Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease.

PURPOSE: Fluvoxamine (FVX) is metabolized by cytochrome P450 (CYP) 2D6 and CYP1A2 and inhibits CYP3A4. The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). METHODS: Blood samples were taken from 49 depressive patients to determine plasma concentration of FVX, ALP or both. Twenty-four samples were taken during the FVX-alone period, 21 samples during the ALP-alone period and 30 samples during the FVX-ALP period. Subjects were also genotyped for CYP2D6. RESULTS: The concentration-to-dose (C/D) ratio of ALP during the FVX-treatment period was significantly higher than that during the ALP-alone period. The CYP2D6 genotype affected neither the C/D ratios of FVX nor the extent of interaction. The mean C/D ratio of FVX in smokers was reduced by more than 30% in comparison with that in non-smokers. The mean C/D ratio of ALP in non-smokers was increased by FVX, while that in smokers was unchanged. CONCLUSIONS: The extent of interaction between FVX and ALP may be affected by smoking, which alters the C/D ratio of FVX. Therefore, when FVX and ALP are concomitantly administered, it should be noted that non-smokers may exhibit greater drug interaction than smokers.

High prevalence of irritable bowel syndrome in medical outpatients in Japan.

BACKGROUND AND GOALS: The prevalence of irritable bowel syndrome (IBS) among Japanese patients who visit hospitals departments of internal medicine is thought to be high. However, no clear statistical evidence has been provided to support such a claim. We tested the hypotheses that the prevalence of IBS in medical outpatients clinics in Japan is high, and that IBS patients feel more psychosocial stress than patients without IBS. STUDY: The subjects in this study were 633 patients who visited participating physicians. Patients were asked to fill in the Japanese version of the Rome II Modular Questionnaire (RIIMQ) for IBS diagnosis, the Self-reported Irritable Bowel Syndrome Questionnaire (SIBSQ) for severity of the disease and the demographic questionnaire for perceived stress and life style. RESULTS: Rome II-defined IBS was diagnosed in 196 patients (31%). Analysis of variance revealed significant difference in the IBS scores of SIBSQ among IBS subjects (39.0+/-11.1, mean+/-SD), functional bowel disorder subjects (27.1+/-10.2), and normal subjects (24.0+/-10.0, P<0.01). The prevalence of IBS depending on age formed 2 peaks, one among adolescents and the other among the elderly. IBS patients had significantly more perceived stress (P<0.0001), irregular sleep habit (P<0.0001), and irregular meal habit (P<0.0001) than those without IBS. CONCLUSIONS: The prevalence of IBS among medical outpatients in Japan is high (31%). IBS subjects among medically ill patients are thought to have more perceived stress and less regular life styles.

Childhood physical abuse in outpatients with psychosomatic symptoms.

BACKGROUND: In Japan and Asia, few studies have been done of physical and sexual abuse. This study was aimed to determine whether a history of childhood physical abuse is associated with anxiety, depression and self-injurious behavior in outpatients with psychosomatic symptoms. METHODS: We divided 564 consecutive new outpatients at the Department of Psychosomatic Medicine of Kyushu University Hospital into two groups: a physically abused group and a non-abused group. Psychological test scores and the prevalence of self-injurious behavior were compared between the two groups. RESULTS: A history of childhood physical abuse was reported by patients with depressive disorders(12.7%), anxiety disorders(16.7%), eating disorders (16.3%), pain disorders (10.8%), irritable bowel syndrome (12.5%), and functional dyspepsia(7.5%). In both the patients with depressive disorders and those with anxiety disorders, STAI-I (state anxiety) and STAI-II (trait anxiety) were higher in the abused group than in the non-abused group (p < 0.05).In the patients with depressive disorders, the abused group was younger than the non-abused group (p < 0.05). The prevalence of self-injurious behavior of the patients with depressive disorders, anxiety disorders and pain disorders was higher in the abused groups than in the non-abused groups (p < 0.005). CONCLUSION: A history of childhood physical abuse is associated with psychological distress such as anxiety, depression and self-injurious behavior in outpatients with psychosomatic symptoms. It is important for physicians to consider the history of abuse in the primary care of these patients.

