Lesley A. Graff

Depression and anxiety in inflammatory bowel disease: A review of comorbidity and management

Abstract While there has been a great deal of speculation over the years on the importance of emotional factors in inflammatory bowel disease (IBD), it is only in the last decade or so that studies with stronger designs have been available to clarify the nature of this relationship. This review considers recent evidence on the prevalence of anxiety and depressive disorders in IBD, the role of these disorders as a risk factor for IBD onset, the degree to which they affect the course of the IBD, and the contribution of corticosteroid treatment to psychiatric symptom onset. There is evidence that anxiety and depression are more common in patients with IBD and that the symptoms of these conditions are more severe during periods of active disease. The few studies that address the issue of anxiety and depression as risk factors for IBD do not yet provide enough information to support definite conclusions. There is evidence, however, that the course of the disease is worse in depressed patients. Treatment with corticosteroids can induce mood disorders or other psychiatric symptoms. The second part of the review focuses on patient management issues for those with comorbid anxiety or depression. Practical approaches to screening are discussed, and are recommended for routine use in the IBD clinic, especially during periods of active disease. We review evidence‐based pharmacological and psychological treatments for anxiety and depression and discuss practical considerations in treating these conditions in the context of IBD to facilitate overall management of the IBD patient.

A prospective population-based study of triggers of symptomatic flares in IBD.

OBJECTIVES:We aimed to determine whether any of the nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, infections, and stress trigger symptomatic flares of inflammatory bowel diseases (IBDs).METHODS:Participants drawn from a population-based IBD research registry were surveyed every 3 months for 1 year. They simultaneously tracked the use of NSAIDs, antibiotics, infections, major life events, mood, and perceived stress. Social networks, childhood socioeconomic status, and smoking were assessed at baseline. Disease flare was identified using the Manitoba Inflammatory Bowel Disease Index, a validated disease activity index. Across any two consecutive survey periods, participants were categorized as having a flare (inactive/active), having no flare (inactive/inactive), or remaining active (active/active). Potential triggers were evaluated for the first 3-month period to determine predictive rather than concurrent relationships. Data from only one pair of 3-month periods from an individual were analyzed.RESULTS:A total of 704 participants completed the baseline survey; 552 (78.3%) returned all 5 surveys. In all, 174 participants who had a flare were compared with 209 who had no flare. Perceived stress, negative affect (mood), and major life events were the only trigger variables significantly associated with flares. There were no differences between those who flared and those who did not, in the use of NSAIDs, antibiotics, or in the presence of infections. Multivariate logistic regression analyses indicated that only high-perceived stress (adjusted odds ratio=2.40 (1.35, 4.26)) was associated with an increased risk of flare.CONCLUSIONS:This study adds to the growing evidence that psychological factors contribute to IBD symptom flares. There was no support for differential rates of use of NSAIDS, antibiotics, or for the occurrence of (non-enteric) infections related to IBD flares.

The Manitoba IBD Cohort Study: A Population-Based Study of the Prevalence of Lifetime and 12-Month Anxiety and Mood Disorders

BACKGROUNDG AND AIMS: ven the impact of anxiety and mood disorders on health, it is important to consider these disorders in persons with inflammatory bowel disease (IBD). We assessed the prevalence of anxiety and mood disorders in a population-based IBD cohort.METHODS:A structured diagnostic interview was administered to participants in the cohort (N = 351), and rates were compared to age-, gender-, and region-matched controls drawn from a national survey (N = 779).RESULTS: A comparison of lifetime prevalence suggests higher rates of panic, generalized anxiety, and obsessive-compulsive disorders and major depression and lower rates of social anxiety and bipolar disorders in the IBD sample than in national samples in the United States and New Zealand. Direct comparisons with matched controls (with data available for three anxiety disorders) found lifetime prevalence (IBD vs controls) as follows: social anxiety disorder lower in IBD (6% vs 11%, OR 0.52, 95% CI 0.32–0.85), panic disorder not significantly different (8.0% vs 4.7%, OR 1.59, 95% CI 0.96–2.63), agoraphobia without panic not significantly different (1.1% vs 0.6%, OR 1.44, 95% CI 0.37–5.55), and major depression higher (27.2% vs 12.3%, OR 2.20, 95% CI 1.64–2.95). Comparing IBD respondents with and without lifetime anxiety or mood disorder, those with a disorder reported lower quality of life and earlier onset of IBD symptoms and there was a trend toward earlier IBD diagnosis.CONCLUSIONS:Clinicians should be aware of the increased prevalence of depression and possibly other anxiety disorders in persons with IBD as these disorders may influence response to treatment and quality of life.

Predictors of medication adherence in inflammatory bowel disease.

