'Idiopathic' intestinal failure--the importance of identifying and treating primary psychopathology.

BACKGROUND: Gastrointestinal neuromuscular disorders (GINMD) are an important cause of intestinal failure (IF). We present six cases of IF in whom a diagnosis of GINMD was initially suspected, but in whom psychopathology was discovered to be the primary etiology. METHODS: (i) Six consecutive cases referred to our unit with IF, initially presumed to be due to GINMD, were selected. Informed consent was obtained from all patients. Case notes were reviewed for salient clinical information. (ii) A literature search was performed to ascertain the epidemiology of psychopathology in IF and the current evidence for the management of severe functional GI disorders with a multidisciplinary psychiatric approach. KEY RESULTS: (i)All six cases required multidisciplinary psychiatric management in a specialized psychiatric unit that included the use of antidepressants, antipsychotics, mood stabilizers, and Electroconvulsive therapy in addition to nutritional support via enteral or parenteral routes. (ii) The evidence base for the treatment of severe FGIDs is sparse. CONCLUSIONS & INFERENCES: There is a need for additional reporting of such cases and further research. Our experience would suggest that a delay in the involvement of a specialist liaison psychiatrist has the potential to be life threatening in such cases. This may be more likely with greater severity, where the apparent predominance of 'physical' symptoms generates reluctance in both patient and physician to consider a psychiatric etiology and also appears to occur due to a lengthier investigative process than existed previously. We therefore propose that the provision of a specialist psychiatric assessment for all patients presenting with IF is indicated at the point of initial clinical contact, based upon the substantial clinical benefit it has the potential to confer upon a significant minority. This process need not delay investigation, which can continue as indicated in parallel, but can be life-saving.

Review article: The rationale for antidepressant therapy in functional gastrointestinal disorders.

The rationale for antidepressants in the treatment of functional gastrointestinal disorders (FGDs) has been the subject of much interest. However, because of our incomplete understanding of FGDs, this rationale remains unclear. A key point is whether the high degree of psychiatric co-morbidity associated with FGDs (40-90%) represents a shared pathophysiology or the ascertainment bias of tertiary referral patients. Our aims were four-fold: (i) to review the current rationale for antidepressant therapy in FGDs; (ii) to review the studies comparing the characteristics of FGDs with both organic gastrointestinal disease and psychiatric disorders; (iii) to propose a model of FGDs which explains the high psychiatric co-morbidity; (iv) to compare the treatment regimes and effectiveness of antidepressants in FGDs and psychiatric illnesses. The review highlights two important observations. Firstly, the characteristics of FGDs are similar to those of affective disorders and dissimilar to those of organic disease. Secondly, although antidepressants benefit FGD sufferers, their benefits in psychiatric illnesses are greater. We conclude that, in view of the degree of similarity between FGDs and affective disorders, FGDs could be considered as affective disorders in their own right and, if the prescription of antidepressants conformed to their use in affective disorders, FGD morbidity would be reduced.

Prevalence of irritable bowel syndrome in chronic fatigue.

The aetiologies of irritable bowel syndrome and chronic fatigue are unknown. Psychological as well as physical factors have been implicated in both. Fatigue is common in irritable bowel syndrome patients. The purpose of the study was to determine the prevalence of irritable bowel syndrome in chronic fatigue sufferers. A bowel symptom questionnaire was sent to all 4,000 members of a self-help group for fatigue sufferers. Of the 1,797 who responded, 1,129 (63%) fulfilled a diagnosis of irritable bowel syndrome (recurrent abdominal pain and at least three Manning criteria). This greatly exceeds estimates of irritable bowel syndrome prevalence of up to 22% in the general population. Furthermore, irritable bowel syndrome sufferers within this chronic fatigue population reported more Manning criteria (14% had all six Manning criteria) than irritable bowel syndrome sufferers in the general population. This study demonstrates an overlap of symptoms in chronic fatigue and irritable bowel syndrome. In chronic fatigue, irritable bowel symptoms may be one aspect of a more generalised disorder.

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.

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 IRS 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 was 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. This sleep architecture and nocturnal small intestinal motility are normal in IBS.(ABSTRACT TRUNCATED AT 250 WORDS)

Central 5-hydroxytryptaminergic function in irritable bowel syndrome.

BACKGROUND: Psychological factors may contribute to the aetiology and exacerbation of symptoms in irritable bowel syndrome (IBS), suggesting that the central nervous system may be an important site of dysfunction in IBS. Hormonal responses after a serotonergic challenge assess the functional integrity of central 5-hydroxytryptaminergic pathways and are diminished in depression. The aim of this study was to determine whether hormonal responses in IBS after a serotonergic challenge would be decreased, as in depression, or exaggerated, as have been reported in another functional gastrointestinal disorder, nonulcer dyspepsia. METHODS: Fourteen IBS patients, 16 healthy volunteers, and 9 patients with inflammatory bowel disease were given 30 mg d-fenfluramine, a selective stimulus to central 5-hydroxytryptaminergic pathways. RESULTS: Plasma prolactin and cortisol concentrations during the following 5 h increased to a similar extent in all three subject groups, despite increased levels of anxiety and depression (as scored on the Hospital Anxiety and Depression Scale and Beck Depression Inventory) in the IBS and inflammatory bowel disease patients compared with the healthy controls. Base-line cortisol concentration correlated with the magnitude of affective disorder. CONCLUSION: In contrast to the alterations of central 5-hydroxytryptamine receptor sensitivity seen in depression and non-ulcer dyspepsia, central 5-hydroxytryptaminergic pathways function normally in IBS.

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 the IBS group, no motility differences were seen between controls and IBS. This demonstration that a tricylic 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.

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. METHODS: We have studied the effects of imipramine, a tricyclic antidepressant with mixed pharmacological properties, and paroxetine, a selective 5-hydroxytryptamine 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.

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.

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.

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.

Plasma prolactin, adrenocorticotrophic hormone and cortisol after administration of d-fenfluramine or placebo to healthy subjects.

Hormonal responses following single doses of the racemic drug d,l-fenfluramine have been used as an index of central 5-hydroxytryptamine (5-HT) function. We wished to evaluate normal responses to d-fenfluramine, which is more specific at stimulating 5-HT pathways. Twelve healthy volunteers were given 30 mg oral d-fenfluramine and placebo in a randomized single-blind crossover design. Following d-fenfluramine there was a rise in plasma prolactin, but no ACTH response. Cortisol levels did not rise above baseline values, but d-fenfluramine diminished the circadian fall in cortisol output, and cortisol levels were slightly higher after d-fenfluramine than after placebo. Unlike d,l-fenfluramine, d-fenfluramine is not a potent stimulus for ACTH and cortisol release. Hormonal responses following d-fenfluramine provide a more accurate assessment of the functional integrity of central 5-HT activity.

The social toll of Crohn's disease.

Eighty-five outpatients with Crohn's disease who knew their diagnosis and that the disease was subject to relapse were interviewed. The personalities of the women as measured by the Eysenck personality questionnaire were similar to those of a control group, but the men were more neurotic and introverted. Most patients continued to live optimistic, useful lives; they felt well, continued to work, hoped that their disease would not deteriorate in the future, and often had an improved relationship with their spouse despite less frequent sexual intercourse. We found that the successful adaptation of patients to this chronic disease was more closely related to their personality than to the activity or extent of the disease.