[Psychosomatic approach for IBS patients].

Psychosomatic medical treatment is not a treatment that only specialists can do. On psychosomatic approach for IBS patients, it is important to understand not only IBS symptoms but also IBS patients themselves and their psychosocial factors. Not a few serious IBS patients have aspects of anxiety and depression. It needs psychosomatic approach that combined with drugs and simple psychotherapy to treat them. In treating IBS patients, we should first consider not only organic or functional mechanism of their symptoms but also the psychosocial meaning of them.

Edrophonium provocative testing for the evaluation of upper gastrointestinal hypersensitivity in patients with nonulcer dyspepsia.

The aim of this study was to examine if edrophonium provocative testing is useful for evaluating upper gastrointestinal hypersensitivity in patients with nonulcer dyspepsia (NUD). A questionnaire rating dyspeptic symptoms was done for 58 patients with NUD. The patients were then given an intravenous infusion of saline followed by 5 mg of edrophonium. Baseline esophageal manometry was also done. Patients whose usual symptoms were reproduced (48.3%) had significantly higher symptom scores (13.0 [8.5, 17.0] vs. 8.5 [6.0, 11.0]; P = 0.015) and a significantly higher number of symptoms (4.0 [2.5, 6.0] vs. 3.0 [1.0, 4.0]; P = 0.010) than patients whose usual symptoms were not reproduced. The presence of an esophageal motility disorder was not significantly different between the two groups. These findings suggest upper gastrointestinal hypersensitivity in the patients whose symptoms were reproduced. Edrophonium provocative testing might be useful for evaluating upper gastrointestinal hypersensitivity in patients with NUD.

What does pain or discomfort in irritable bowel syndrome mean?

Despite many studies on pain of functional gastrointestinal disorders (FGID), the pain mechanism of FGID is not well understood, and pain treatment of FGID is not established. Following our former functional dyspepsia (FD) study, we proposed two subgroups of patients with irritable bowel syndrome (IBS), pain and discomfort (not pain). The duration of disease of discomfort IBS patients was longer than that of pain IBS patients (P < 0.05) The rate of anxiety disorder of pain IBS patients tended to be higher than that of discomfort IBS patients (P = 0.07172). Fifteen (15.2%) of 99 pain IBS patients and 1 (3.4%) of 29 discomfort IBS patients overlapped FD (P < 0.1). We expected that a common psychosocial mechanism would influence both pain dyspepsia patients and pain IBS patients, however, there were some differences between these FGID patients with pain. Anxiety in IBS patients with lower gastrointestinal pain seems to be important in their treatment.

Comparison of the esophageal manometric characteristics of idiopathic and reflux-associated esophageal spasm: evaluation by 24-hour ambulatory esophageal motility and pH monitoring.

Diffuse esophageal spasm (DES) is a typical esophageal dysfunction, but its cause is unknown. DES has been classified into reflux-associated esophageal spasm (RDES), caused by acid exposure, and idiopathic esophageal spasm (IDES), of unknown causes. The differences in esophageal motility pattern between the RDES and IDES are clues to elucidating the pathogenesis of DES. Although 24-hr ambulatory esophageal motility and pH monitoring is considered a feasible method for evaluating gastroesophageal reflux and esophageal function, most researchers previously defined the RDES as DES accompanied by esophagitis and heartburn using standard manometry over a short time frame. To clarify the pathogenesis of RDES, we did this research using 24-hr ambulatory esophageal motility and pH monitoring. The investigation included 25 normal controls and 116 patients with upper digestive symptoms. Among the 116 patients, 45 had DES (11 RDES, 30 IDES, and DES-GERD coexistence). Patients with RDES showed a significantly higher frequency of simultaneous contractions than did patients with IDES. Heartburn has been said to be peculiar to RDES, but also occurred in 12.5% of IDES. No significant differences in the mean pH of the esophagus during acid reflux were found between the RDES and IDES patients. Based on the results, we have proposed a refined definition of RDES.