The mass production of penicillin in the nineteen forties heralded a revolution in medicine. Not only could infections be cured but protection from the risks of infection allowed permitted critical advances in surgery and chemotherapy to occur. Moreover, the success of antibiotics encouraged the production of a range of new pharmacological substances that could treat most acute and chronic ailments. By the nineteen sixties, there was a pill for every ill (and for a number of situations that were not illnesses). The pharmacological bonanza continued throughout the latter half of the 20th century, but more recently drug development has begun to slow down. Fewer new drugs are being developed to treat infections or other acute diseases. Instead drug companies have decided that it is more profitable to develop maintenance drugs that people can take every day to treat or prevent long term conditions, such as high blood pressure, diabetes, arthritis, high blood cholesterol, prostatic cancer and irritable bowel syndrome.
Yes, IBS continues to be a major target for drug development. There are no fewer than 50 different drugs available to treat IBS. They include antispasmodics for abdominal pain, anti-motility agents and bile acid sequestrants for diarrhoea, laxatives, fibre and prokinetic agents for constipation, anti-flatulents for bloating and antidepressants and serotonin blockers for general symptoms of well being. Nearly all of these are supported by state-of-the-art, randomised double-blind, placebo-controlled trials, but are they useful? Do they work well enough in clinical practice?
The studies of efficacy always look good during the development phase of any new drug; otherwise it would never be approved. But few studies are done once a drug is approved and on the open market. Why would drug companies wish to test a drug that is selling well? The results of post marketing trials are never as good as the ‘phase 2’ studies conducted before the drug is released. Regression to the mean implies that as more studies are conducted the results diminish until they become similar to baseline. So does that indicate that the original studies were flawed? Not entirely, though it can be very difficult to prove that any drug is effective in IBS.
A major reason for this is the strength of ‘the placebo effect’ in IBS, which can be as high as 50% for abdominal pain. The discomfort and worry can make people very suggestible. This, in theory, can be accommodated by properly conducted double-blind, randomised, placebo-controlled trials. The difficulty is that in practice, such trials are not entirely ‘blind’. When the patients, recruited for trials of antidepressants were asked, they could usually tell whether they were taking the active drug or the placebo, thus negating any conclusion about efficacy. If that occurs for antidepressants, then it is likely to occur for the psychological end points of pain and quality of life in therapeutic trails in IBS, but to my knowledge, the question has never been asked in those trials.
Diarrhoea and constipation can be measured and so the physiological effect of drugs for bowel habit can be assessed in much the same way as those used to treat high blood pressure. Loperamide (Imodium) certainly reduces stool output while bisocodyl, senna and linaclotide increase it, but do these effects necessarily make people feel better. Many patients complain of an increase in pain and bloating associated with loperamide that is so great they stop taking it. The same can apply to bile acid sequestrants such as Questran, though I have found that the fact that patients can learn to titrate the dose gives them more control over their symptoms and more compliance. Laxatives and other drugs for constipation all stimulate bowel contractions, which can also tend to be unacceptably painful in patients with sensitive guts. Antidepressants might seem to offer a more global reduction in symptoms, but patients often complain of feeling somehow disconnected from reality and ‘spaced out’. All drugs have unwanted side effects and people with IBS are often as hypersensitive to these as they are to food or life events.
In the United States, courses of the poorly absorbed, broad-spectrum antibiotic, Rifaximin, are often prescribed to treat IBS on the assumption that many patients have Small Intestinal Bacterial Overgrowth (SIBO). Suffice to say that the assumption that SIBO is a major cause of IBS is contraversial and may be based on a misinterpretation of breath tests, while Rifaximin may reduce symptoms of IBS in the short term by depleting colonic bacteria and restricting fermentation, with long term consequences for intestinal sensitivity. So would short term gains result in long term pains? For more information, see my recent post on Small Intestinal Bacterial Overgrowth.
So are drugs helpful for IBS? After what seems like a lifetime in advising people with IBS, I think that although antispasmodics, anti-diarrhoeal agents or laxatives/prokinetic agents may be good to have on hand to help to relieve a flare up of symptoms, in the long term they can be disappointing and either have little effect or give rise to unwanted side effects. Medications can be habit forming; something the drug companies rely on. Many people continue to take their favourite drugs for IBS, not because they get any real symptom relief, but as a psychological prop because they fear an exacerbation of their symptoms if they stopp taking the medication. Most drugs for IBS act on cell membrane receptors, which either block cellular mechanisms inducing sensitivity, motility or secretion or (in the case of constipation) trigger these. If you suddenly stop taking a drug that is blocking a key receptor, the physiological effects are released from inhibition and control and you may well experience a rebound in symptoms. It is always a good idea to tail off a drug you no longer need or to take it intermittently when you have a flare up.
At present, there is no drug that cures IBS, nor any that suppresses it long term without the risk of unwanted and unacceptable side effects. There are, however, some medications that may be useful in the short term suppression of acute flare-ups, but these need to be taken sparingly and tailed off when no longer required.
Do write in and tell me if there are any drugs that you find helpful for your IBS?