Gene/Protein Disease Symptom Drug Enzyme Compound
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This article reviews briefly the evidence to support current therapies in irritable bowel syndrome (IBS) and the novel therapeutic approaches on the threshold of clinical application. Fiber is indicated at a dose of at least 12 grams per day in patients with constipation-predominant IBS. Loperamide (and probably other opioid agonists) are of proven benefit in diarrhea-predominant IBS; loperamide may also aid continence by enhancing resting anal tone, but there is no evidence that it results in pain relief. In general, smooth muscle relaxants are best used sparingly, on an as-needed basis, because their overall efficacy is unclear. The 5-HT3 antagonist, alosetron, results in adequate relief of pain and improvements in bowel function in female nonconstipated patients with IBS. Psychotropic agents are important in relieving depression and are of proven benefit for pain and diarrhea in patients with depression associated with IBS. Further trials with selective serotonin reuptake inhibitors are awaited. Psychological treatments including hypnotherapy are less widely available but may play an important role in the relief of pain. In summary, current therapies targeted on the predominant symptoms in IBS are moderately successful. As the bowel sensorimotor and limbic system disturbances of IBS are more clearly understood, we should anticipate other pharmacologic approaches in the near future, including alpha-adrenergic agonists and 5-HT4 agonists. New therapies directed at treatment of the syndrome, rather than relief of symptoms, are needed.
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PMID:Therapeutic approach to the patient with irritable bowel syndrome. 1058 70

This report highlights various considerations regarding the potential effects of concurrent psychiatric conditions and a history of abuse in patient volunteers for clinical trials in irritable bowel syndrome (IBS). Even though many studies have used psychological rating scales to assess personality and psychological traits of patients with IBS, the prevalence of the different psychiatric diagnoses (i.e., categorical assessment) in patients with IBS has only recently been assessed systematically. Recent studies of treatment-seeking patients have indicated that the majority of individuals (50% to 90%) who seek treatment for IBS have a lifetime history or currently have one or more common psychiatric conditions: major depressive disorder, generalized anxiety disorder, panic disorder, social phobia, somatization disorder, and posttraumatic stress disorder. Traditional clinical wisdom is that the presence of a psychiatric disorder increases the likelihood that an IBS patient will seek treatment. However, recent data suggest that IBS and psychiatric disorders are associated regardless of treatment-seeking status. Patients with psychiatric disorders should be included in clinical IBS studies, because this reflects the actual patient population. Extrapolating from the psychiatric literature, inclusion of patients with IBS with mild to moderate anxiety or depression is warranted.
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PMID:Experience with anxiety and depression treatment studies: implications for designing irritable bowel syndrome clinical trials. 1058 75

Fructose and lactose malabsorption are characterized by impaired duodenal fructose transport or by the deficiency of mucosal lactase, respectively. As a consequence, the nonabsorbed saccharides reach the colon, where they are broken down by bacteria to short fatty acids, CO2, and H2. Bloating, cramps, osmotic diarrhea, and other symptoms of irritable bowel syndrome are the consequence and can be seen in about 50% of carbohydrate malabsorbers. We have previously shown that fructose as well as lactose malabsorption were associated with signs of mental depression. It was therefore of interest to investigate possible interactions between fructose and lactose malabsorption and their influence on the development of signs of depression. In all, 111 otherwise healthy volunteers (81 females and 30 males) with gastrointestinal complaints were analyzed by measuring breath H2 concentrations after an oral dose of 50 g lactose and of 50 g fructose one week apart. They were classified as normals, isolated fructose malabsorbers, isolated lactose malabsorbers, and combined fructose/lactose malabsorbers. All patients filled out a Beck's depression inventory-questionnaire. Twenty-five individuals (22.5%) were neither fructose nor lactose malabsorbers (group 1), 69 (62.2%) were only fructose malabsorbers (group 2), 4 (3.6%) were only lactose malabsorbers (group 3), and 13 (11.7%) presented with fructose and lactose malabsorption together (group 4). Isolated fructose malabsorption and combined fructose/lactose malabsorption was significantly associated with a higher Beck's depression score. Further analysis of the data show that this association was strong in females (P < 0.01), but there was no such association between carbohydrate malabsorption and early signs of depression in males. In conclusion, the data confirm that fructose malabsorption may play a role in the development of mental depression in females and additional lactose malabsorption seems to further increase the risk for development of mental depression.
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PMID:Carbohydrate malabsorption syndromes and early signs of mental depression in females. 1096

A blind placebo-controlled randomized trial was made of efficiency and safety of sulpirid compared to basic treatment in irritable colon syndrome (ICS). 40 patients over 18 years with ICS were randomized into two groups. Group 1 patients received sulpirid monotherapy (200-450 mg/day). Group 2 received basic therapy (combined treatment with spasmolytic, bacterial and cholagogic drugs). The treatment took 6 weeks. It was proved that sulpirid is more effective in ICS as it reduced the syndrome by 85% (basic therapy by 10%), relieved abdominalgia, anxiety, depression, corrected stool. As to disbacteriosis, sulpirid effect was weak. Tolerance of treatment in both groups was good. Side effects developed in 15% of group 1 patients and were easily corrected by lowering of the daily dose.
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PMID:[Sulpiride treatment of irritable colon syndrome]. 1097 37

Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins have been implicated in the pathophysiology, diagnosis, and treatment of mood disorders and proposed as a state-dependent biochemical mood marker in mononuclear leukocytes. Irritable bowel syndrome (IBS) is associated with changes in mood, affecting patients' illness perceptions and behavior. We examined whether mononuclear leukocytes of patients with IBS have altered G protein measures. We undertook G protein functional measurements through agonist-enhanced [3H]Gpp(NH)p binding capacity and quantitative measures by immunoblot analysis using anti-Galpha antibodies in mononuclear leukocytes obtained from 19 IBS patients (Rome criteria) and 19 healthy matched subjects. The study groups were similar in age, gender, and years of education. Mononuclear leukocyte functions of G(s) (21.3+/-8.3%) and G(i) (22.2+/-6.7%) proteins in IBS patients were similar to healthy subjects (24.8+/-4.7 and 25.2+/-4.0%, respectively). The relative immunoreactivities of the G(sa) (98.9+/-10.2%) and the G(ia) (104.2+/-11.5%) subunit proteins in mononuclear leukocytes of IBS patients were also similar to those in healthy subjects. Two patients clinically diagnosed as depressed were detected by the G protein assay. The results lend objective support to the contention that major depression is not a causative factor in IBS, nor associated with its severity. The G protein assay may provide an objective biochemical tool for detecting depression in IBS, differentiating it from psychological distress that is commonly diagnosed by subjective tests.
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PMID:G protein levels and function as an objective measure of depression in patients with functional bowel disorders. 1100 21

I believe there are four essential elements in the management of patients with irritable bowel syndrome (IBS): to establish a good physician-patient relationship; to educate patients about their condition; to emphasize the excellent prognosis and benign nature of the illness; and to employ therapeutic interventions centering on dietary modifications, pharmacotherapy, and behavioral strategies tailored to the individual. Initially, I establish the diagnosis, exclude organic causes, educate patients about the disease, establish realistic expectations and consistent limits, and involve patients in disease management. I find it critical to determine why the patient is seeking assistance (eg, cancer phobia, disability, interpersonal distress, or exacerbation of symptoms). Most patients can be treated by their primary care physician. However, specialty consultations may be needed to reinforce management strategies, perform additional diagnostic tests, or institute specialized treatment. Psychological co-morbidities do not cause symptoms but do affect how patients respond to them and influence health care-seeking behavior. I find that these issues are best explored over a series of visits when the physician-patient relationship has been established. It can be helpful to have patients fill out a self-administered test to identify psychological co-morbidities. I often use these tests as a basis for extended inquiries into this area, resulting in the initiation of appropriate therapies. I encourage patients to keep a 2-week diary of food intake and gastrointestinal symptoms. In this way, patients become actively involved in management of their disease, and I may be able to obtain information from the diary that will be valuable in making treatment decisions. I do not believe that diagnostic studies for food intolerances are cost-effective or particularly helpful; however, exclusion diets may be beneficial. I introduce fiber supplements gradually and monitor them for tolerance and palatability. Synthetic fiber is often better-tolerated than natural fiber, but must be individualized. In my experience, excessive fiber supplementation often is counterproductive, as abdominal cramps and bloating may worsen. Antidiarrheal agents are very effective when used correctly, preferably in divided doses. I use them in patients in anticipation of diarrhea and especially in those who fear symptoms when engaged in activities outside the home. I encourage patients to make decisions as to when and how much to use. However, almost always, a morning dose before breakfast is used (loperamide, 2 to 6 mg) and, perhaps again later in the day when symptoms of diarrhea are prominent. I prefer antispasmodics to be used intermittently in response to periods of increased abdominal pain, cramps, and urgency. For patients with daily symptoms, especially after meals, agents such as dicyclomine before meals are useful. For patients with infrequent but severe episodes of unpredictable pain, sublingual hyoscyamine often produces rapid relief and instills confidence. In general, I recommend that oral antispasmodics be used for a limited period of time rather than indefinitely, and generally for periods of time when symptoms are prominent. For chronic visceral pain syndromes, I recommend small doses of tricyclic antidepressants. These agents are especially effective in diarrhea-predominant patients with disturbed sleep patterns but may be unacceptable to patients with constipation. I educate patients that side effects occur early and benefits may not be apparent for 3 to 4 weeks. I consider using SSRIs in low doses in patients with constipation-predominant IBS; cisapride, 10 to 20 mg three times per day, also may be beneficial. When taken with drugs that inhibit cytochrome P450, cisapride has been associated with serious cardiac arrhythmias caused by QT prolongation, including ventricular arrhythmias and torsades de pointes. These drugs include the azole fungicides; erythromycin, clarithromycin, and troleandomycin; some antidepressants; HIV protease inhibitors; and others. In patients with IBS with mild to moderate co-morbid depression, I have found that the use of SSRIs such as paroxetine, fluoxetine, or sertraline may be beneficial. It is important to tell patients that anxiety and disturbed sleep may occur during the first 10 days and benefits may not occur for 3 to 4 weeks. I prescribe a small amount of a short-acting benzodiazepine such as alprazolam, 0.5 mg two times per day, to control these symptoms. For generalized anxiety without depression, buspirone or clonazepam may be useful. I have found that patients who also have associated panic disorder may benefit from a benzodiazepine, tricyclic antidepressant, or an SSRI. However, these patients are best managed in conjunction with a psychiatrist or psychologist. I consider the use of alternative therapies in patients who fail to respond to conventional measures and who are receptive to alternative strategies. These include general relaxation techniques such as biofeedback and hypnosis therapies.
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PMID:Irritable Bowel Syndrome. 1109 67

