Benzodiazepines have been prescribed to treat anxiety contributing to and stemming from irritable bowel syndrome (IBS). Despite this, Farthing suggests that support for anxiolytics in the treatment of IBS has not been compelling enough to advocate their use. Farthing favors the use of antidepressants, which may treat two aspects of the syndrome, and with decreased potential for dependence. In contrast, Tollefson et al studied a short course of alprazolam and noted significant improvements in both anxiety and severity of IBS symptoms, leading them to recommend the medication’s use in acute disease.
Somatostatin analogues may mediate the symptoms of irritable bowel syndrome (IBS) via an analgesic effect for somatic and visceral pain, and an ability to alter the threshold to distention at the level of the rectum. Bradette et al showed a significant increase in postprandial but not fasting colonic tone following subcutaneous administration of octreotide 1.25 mcg/kg. Significant increases in mean distension pressures were required to produce abdominal discomfort or pain. The authors demonstrated a higher tolerance of visceral pain and discomfort in healthy volunteers as compared to IBS patients.
Cholecystokinin (CCK) Antagonists
CCK is a peptide released by endocrine cells in the small intestine in response to food intake; it functions as a neurotransmitter at the level of the myenteric ganglia, submucosal ganglia, and smooth muscle to stimulate colonic motor activity. Using healthy volunteers and irritable bowel syndrome (IBS) patients, Niederau et al tested the effects of loxiglumide, a specific cholecystokinin antagonist, on cerulein (a CCK analogue) and naturally occurring postprandial CCK following a 1,000-kCal meal.
Colonic motility was significantly increased in healthy subjects at the high dose (30 to 60 ng/kg) of cerulein and following the meal. In these subjects, loxiglumide did not affect postprandial motility, but did block the effects of exogenous stimulation. IBS patients had significant increases in colonic motility in response to food that was not significantly inhibited by loxiglumide.
Women tend to have exacerbations of irritable bowel syndrome (IBS) symptoms during the luteal phase of the menstrual cycle, during which progesterone is released. Progesterone, which exerts a relaxant effect on smooth muscle, may act as an intestinal antagonist and be responsible for these exacerbations. One approach may be to arrest ovulation and menstruation in select patients to attenuate these flares.
In a long-term, open-label phase of a follow-up trial, the leuprolide dose was changed.Dosages were started at 0.5 mg daily and titrated to 1.0 to 1.5 mg daily based on therapeutic effect and side effects. The results at the end of one year were a highly significant reduction in vomiting episodes and a continued, even more significant decrease in nausea, bloating, abdominal pain, early satiety, and anorexia. Placebo patients from a previous three-month study who were switched to this regimen for the remaining nine months of the trial also had significant reductions in these complaints.
At the trial’s end, both groups reported equally significant decreases in symptom scores. Adverse effects included bone pain and increased edema. Other potential adverse effects include headache, migraine, hot flashes, cystitis, hematuria, menorrhagia, and respiratory symptoms. The authors concluded that progesterone might contribute to symptoms of functional bowel disorders.