Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. METHODS: This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. FINDINGS: Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. INTERPRETATION: To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).

Factors associated with lower disease-specific and generic health-related quality of life in Rome IV irritable bowel syndrome.

BACKGROUND: Little is known about associations with reduced quality of life in irritable bowel syndrome (IBS) or impact of IBS on quality of life compared with other chronic conditions. METHODS: We collected demographic, gastrointestinal and psychological symptoms, healthcare usage, direct healthcare costs, impact on work and activities of daily living data from 752 individuals with Rome IV-defined IBS. We used the irritable bowel syndrome quality of life (IBS-QOL) and the EQ-5D-5L questionnaires to examine characteristics associated with lower quality of life. RESULTS: The mean IBS-QOL among all 752 individuals with Rome IV IBS was 48.4 (SD 22.3) and the mean EQ-5D score was 0.570 (SD 0.283), the latter being comparable to people with stroke, leg ulcers or chronic obstructive pulmonary disease. Lower levels of both disease-specific and generic quality of life were associated with severe IBS symptom scores, abnormal anxiety or depression scores, and higher somatoform symptom-reporting and gastrointestinal symptom-specific anxiety scores (p < 0.001 for all analyses). Those with lower quality of life had significantly higher healthcare usage and direct healthcare costs and more impairment in work and activities of daily living (p < 0.01 for all analyses). Avoidance of alcohol, lower educational level, abnormal anxiety, depression or somatoform symptom-reporting scores, and impairment in social leisure activities, home management or maintaining close relationships were all independently associated with lower quality of life. CONCLUSION: IBS has a substantial impact on the quality of life of those affected, and worse than observed in some severe chronic organic conditions.

Characteristics and Effect of Anxiety and Depression Trajectories in Inflammatory Bowel Disease.

INTRODUCTION: Symptoms of common mental disorders, such as anxiety or depression, are associated with adverse clinical outcomes in inflammatory bowel disease (IBD). We report trajectories of these symptoms in IBD, patient characteristics associated with different trajectories, and effects on healthcare utilization and prognosis. METHODS: We collected demographic, symptom, psychological, and quality-of-life data, with questionnaires at 3-month intervals, over 12 months of follow-up. We collected healthcare utilization and IBD outcomes through notes review. We compared characteristics of those with persistently normal or improving anxiety or depression scores with those with persistently abnormal or worsening scores and the number of flares, glucocorticosteroid prescriptions, escalations of therapy, hospitalizations, or intestinal resections due to IBD activity. RESULTS: Among 771 and 777 patients, respectively, worsening or persistently abnormal anxiety or depression scores were associated with increased antidepressant (28.6% vs 12.3% anxiety, 35.8% vs 10.1% depression, P < 0.001) and opiate use (19.0% vs 7.8% anxiety, P = 0.001 and 34.0% vs 7.4% depression, P < 0.001), compared with those with persistently normal or improving scores. These individuals were also more likely to have been diagnosed with IBD in the last 12 months (16.3% vs 5.0% anxiety, P = 0.001, and 15.1% vs 5.5% depression, P = 0.006), to have clinically active disease at baseline (57.1% vs 26.6% anxiety and 71.7% vs 29.1% depression, P < 0.001) and lower quality-of-life scores ( P < 0.001). Individuals with worsening or persistently abnormal trajectories of anxiety or depression required significantly more outpatient appointments, radiological investigations, and endoscopic procedures for IBD-related symptoms. DISCUSSION: In this 12-month follow-up study, patients with IBD with worsening or persistently high anxiety or depression scores were higher utilizers of health care but were not at an increased risk of future adverse disease outcomes.

A Novel Method to Classify and Subgroup Patients With IBS Based on Gastrointestinal Symptoms and Psychological Profiles.

INTRODUCTION: Conventionally, patients with irritable bowel syndrome (IBS) are subgrouped based on their predominant bowel habit. Given the relevance of psychological comorbidity to IBS symptoms, our aim was to explore an alternative approach to subgrouping by incorporating factors beyond stool form and frequency. METHODS: We collected demographic, symptom, and psychological health data from 1,375 adult subjects in the community who self-identified as having IBS, identifying 2 cohorts meeting either Rome III or Rome IV criteria. In each cohort, we performed latent class analysis, a method of model-based clustering, to identify specific subgroups (clusters). For each cluster, we drew a radar plot and compared these by visual inspection, describing cluster characteristics. RESULTS: In total, 1,080 individuals met the Rome III criteria for IBS, and 811 met the Rome IV criteria. In both cohorts, a 7-cluster model was the optimum solution, and the characteristics of the clusters were almost identical between Rome III and IV. Four clusters were defined by the pattern of gastrointestinal symptoms (loose stools and urgency or hard stools and bloating), further differentiated by the presence of abdominal pain not relieved by defecation, and by the extent of psychological comorbidity. Two clusters had below-average gastrointestinal symptoms, differentiated by the extent of psychological comorbidity. The final cluster had well-above-average gastrointestinal symptoms and high levels of psychological comorbidity. The proportion of subjects with severe IBS symptom scores, high levels of perceived stress, and high levels of gastrointestinal symptom-specific anxiety was significantly higher in clusters with high psychological comorbidity (P < 0.001). DISCUSSION: Latent class analysis identified 7 distinct IBS subgroups characterized by varying degrees of gastrointestinal symptoms, extraintestinal symptoms, and psychological comorbidity. Further research is needed to assess whether they might be used to direct treatment.

