G. W. Libby

Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome

Background: Antidepressants are used in the treatment of irritable bowel syndrome but it is unclear whether any symptomatic improvement is due solely to correction of an associated affective disorder, or whether these drugs have effects on bowel function which may be of therapeutic benefit. Intestinal transit is known to be abnormal in some irritable bowel syndrome patients.

5-Hydroxytryptamine and human small intestinal motility: effect of inhibiting 5-hydroxytryptamine reuptake.

Parenteral 5-hydroxytryptamine stimulates small intestinal motility, but the effect of continuous stimulation with 5-hydroxytryptamine on the human migrating motor complex is unknown. Using a selective 5-hydroxytryptamine reuptake inhibitor, paroxetine, this study investigated the effect of indirect 5-hydroxytryptamine agonism on fasting small intestinal motility and transit. Eight healthy subjects were studied while receiving paroxetine 30 mg daily for five days and while receiving no treatment, in random order. Ambulant small intestinal motility was recorded from five sensors positioned from the duodenojejunal flexure to the ileum for 16-18 hours. Paroxetine reduced the migrating motor complex periodicity mean (SEM) from 81 (6) min to 67 (4) min (p < 0.05), and increased the propagation velocity of phase III from 3.1 to 4.7 cm/min in the proximal jejunum (p < 0.01), and from 1.6 to 3.4 cm/min distally (p < 0.001). Orocaecal transit time measured by lactulose hydrogen breath test was reduced by paroxetine from 70 (9) min to 48 (7) min (p < 0.05). These data suggest that 5-hydroxytryptamine participates in the control of migrating motor complexes in humans, and that selective 5-hydroxytryptamine reuptake inhibitors have a prokinetic action in the human small intestine.

Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome

Antidepressants are used in irritable bowel syndrome (IBS) and may have effects on the gut independent of improving mood. We have investigated the actions of a tricyclic antidepressant on small intestinal motor function in eight healthy volunteers and in six patients with diarrhea-predominant IBS. Fasting ambulatory motility was recorded from six small intestinal sites for 16–18 hr while on no drug (baseline) and while taking imipramine for five days. Orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, during baseline and imipramine administration. Imipramine did not alter migrating motor complex periodicity, but slowed jejunal phase III propagation velocity in controls from 7.5±1.1 to 3.6±0.5 cm/min (P<0.01) and in IBS from 7.8±0.6 to 4.4±0.5 cm/min (P<0.0001). Phase III duration at each site was increased, and total recorded phase III was greater during imipramine than baseline studies. Imipramine increased the amplitude of phase III contractions. There was no effect of imipramine on non-phase-III motility index or discrete clustered contractions. Imipramine prolonged OCTT from 73±6 min to 97±8 min in controls (P<0.05) and from 61±9 min to 89±8 min in IBS (P<0.05). Although OCTT was shorter in this IBS group, no motility differences were seen between controls and IBS. This demonstration that a tricyclic antidepressant can modify small intestinal motor function in health and in IBS supports the view that these drugs may have therapeutic actions in IBS unrelated to mood improvement.

Ambulatory small intestinal motility in 'diarrhoea' predominant irritable bowel syndrome.

Dysmotility of the duodenum and proximal jejunum has been reported in patients with irritable bowel syndrome. This study extended these findings by recording fasting ambulatory motility from electronic strain gauge sensors sited in the jejunum and ileum of eight diarrhoea predominant irritable bowel syndrome patients and 12 healthy controls. During the day, periodicity of migrating motor complexes mean (SEM) did not differ between patients (92 (10) min) and controls (85 (7) min). At night, periodicity was shorter in both patients and controls, and the daytime dominance of phase II was replaced by phase I. In both groups, aboral progression of phase III fronts was associated with a slowing of propagation velocity and maximum contractile rate, but an increase in mean amplitude of contraction. Discrete clustered contractions were seen in seven patients and 10 controls occupying 14 and 16% of daytime phase II activity, respectively. Pain episodes were not associated with any specific motility patterns. Despite the lack of motility differences between the two groups, orocaecal transit time in the irritable bowel syndrome patients was shorter at 57 (9) min than in the controls, 82 (6) min (p < 0.05). This ambulant study has failed to show any abnormalities of fasting small intestinal motility that might distinguish diarrhoea predominant irritable bowel syndrome patients from healthy controls.

Abnormal REM sleep in the irritable bowel syndrome

Motor abnormalities of the small bowel that occur only during the waking state have been reported in the irritable bowel syndrome (IBS), suggesting that central nervous system arousal is a necessary condition for expression of the disorder and that it may reflect inappropriate brain-gut interaction. This possible relationship was explored further by synchronous polysomnography and recording of upper small bowel motility in six healthy subjects and six patients with IBS. During sleep, there was no difference in the patterns of intestinal motility between the two groups. There was no difference between the rapid eye movement (REM) latency or number of REM episodes, but the proportion of REM sleep was markedly increased (36.5% +/- 5.7% vs. 18.2% +/- 5.7%; P less than 0.01) in the IBS group, although the duration of sleep was similar (468 +/- 13 minutes in IBS vs. 444 +/- 10 minutes in controls; P greater than 0.1). Sleep apnea was detected in three of six patients with IBS but was not seen in controls. The data are consistent with the model of IBS as a disorder of brain-gut interaction.

Intestinal transit in anxiety and depression.

