464 A Placebo-Controlled Study of Clonidine on Symptoms in Women With Fecal Incontinence

Abstract

Abnormalities in rectal compliance have been identified in irritable bowel syndrome (IBS), wherein patients exhibit decreased rectal compliance in response to experimental distention (Kwan CL, et al. Neurogastroenterol Motil 2004; Shroff S, et al. DDW 2012). However, these differences in rectal physiology are not uniformly present in all IBS subjects. We sought to examine whether psychiatric comorbidity (e.g., depression, anxiety) in IBS has mechanistic relevance to rectal compliance. We hypothesized that dysregulation of autonomic tone inherent in mood disorders leads to decreased rectal compliance in IBS patients. Methods: 38 female subjects (43.6 ±11.1 yrs; 22 Rome III IBS/16 healthy controls) were recruited. Measures of mood (Beck Depression and Anxiety Inventories, [BDI, BAI]) and somatization (Patient Health Questionnaire [PHQ-15]) were collected. Both groups underwent 4 series of 6 pseudo-randomized, barostat-controlled rectal distentions using either high pressure (HPD, 50 mmHg) or low pressure (LPD, 25 mmHg) delivery. Dynamic rectal compliances (ΔV/ΔP) were derived from the ascending phase of the distention. Multivariate linear regression was employed to determine whether psychiatric comorbidity independently influenced rectal compliance. Results: Dynamic rectal compliance was significantly lower in IBS vs. controls for both LPD (8.1±1.8 vs. 9.4±1.6 ml/mmHg; p=0.03) and HPD (6.0±1.1 vs. 7.0±1.1 ml/mmHg; p =0.01). High ratings in anxiety (BAI≥16), depression (BDI≥14) and somatization (PHQ-15≥15) were identified in 31.8%, 40.9%, and 50.0% of IBS subjects, respectively. In high anxiety subjects, rectal compliance was significantly diminished with HPD (5.6±0.8 vs. 6.7±1.1 ml/mmHg; p =0.008), and trended lower during LPD (7.9±1.5 vs. 8.8±1.8 ml/ mmHg, P=0.18). High depression scores were also associated with decreased rectal compliance with HPD (5.6±1.0 vs. 6.8±1.2, p=0.02) and trended toward lower compliance during LPD (8.1±1.5 vs. 8.8±1.8 ml/mmHg, P=0.2). In contrast, degree of somatization did not influence rectal compliance with either distention stimulus (P.0.20 for each). Multivariate analyses suggested the effects of anxiety on rectal compliance were independent of IBS during HPD (B=-0.04, p=0.06), but not LPD (B=-0.008, p=0.8). Depression and somatization had no effect on rectal compliance independent of IBS at either pressure level (p .0.15 for each).Conclusions: Decreased dynamic rectal compliance is observed in IBS with both low pressure and high pressure rectal distensions. Mood symptoms common to IBS also are associated with diminished rectal compliance, particularly withmore noxious stimuli. Anxiety appears to influence rectal compliance independent of the functional GI diagnosis itself, an effect potentially mediated by sympathetic autonomic regulation of intestinal motor function.