Bi-directionality of Brain-Gut Interactions in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are associated with mood disorders, such as anxiety or depression, but it is not clear whether one contributes to development of the other, or if the interaction is bi-directional (anxiety or depression contributes to the progression of IBD, and IBD affects psychological health). We performed a 2-year longitudinal prospective study of patients in secondary to care investigate the bi-directionality of IBD and mood disorders. METHODS: We collected data from 405 adult patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) from November 2012 through June 2017. Demographic features, subtypes of IBD, treatments, symptoms, somatization, and fecal level of calprotectin were recorded at baseline. IBD activity was determined at baseline and after the follow-up period (2 years or more) using the Harvey-Bradshaw Index for CD and the Simple Clinical Colitis Activity Index for UC (scores ≥5 used to define disease activity). Anxiety and depression data were collected using the Hospital Anxiety and Depression Scale (HADS), at baseline and after the follow-up period. Objective markers of disease activity, including glucocorticosteroid prescription or flare of disease activity, escalation of therapy, hospitalization secondary to IBD activity, and intestinal resection during follow-up were assessed via case note review. A brain-gut direction of disease activity was defined as development of new IBD activity in patients with quiescent IBD and abnormal HADS scores at baseline. A gut-brain direction of disease activity was defined by subsequent development of abnormal HADS scores in patients with active IBD and normal HADS scores at baseline. We performed multivariate Cox regression controlling for patient characteristics and follow-up duration. RESULTS: Baseline CD or UC disease activity were associated with an almost 6-fold increase in risk for a later abnormal anxiety score (hazard ratio [HR], 5.77; 95% CI, 1.89-17.7). In patients with quiescent IBD at baseline, baseline abnormal anxiety scores were associated with later need for glucocorticosteroid prescription or flare of IBD activity (HR, 2.08; 95% CI, 1.31-3.30) and escalation of therapy (HR, 1.82; 95% CI, 1.19-2.80). These associations persisted when normal IBD activity index scores and fecal level of calprotectin <250 µg/g were used to define quiescent disease at baseline. CONCLUSIONS: In a 2-year study of patients with CD or UC, we found evidence for bi-directional effects of IBD activity and psychological disorders. Patients with IBD should be monitored for psychological well-being.

An analysis of whether a working-age ward-based liaison psychiatry service requires the input of a liaison psychiatrist.

Aims and method This article presents a 12-month case series to determine the fraction of ward referrals of adults of working age who needed a liaison psychiatrist in a busy tertiary referral teaching hospital. Results The service received 344 referrals resulting in 1259 face-to-face contacts. Depression accounted for the most face-to-face contacts. We deemed the involvement of a liaison psychiatrist necessary in 241 (70.1%) referrals, with medication management as the most common reason. Clinical implications A substantial amount of liaison ward work involves the treatment and management of severe and complex mental health problems. Our analysis suggests that in the majority of cases the input of a liaison psychiatrist is required.

Depression predicts future emergency hospital admissions in primary care patients with chronic physical illness.

OBJECTIVE: More than 15 million people currently suffer from a chronic physical illness in England. The objective of this study was to determine whether depression is independently associated with prospective emergency hospital admission in patients with chronic physical illness. METHOD: 1860 primary care patients in socially deprived areas of Manchester with at least one of four exemplar chronic physical conditions completed a questionnaire about physical and mental health, including a measure of depression. Emergency hospital admissions were recorded using GP records for the year before and the year following completion of the questionnaire. RESULTS: The numbers of patients who had at least one emergency admission in the year before and the year after completion of the questionnaire were 221/1411 (15.7%) and 234/1398 (16.7%) respectively. The following factors were independently associated with an increased risk of prospective emergency admission to hospital: having no partner (OR 1.49, 95% CI 1.04 to 2.15); having ischaemic heart disease (OR 1.60, 95% CI 1.04 to 2.46); having a threatening experience (OR 1.16, 95% CI 1.04 to 1.29); depression (OR 1.58, 95% CI 1.04 to 2.40); and emergency hospital admission in the year prior to questionnaire completion (OR 3.41, 95% CI 1.98 to 5.86). CONCLUSION: To prevent potentially avoidable emergency hospital admissions, greater efforts should be made to detect and treat co-morbid depression in people with chronic physical illness in primary care, with a particular focus on patients who have no partner, have experienced threatening life events, and have had a recent emergency hospital admission.