Alterations of gastrointestinal (GI) motor function are part of the visceral responses to stress. Inhibition of gastric emptying and stimulation of colonic motor function are the commonly encountered patterns induced by various stressors. Activation of brain corticotropin-releasing factor (CRF) receptors mediates stress-related inhibition of upper GI and stimulation of lower GI motor function through interaction with different CRF receptor subtypes. CRF subtype 1 receptors are involved in the colonic and anxiogenic responses to stress and may have clinical relevance in the comorbidity of anxiety/depression and irritable bowel syndrome.
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PMID:Stress and the gastrointestinal tract III. Stress-related alterations of gut motor function: role of brain corticotropin-releasing factor receptors. 1120 37

Fibromyalgia syndrome (FMS), characterized by widespread pain and tenderness on palpation (tender points), is much more common in women than in men in a proportion of 9:1. Two recent studies have shown important gender differences in various clinical characteristics of FMS. In a community and a clinic sample, women experienced significantly more common fatigue, morning fatigue, hurt all over, total number of symptoms, and irritable bowel syndrome. Women had significantly more tender points. Pain severity, global severity and physical functioning were not significantly different between the sexes, nor were psychologic factors, eg, anxiety, stress, and depression. Gender differences have also been observed in other related syndromes, eg, chronic fatigue syndrome, irritable bowel syndrome, and headaches. The mechanisms of gender differences in these illnesses are not fully understood, but are likely to involve an interaction between biology, psychology, and sociocultural factors.
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PMID:The role of gender in fibromyalgia syndrome. 1128 69

Although irritable bowel syndrome (IBS) can be considered a biopsychological disorder in which an association between life stress and physiological changes leading to bowel irregularity is present, there is a lack of data concerning possible modifications of the adrenal function during the disease. The aim of the present study was to measure biological and psychological variables related to the activity of the hypothalamo-pituitary-adrenal axis in IBS patients compared to healthy subjects. Cortisol was measured in the saliva (obtained by a stress-free, non invasive collection procedure) of 55 IBS outpatients and 28 matched controls. Moreover, each subject completed the following self-administered questionnaires: the Rome Burnout Inventory (RBI) in its physical (RBI-PE) and emotional-mental exhaustion (RBI-EME) components, Beck Depression Inventory, State and Trait Anxiety Inventory (STAI), Perceived Social Support Scale (PSSS) and a Scale for the Assessment of Perceived Actual Work-Non Work Stress. Compared with controls, IBS subjects showed significantly higher levels of cortisol in the morning and lower in the evening, while they maintained the physiological circadian fluctuation (i.e. cortisol morning level higher than in the evening). Moreover, IBS patients presented a significant difference from controls in RBI-PE scores, which confirms the presence of fatigue, a symptom frequently reported by the patients. Compared with controls, no differences were found in IBS patients with respect to other psychological parameters. These findings suggest a dysregulation of the adrenal activity in IBS patients. The results may be relevant considering that changes in cortisol levels have been shown to be sensitive indicators of psychosocial stress and coping patterns in both laboratory and life situations.
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PMID:Actual stress, psychopathology and salivary cortisol levels in the irritable bowel syndrome (IBS). 1131 46

Community studies have shown that stressful life events, psychological distress, and depressive and anxiety disorders are associated with 1) a range of medical symptoms without identified pathology, 2) increased health care utilization, and 3) increased costs. In both primary care and medical specialty samples, patients who have syndromes with ill-defined pathologic mechanisms (such as the irritable bowel syndrome and fibromyalgia) have been shown to have significantly higher rates of anxiety and depressive disorders than do patients with comparable, well-defined medical diseases and similar symptoms. Other studies show that after adjustment for severity of medical illness, patients with depression or anxiety and comorbid medical disease have significantly more medical symptoms without identified pathology than do patients with a similar medical disease alone. Both childhood maltreatment and psychological trauma in adulthood have been associated with increased vulnerability to psychiatric illness and more medical symptoms. The substantial functional impairment, distress, and costs associated with medical symptoms without identified pathology suggest that research studies promoting a better understanding of the biopsychosocial cause of these symptoms may yield pragmatic, cost-effective approaches to treatment in medical settings.
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PMID:Medical symptoms without identified pathology: relationship to psychiatric disorders, childhood and adult trauma, and personality traits. 1134 29


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