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SUMMARY 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. Methods: We have studied the effects of imipramine, a tricyclic antidepressant with mixed pharmacological properties, and paroxetine, a selective 5‐hydroxy‐tryptamine re‐uptake inhibitor, on intestinal transit times. Results: Median (range) whole gut transit time was lower in 10 diarrhoea‐predominant irritable bowel syndrome patients, 22.2 (3.6–51.6) h, compared to 28 control subjects 39.6 (7.2–68.4) h, (P < 0.05). Similarly, orocaecal transit time was shorter at 55 (30–90) min in diarrhoea‐predominant irritable bowel syndrome patients compared to 75 (40–150) min in controls, (P < 0.05). Four days’administration of imipramine increasing to a daily dose of 100 mg prolonged both orocaecal and whole gut transit times in 12 control subjects and six diarrhoea‐predominant irritable bowel syndrome patients. In contrast, 30 mg paroxetine daily for 4 days reduced orocaecal transit time in ten controls and eight irritable bowel syndrome patients, but had no effect on whole gut transit time. Conclusion: Short‐term administration of antidepressants alters intestinal transit, but the selective 5‐hydroxytryptamine re‐uptake inhibitor, paroxetine, has different effects to the tricyclic drug, imipramine. These effects on transit precede any effects on mood. Although there is a high prevalence of affective disorder in irritable bowel syndrome clinic patients, these drugs may have additional therapeutic actions on the gut. These actions might be taken into account when prescribing antidepressants in 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 ofmotility 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 predomiiant irritable bowel syndrome patients from healthy controls. (Gut 1994; 35: 203-210) complex (MMC Abdominal symptoms in IBS may originate from organs other than the colon.34 The small intestine has been studied as a site of possible dysmotility. In contrast with the colon, normal patterns of motility are more clearly defined in the small intestine,5" although there is considerable variability in health.'"0' During fasting the small intestine exhibits a distally migrating cycle of motility, the interdigestive migrating motor SUBJECTS Eight patients (four men, four women, mean age 36 years, range 24-53) attending the gastroenterology clinic with a diagnosis of IBS22 23 were studied. All complained of 'diarrhoea' as their predominant bowel habit and were selected because of the severity of their symptoms. These

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<005), 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<005). 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. (Gut 1994; 35: 496-500) nature is poorly understood.'0 In animals, migrating motor complex cycling can be modified by administration of 5-HT, its precursor 5-hydroxytryptophan, and its antagonists." '4 The effect of 5-HT on the migrating motor complex in humans has not been studied. Tachyphylaxis to 5-HT given intravenously,45 and associated cardiovascular and pulmonary responses limit prolonged infusion of 5-HT in humans. The effect, however, of 5-HT agonism on human small intestinal motor function might be alternatively investigated using a selective 5-HT reuptake inhibitor. Paroxetine selectively inhibits the neuronal reuptake of 5-HT, increasing the availability of synaptic 5-HT. Its ability to inhibit 5-HT reuptake exceeds its ability to inhibit noradrenaline reuptake by a factor of 320," making it four to five hundred times as selective as the standard tricycic antidepressants imipramine and amitriptyline. Unlike traditional tricyclic drugs, paroxetine has negligible affinity for muscarinic cholinergic receptors and does not bind at other neurotransmitter receptor sites. Although paroxetine is used for its action in the central nervous system, enteric 5-HT neurones resemble central 5-HT neurones in their response to 5-HT reuptake inhibitors.'6 The aim of this study was to use the 5-HT reuptake inhibitor paroxetine as an indirect 5-HT agonist, to examine the longer term effects of 5-HT on human small intestinal motility and transit. The gastrointestinal tract is the main source of 5-hydroxytryptamine (5-HT) in humans. In the small intestine, 5-HT is found predominantly within the enterochromaffin cells of the mucosa, but significant amounts of 5-HT are also found within the myenteric plexus. In addition to its role in the intestinal secreti...

(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 oftransit 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.