'I wouldn't push that further because I don't want to lose her': a multiperspective qualitative study of behaviour change for long-term conditions in primary care.

BACKGROUND: Health outcomes for long-term conditions (LTCs) can be improved by lifestyle, dietary and condition management-related behaviour change. Primary care is an important setting for behaviour change work. Practitioners have identified barriers to this work, but there is little evidence examining practices of behaviour change in primary care consultations and how patients and practitioners perceive these practices. OBJECTIVE: To examine how behaviour change is engaged with in primary care consultations for LTCs and investigate how behaviour change is perceived by patients and practitioners. DESIGN: Multiperspective, longitudinal qualitative research involving six primary health-care practices in England. Consultations between patients with LTCs and health-care practitioners were audio-recorded. Semi-structured interviews were completed with patients and practitioners, using stimulated recall. Patients were re-interviewed 3 months later. Framework analysis was applied to all data. PARTICIPANTS: Thirty-two people with at least one LTC (chronic obstructive pulmonary disease, diabetes, asthma and coronary heart disease) and 10 practitioners. RESULTS: Behaviour change talk in consultations was rare and, when it occurred, was characterized by deflection and diffidence on the part of practitioners. Patient motivation tended to be unaddressed. While practitioners positioned behaviour change work as outside their remit, patients felt uncertain about, yet responsible for, this work. Practitioners raised concerns that this work could damage other aspects of care, particularly the patient-practitioner relationship. CONCLUSION: Behaviour change work is often deflected or deferred by practitioners in consultations, who nevertheless vocalize support for its importance in interviews. This discrepancy between practitioners' accounts and behaviours needs to be addressed within primary health-care organizations.

How QOF is shaping primary care review consultations: a longitudinal qualitative study.

BACKGROUND: Long-term conditions (LTCs) are increasingly important determinants of quality of life and healthcare costs in populations worldwide. The Chronic Care Model and the NHS and Social Care Long Term Conditions Model highlight the use of consultations where patients are invited to attend a consultation with a primary care clinician (practice nurse or GP) to complete a review of the management of the LTC. We report a qualitative study in which we focus on the ways in which QOF (Quality and Outcomes Framework) shapes routine review consultations, and highlight the tensions exposed between patient-centred consulting and QOF-informed LTC management. METHODS: A longitudinal qualitative study. We audio-recorded consultations of primary care practitioners with patients with LTCs. We then interviewed both patients and practitioners using tape-assisted recall. Patient participants were followed for three months during which the research team made weekly contact and invited them to complete weekly logs about their health service use. A second interview at three months was conducted with patients. Analysis of the data sets used an integrative framework approach. RESULTS: Practitioners view consultations as a means of 'surveillance' of patients. Patients present themselves, often passively, to the practitioner for scrutiny, but leave the consultation with unmet biomedical, informational and emotional needs. Patients perceived review consultations as insignificant and irrelevant to the daily management of their LTC and future healthcare needs. Two deviant cases, where the requirements of the 'review' were subsumed to meet the patient's needs, focused on cancer and bereavement. CONCLUSIONS: Routine review consultations in primary care focus on the biomedical agenda set by QOF where the practitioner is the expert, and the patient agenda unheard. Review consultations shape patients' expectations of future care and socialize patients into becoming passive subjects of 'surveillance'. Patient needs outside the narrow protocol of the review are made invisible by the process of review except in extreme cases such as anticipating death and bereavement. We suggest how these constraints might be overcome.

Why do patients with long-term conditions use unscheduled care? A qualitative literature review.

Unscheduled care (UC) refers to non-routine face-to-face care, such as accident and emergency care, out-of-hours care, or walk-in centres. Current health service policy aims to reduce its use. Unscheduled care is common in people with long-term conditions such as diabetes, asthma, chronic obstructive pulmonary disease and coronary heart disease. By reviewing qualitative research literature, we aimed to understand the breadth of psychosocial and other influences on UC use in people with long-term conditions. Few qualitative papers specifically address UC in patients in these disease groups. Therefore, our literature search also included qualitative research that explored factors potentially relevant to UC use, including attitudes to healthcare use in general. By searching Medline, Embase, Psycinfo and Cinahl from inception to 2011, we identified 42 papers, published since 1984, describing relevant original research and took a meta-ethnographic approach in reviewing them. The review was conducted between Spring 2009 and April 2011, with a further search in December 2011. Most papers reported on asthma (n = 13) or on multiple or unspecified conditions (n = 12). The most common methods reported were interviews (n = 33) and focus groups (n = 13), and analyses were generally descriptive. Theoretical and ethical background was rarely explicit, but the implicit starting point was generally the 'problem' of UC, and health-care, use in general, decontextualised from the lives of the patients using it. Patients' use of UC emerged as understandable, rational responses to pressing clinical need in situations in which patients thought it the only option. This belief reflected the value that they had learned to attach to UC versus routine care through previous experiences. For socially or economically marginalised patients, UC offered access to clinical or social care that was otherwise unavailable to them.