soluble dietary fiber should be increased (eg, most fruits, oats, and barley); if results from this therapy are disappointing, commercially packaged fiber supplements can be tried. Mrs G reports a diet high in fiber, including an adequate trial of soluble fiber, as a treatment for her C-IBS.

Laxatives. To date, no controlled trials have evaluated laxatives for IBS. Although the effectiveness of laxatives in chronic constipation is generally accepted,⁵⁸ the data in clinical trials are not as convincing.⁵⁹ Laxatives generally do not treat abdominal pain associated with IBS and, therefore, they are unlikely to provide global relief of symptoms in most patients with C-IBS like Mrs G.

Nevertheless, anecdotal experience suggests that laxatives, particularly osmotic laxatives, may be helpful in some patients with C-IBS¹ and were reasonable to consider for Mrs G. Osmotic laxatives are poorly absorbed substances that result in secretion of water in the intestine and include salts (eg, magnesium and phosphate), disaccharides (eg, lactulose), sugar alcohols (eg, sorbitol or mannitol), and high-molecular-weight polyethylene glycol (PEG) (eg, Miralax, glycolax). Osmotic laxatives generally take several days to work. Because salts are partially absorbed, patients with renal insufficiency or cardiac dysfunction can experience electrolyte and volume overload from absorption of sodium, magnesium, or phosphorus. A Cochrane Review–based meta-analysis of “high-quality” studies confirmed the safety and efficacy of PEG laxatives for the treatment of chronic constipation.⁵⁰ Long-term use of PEG appears to be well-tolerated without significant adverse effects.⁶⁰

Stimulant laxatives increase intestinal motility and intestinal secretion and include diphenylmethanes (eg, phenolphthalein, bisacodyl, and sodium picosulfate) and anthraquinones (eg, cascara, aloe, and senna). They begin working within hours but are frequently associated with abdominal cramps and watery stools and therefore are generally not well tolerated by patients with C-IBS. Pseudomelanosis coli is a benign brown-black pigmentation of the colon mucosa that results from the administration of anthraquinone laxatives (the pigmentation is caused by the accumulation of apoptic colonic epithelial cells that have been phagocytosed by macrophages). Emollients (eg, mineral oil) and stool softeners (eg, docusate) help to lubricate and soften stool and may be helpful in mild constipation.⁶¹ Despite common beliefs, it is unlikely that stimulant laxatives at recommended doses are harmful to the colon or cause patients to become dependent on them to achieve satisfactory bowel function.⁶²

Chloride Channel Opener. Lubiprostone, a novel chloride channel opener, was recently approved by the Food and Drug Administration (FDA) for chronic constipation; however, its role in C-IBS is currently not known.⁶³

Antidepressants. The efficacy of tricylic antidepressants (TCAs) in IBS remains in question. A meta-analysis published in 2000 of 11 randomized, double-blind, placebo-controlled trials concluded that antidepressants are effective in reducing the overall symptoms associated with IBS and other functional gastrointestinal disorders in about one third of patients (odds ratio for symptom reduction, 4.2 [95% confidence interval, 2.3-7.9]) and abdominal pain.⁵¹ A Cochrane meta-analysis, which included only 6 randomized, double-blind, placebo-controlled studies of antidepressants due to concerns about methodological weaknesses in nonincluded trials, found no improvement⁵² with TCAs in IBS. A large multicenter trial in women with moderate to severe functional bowel disorders showed no significant improvement in the intention-to-treat analysis (60% vs 47%; P = .16) but showed significant benefit in the per-protocol analysis (73% vs 49%; P = .01).⁶⁴ Although clinical experience suggests that selective serotonin reuptake inhibitors may have efficacy, they have not been well studied in randomized placebo-controlled trials.⁶⁵ A recent small study found improvement in abdominal pain, bloating, and overall well-being but only modest effects on stool pattern.⁵³

If a trial of TCA treatment is performed, the daily dosage used in IBS is generally lower than that required for antidepressant effects.⁶⁶ Secondary amine TCAs (nortriptyline, desipramine) are better tolerated by many patients than parent tertiary amines (amitriptyline, imipramine, doxepin) because of fewer anticholinergic, sedating antihistaminic, and α-adrenergic adverse effects. Constipation can be exacerbated in patients receiving higher doses of TCAs and therefore, if these medications are going to be used in C-IBS, close monitoring of bowel function is warranted.⁶⁷