BACKGROUND: Patients with anxiety and depression often have bowel symptoms. Until now, studies investigating a link between altered bowel habit and psychological illness have focused on patients with disturbed defecation presenting to gastroenterologists. AIMS: To determine whether patients with anxiety and depression have objective evidence of abnormal intestinal transit irrespective of any bowel symptoms. METHODS: 21 psychiatric outpatients fulfilling research criteria for generalised anxiety disorder and/or major depression, and 21 healthy volunteers were studied. Orocaecal transit time (OCTT) was measured by lactulose hydrogen breath test. Whole gut transit time (WGTT) was measured by abdominal radiography after ingestion of radio-opaque markers. RESULTS: Median (range) WGTT was shorter in patients with anxiety (14 (6-29) hours) than in patients with depression (49 (35-71) hours) (p < 0.001), and controls (42 (10-68) hours) (p < 0.001). In patients with anxiety, orocaecal transit time was shorter (60 (10-70) minutes) than in patients with depression (110 (60-180) minutes) (p < 0.01), and shorter than in controls (75 (50-140)) minutes (p < 0.05). The prolongation of transit times in depression compared with controls was not significant. However, WGTT correlated with both the Beck Depression Inventory score (r = 0.59, p < 0.01) and the depression score of the Hospital Anxiety and Depression scale (r = 0.66, p < 0.001). CONCLUSIONS: These objective measurements of intestinal transit in affective disorders are consistent with clinical impressions that anxiety is associated with increased bowel frequency, and depressed patients tend to be constipated; mood has an effect on intestinal motor function.

Abnormal illness attitudes in patients with irritable bowel syndrome

The Illness Attitudes Scales (IAS) and the Beck Depression Inventory (BDI) were administered to 40 patients with irritable bowel syndrome (IBS) and these were compared with 35 patients with organic gastrointestinal (GI) disease, 37 depressed patients, and 40 healthy volunteers. The BDI score was found to be greater in the IBS patients than in either the patients with organic disease or healthy subjects. All the patient groups had abnormal IAS scores compared with the healthy group, but these were most marked among the IBS patients with elevated scores on six out of the eight subscales. Three of these were specific to the IBS patients: bodily preoccupation, hypochondriacal beliefs and disease phobia. The results of this study indicate that clinical IBS is associated with abnormal illness attitudes which are not simply a reflection of either an associated depression or of experiencing physical symptoms.

Selective affective biasing in recognition memory in the irritable bowel syndrome.

The cognitive model of depression assigns a central role to negatively biased information processing in the pathogenesis of the emotional disorder. The relationship between depression and irritable bowel syndrome (IBS) was explored from a cognitive perspective. A word recognition memory task was constructed: subjects had to memorize and subsequently recognise a set of emotionally loaded stimulus words with either positive, neutral, or negative connotations. Four age matched groups participated--30 IBS patients, 28 depressed patients, 28 patients with organic gastrointestinal disease, and 30 healthy volunteers. The depressed patients, as would be expected, showed a significant bias in favour of emotionally negative words (p < 0.05): the IBS patients showed the same negative bias. In addition the IBS patients made significantly more false-positive type errors in recognising emotionally negative words than either the depressed patients (p < 0.05) or the healthy volunteers (p < 0.01). This suggests that the IBS patients have a peculiar confirmatory bias for negative material. This may have clinical relevance in terms of the IBS patients evaluation of their own abdominal sensory experience.

Migrating motor complex and sleep in health and irritable bowel syndrome

The human migrating motor complex (MMC) and sleep cycle have a similar periodicity, and there is some contention as to whether these biorhythms are linked. In irritable bowel syndrome (IBS), episodes of intestinal dysmotility have been described almost exclusively during wakefulness, but IBS patients often complain of poor sleep, and it has been suggested that IBS patients have increased rapid eye movement (REM) sleep. This study sought to identify any associations between sleep stage and small intestinal motility and any objective sleep abnormalities in IBS. Nocturnal motility was recorded from six small intestinal sensors mounted on a fine nasoenteric catheter in eight IBS patients and 10 healthy volunteers. Polysomnography to determine sleep stage was recorded simultaneously. The proportions of time awake, in non-REM and REM sleep were similar in controls and IBS. REM latency did not differ between the two groups despite increased depression in the IBS patients (Hamilton Depression Rating of 8.3±1.7 in IBS, 3.0±0.7 in controls,P<0.01). Nocturnal motility was similar, with phase I occupying most of the MMC cycles. There was no temporal association between MMCs and sleep stage, with no synchrony of phase III for REM episodes. The mean motility index of 4.5±0.4 during wakefulness was greater than during all sleep stages (P<0.05). During non-REM sleep stages 1 and 2, motility index of 3.2±0.3 was greater than 2.3±0.2 during stages 3 and 4 (P<0.05), but similar to motility index of 3.3±0.4 during REM sleep. Thus, sleep architecture and nocturnal small intestinal motility are normal in IBS. In health and IBS, sleep cycles and MMC cycles are independent, but motility is quantitatively influenced by sleep stage and is inversely related to the depth of sleep.

The Prevalence of Symptoms of Irritable Bowel Syndrome Among Acute Psychiatric Inpatients With an Affective Diagnosis

An interview study of 87 inpatients with affective diagnoses, according to the International Classification of Diseases (9th Edition), yielded a prevalence of irritable bowel syndrome (IBS) of 39.7%, approximately twice that found in the general population. The IBS symptoms almost invariably preceded the onset of the affective disorder, but were exacerbated by it. The consultation rate for bowel symptoms (41.9%) was greater than that in the general population. In this study, 69.2% of consulters and 55.5% of nonconsulters had experienced an exacerbation of their IBS symptoms since the onset of their emotional disorder. These findings suggest that such disorders may influence the subjective severity of IBS and also consultation behavior, but do not play a major part in the etiology of the gastrointestinal symptoms.