Tegaserod. Mrs G arrived asking for tegaserod for the treatment of her symptoms. Tegaserod is a selective serotonin receptor type-4 (5-HT₄) partial agonist that has received FDA approval for treatment of women with C-IBS and for men and women younger than 65 years with chronic constipation. It has prokinetic, antinociceptive, and secretory effects on the gastrointestinal tract.⁶⁸ Tegaserod has been evaluated in several large, multicenter, randomized, placebo-controlled trials^{54 - 55 ,69 - 70} in patients with C-IBS. In these trials, patients with C-IBS received placebo or tegaserod (2 or 6 mg twice daily) for 12 weeks. The therapeutic gain, or improvement over placebo, for global relief of IBS symptoms in these studies has been relatively small, ranging from 5%⁵⁴ to 19% (eg, 62% for the tegaserod group vs 44% for placebo over weeks 1-12⁵⁵ ). Repeated treatment with tegaserod appears to have similar efficacy.⁷¹ Based on a systematic review of trials, the number needed to treat with tegaserod to improve one patient's symptoms is 14 for 6 mg twice daily and 20 for 2 mg twice daily.⁷² In general, tegaserod significantly improved bloating and abdominal discomfort and improved satisfaction with bowel habits, although the magnitude varied across trials due to the use of different scales used to measure individual symptoms.⁵⁷ These studies were predominantly conducted in women and therefore the effectiveness of tegaserod in men with C-IBS remains unclear.

The most common adverse reaction to tegaserod in clinical trials was diarrhea, occurring in approximately 9% of patients treated with tegaserod (6 mg twice daily) vs 4% of patients treated with placebo. Diarrhea occurred most commonly in the first week of the study, and fewer than 2% of patients withdrew from the studies because of diarrhea.⁵⁶ Although usually self-limited, severe diarrhea resulting in serious consequences (such as hypovolemia, hypotension, and syncope) has been reported, resulting in a 2004 update to the product labeling of tegaserod.

No episodes of ischemic colitis were reported in the clinical trials with tegaserod; however, ischemic colitis has been associated with tegaserod in postmarketing surveillance.⁷³ The clinical significance of these reports remains unclear, as the rate of occurrence of ischemic colitis in patients taking tegaserod has been calculated to be lower than the predicted rate of ischemic colitis in the general IBS population.⁷⁴

Tegaserod inhibits cytochrome P450 1A2 and 2D6 in human liver microsomes in vitro, but no significant cardiac effects (eg, prolongation of the QTc interval)⁷⁵ or drug interactions have been reported.

Tegaserod should not be used in patients with either severe renal impairment or moderate or severe hepatic impairment.⁶⁸ Although initial clinical trials suggested a slight increase in abdominal surgeries, particularly cholecystectomies, in patients receiving tegaserod compared with placebo (9/2965 [0.3%] vs 3/1740 [0.2%], respectively), an independent review of the surgeries suggested that they were unrelated to use of the study medication.⁷⁶ Likewise, subsequent studies have not shown an increase in surgeries.⁷⁶

Although not applicable to Mrs G, tegaserod is classified as “pregnancy category B” as no adequate, well-controlled studies have been undertaken in pregnant women. Therefore, tegaserod is not recommended during pregnancy or while breastfeeding.

To date no long-term safety issues have been associated with tegaserod, but few data are available. In a multicenter, open-label clinical trial, 304 patients with C-IBS were followed up for 1 year.⁷⁷ Adverse effects reported in this study were similar to those reported in the 3-month clinical trials. Tegaserod has been approved by the FDA for treatment of C-IBS for 4 to 6 weeks; patients responding may continue tegaserod for an additional 4 to 6 weeks.

Behavioral Therapy. Although psychological or psychiatric pathology does not cause IBS, psychosocial factors such as stress are associated with IBS, and these comorbid states will exacerbate IBS symptoms or impair the person's ability to cope with them.⁷⁸ Therefore, some patients, especially those with longstanding refractory symptoms, who have coexisting psychiatric abnormalities (such as anxiety, depression, major life stressors [including abuse], panic attacks, somatization disorders, and agoraphobia) may benefit from behavioral therapy. The American College of Gastroenterology Task Force has concluded that behavioral therapy, including psychotherapy, supportive listening, self-help groups, hypnotherapy, cognitive behavioral therapy, and biofeedback, is more effective than placebo at relieving individual symptoms of IBS.⁵⁷ Mrs G reports her stress level has had some influence on her symptoms and she could consider behavioral therapy to help her symptoms.

Complementary and Alternative Medicine. Mrs G does not mention trying any alternative therapies for treatment of her symptoms. However, complementary and alternative medicine is used by more than one quarter of patients with gastrointestinal disorders, although few studies have defined its efficacy.⁷⁹ A well-conducted double-blind randomized trial compared a “standard” Chinese herbal formulation consisting of 20 different herbal medications with an individualized formulation that consisted of a combination of up to 81 Chinese herbs and to placebo.⁸⁰ In this study, patients in the individual and standard Chinese herbal medicine groups reported significant improvement in bowel symptoms over placebo (76% vs 64% vs 33%, respectively; P = .007). Although no significant adverse effects were reported, Chinese herbal medicines have been associated with a number of adverse effects including drug-induced hepatitis.⁸¹ Controlled trials comparing traditional Chinese acupuncture with sham needle insertion have shown conflicting results.^{82 - 84} Finally, ayurvedic herbal medicine (AHM) has been studied in a randomized double-blind trial comparing “standard therapy” with AHM and to placebo in 169 patients.⁸⁵ Sixty-four percent of patients receiving AHM reported improvement in symptoms, compared with only 32% of patients receiving placebo. For patients with pain-predominant IBS, however, standard therapy was more effective. Finally, a meta-analysis of randomized controlled trials using peppermint oil was inconclusive about its efficacy in IBS.⁸⁶

Since 1997, when the FDA relaxed previous regulations on direct-to-consumer advertising (DTCA), spending on DTCA for prescription drugs in the United States has increased dramatically, reaching $2.7 billion in 2001.⁸⁷ This rapid rise in DTCA has raised concerns that it may be having untoward effects such as interfering with the patient-physician relationship, increasing medical costs, providing misleading information, and potentially endangering health, especially for non–life-threatening illnesses or “lifestyle medications” for which the risk-benefit ratio remains unclear. Proponents for DTCA, however, argue that DTCA enhances the patient-physician relationship by educating patients, especially individuals with limited resources. Proponents also argue that DTCA improves health and reduces medical costs by earlier detection of disease and increased productivity. One study found that standardized patients requesting a specific antidepressant were significantly more likely to be prescribed an antidepressant whether or not they had symptoms consistent with depression.⁸⁸

In my own clinical practice, I believe DTCA has resulted in an increased awareness of gastrointestinal diseases such as gastroesophageal reflux, IBS, hepatitis, and colon cancer. In the case of Mrs G, DTCA made her aware of a new treatment option for C-IBS and initiated a discussion regarding the benefits and potential risks of tegaserod for her symptoms. Mrs G already had a healthy lifestyle with a diet high in fiber and had inadequate response to most laxatives; therefore I believe a trial with tegaserod was a reasonable option for her.

Mrs G has had a good response to tegaserod; therefore, based on the available trial data, I recommend that she continue tegaserod for approximately 4 to 6 weeks total and then discontinue it. If her symptoms recur, then she should resume tegaserod for another 6 weeks. If she is unable to discontinue the medication due to recurrence of symptoms, then a trial at a lower or intermittent dose could be attempted. She may benefit from behavioral therapy to help reduce stress levels. If necessary, another option would be a trial of PEG or a TCA, with careful monitoring of her bowel function.

QUESTION: The evidence from the studies of tegaserod (and I believe that all of the studies have been funded by the manufacturer) suggests that improvement in symptoms from treatment with this drug is small. If Mrs G hadn't requested a specific medication, what would your first medication choice have been, if any, for her?

DR LEMBO: Mrs G had already tried most over-the-counter laxatives, including stool softeners and osmotic and stimulant laxatives, which had given her inadequate or only temporary relief of her C-IBS symptoms. Therefore, the medications that I considered for her were tegaserod and PEG. Tegaserod has been shown to be effective, even if only modestly, in C-IBS and chronic constipation. PEG, in contrast, has only been studied in patients with constipation for relatively short duration (ie, 2 weeks). Therefore, its effectiveness in reducing abdominal pain and discomfort associated with C-IBS is unknown, although in my own practice I find it effective in some patients.^{50 ,89}

QUESTION: The response to placebo that you showed, which is a 50% improvement, is about twice the usual response to placebo with other kinds of pain. Have there been any studies of a blind crossover between placebo and tegaserod? And in those patients who have failed treatment with placebo, about half of them, is there any response to the substitution of another placebo?

DR LEMBO: Studies of IBS have shown a high placebo response rate, which has been a difficult hurdle to overcome in clinical trials. The average placebo response in clinical trials with IBS is approximately 40%.⁶⁸ This effect is likely to be a combination of the subjective measures used to assess response, the frequency of medications, the strength of the patient-physician interaction, and the overall treatment effect.⁹⁰ The placebo response in the tegaserod trials are in line with the placebo response seen in other IBS trials. I’m not aware of any crossover trials with tegaserod or retreatment with a second placebo after initially failed treatment with placebo.

QUESTION: Many of our elderly patients have symptoms that sound like IBS, yet they fail most of the usual treatments. Is there any experience with tegaserod in the elderly, those in their 70s and 80s?

DR LEMBO: Elderly patients with new or recent change in IBS symptoms should be thoroughly evaluated prior to attributing the symptoms to IBS. For C-IBS, tegaserod appears to be equally effective in young and elderly patients, and no dose adjustment is necessary.^{54 ,91} In contrast, tegaserod was not effective in elderly patients with chronic constipation^{92 - 93} and therefore is not recommended for patients with chronic constipation over the age of 65.