BACKGROUND AND AIMS:This study reports cross-sectional medication adherence data from year 1 of the Manitoba Inflammatory Bowel Disease (IBD) Cohort Study, a longitudinal, population-based study of multiple determinants of health outcomes in IBD in those diagnosed within 7 yr.METHODS:A total of 326 participants completed a validated multi-item self-report measure of adherence, which assesses a range of adherence behaviors. Demographic, clinical, and psycho-social characteristics were also assessed by survey. Adherence was initially considered as a continuous variable and then categorized as high or low adherence for logistic regression analysis to determine predictors of adherence behavior.RESULTS:Using the cutoff score of 20/25 on the Medication Adherence Report Scale, high adherence was reported by 73% of men and 63% of women. For men, predictors of low adherence included diagnosis (UC: OR 4.42, 95% CI 1.66–11.75) and employment status (employed: OR 11.27, 95% CI 2.05–62.08). For women, predictors of low adherence included younger age (under 30 versus over 50 OR 3.64, 95% CI 1.41–9.43; under 30 vs. 40–49 yr: OR 2.62, 95% CI 1.07–6.42). High scores on the Obstacles to Medication Use Scale strongly related to low adherence for both men (OR 4.05, 95% CI 1.40–11.70) and women (OR 3.89, 95% CI 1.90–7.99). 5-ASA use (oral or rectal) was not related to adherence. For women, immunosuppressant use versus no use was associated with high adherence (OR 4.49, 95% CI 1.58–12.76). Low trait agreeableness was associated with low adherence (OR 2.03, 95% CI 1.12–3.66).CONCLUSIONS:Approximately one-third of IBD patients were low adherers. Predictors of adherence differed markedly between genders, although obstacles such as medication cost were relevant for both men and women.

Longitudinal study of quality of life and psychological functioning for active, fluctuating, and inactive disease patterns in inflammatory bowel disease.

Background: The aim was to assess quality of life (QOL) and psychological functioning in inflammatory bowel disease (IBD) as related to patterns of disease activity over time. Methods: Study participants were 388 recently diagnosed individuals from the population‐based Manitoba IBD Cohort Study. They completed mail‐out surveys at 6‐month intervals and clinical interviews annually. Based on their 2‐year pattern of self‐reported disease activity, participants were assigned to 1 of 3 groups: consistently active, fluctuating, or consistently inactive disease. Disease type (Crohns disease [CD] or ulcerative colitis [UC]) was confirmed through chart review. Change over time was modeled for measures of QOL and positive and negative psychological functioning using mixed‐effects regression analyses. Results: Half of the participants had fluctuating disease activity, while almost one‐third of participants reported consistent active disease. Participants with the fluctuating activity pattern showed significant improvement in disease‐specific QOL compared to participants with consistent activity. Perceived stress, health anxiety, and pain anxiety decreased while pain catastrophizing and mastery increased over time, although the amount of change was not significantly different among disease activity patterns. However, when the data were averaged over time there were significant differences among disease activity patterns on most outcomes. Significant effects of CD versus UC were observed only for the pain measures. Conclusions: Change in IBD QOL is influenced by ones longitudinal profile of disease activity, but change in psychological functioning is not. Effects of disease activity on psychological functioning were modest, suggesting that disease has an impact even when patients are not experiencing active symptoms.

A population-based study of fatigue and sleep difficulties in inflammatory bowel disease

Background: There has been little investigation of fatigue, a common symptom in inflammatory bowel disease (IBD). The aim of this study was to evaluate fatigue more comprehensively, considering relationships with psychological and biological factors simultaneously in a population‐based IBD community sample. Methods: Manitoba IBD Cohort Study participants (n = 318; 51% Crohns disease [CD]) were assessed by survey, interview, and blood sample. Fatigue, sleep quality, daytime drowsiness, stress, psychological distress, and quality of life were measured with validated scales. Hemoglobin (Hg) and C‐reactive protein (CRP) levels were also obtained. Differences were tested across disease activity and disease subtype. Results: Elevated CRP was found for 23% of the sample and 12% were anemic; 46% had active disease. Overall, 72% of those with active and 30% with inactive disease reached clinical thresholds for fatigue (Multidimensional Fatigue Inventory; P < 0.001); 77% and 49% of those with active or inactive disease, respectively, experienced poor sleep (P < 0.001). There were few differences between those with CD and ulcerative colitis (UC) on the factors assessed, except for higher CRP levels in CD (mean 8.8 versus 5.3, P < 0.02). Multiple logistic regression analyses found that elevated fatigue was associated with active disease (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.2–7.8), poor sleep quality (OR 4.0, 95% CI 1.9–8.6), and perceived stress (OR 4.2, 95% CI 2.2–8.1), but not with hours of sleep, Hg, or CRP. Conclusions: Fatigue and poor sleep are not only highly prevalent in active disease, but both are still significant concerns for many with inactive disease. Psychological factors are associated with fatigue in IBD in addition to disease and sleep considerations. (Inflamm Bowel Dis 2011;)

Do NSAIDs, antibiotics, infections, or stress trigger flares in IBD?

Non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, enteric or other systemic infections, and stress have all been reported to be potential triggers of inflammatory bowel disease (IBD). Although a mechanism of triggering a flare of IBD can be hypothesized for each factor, the associations of these factors with flares of IBD remains confusing. In this review, we analyze the literature that explores these associations. There is some evidence to support an association between NSAID use and flares but little data to associate antibiotic use directly with flares. An important connection between antibiotic use and an exacerbation of symptoms is through the development of Clostridium difficile infections. However, for all enteric infections, including C. difficile, it is unclear whether these infections simply trigger symptoms in patients with IBD that resolve on resolution of the infection, or whether they truly trigger a flare of intestinal inflammation that outlasts the infection. There is a paucity of evidence that other systemic infections trigger flares of IBD. Although there is strong evidence for an association between perceived stress levels and flares, there is a weaker association between a simple accounting of stressful life events and flares. Much of the literature is limited by a lack of adequate control groups and failure to report on base rates in the population under study (i.e., NSAIDs and antibiotic use, occurrence of infections, and stress levels). More large population-based matched cohort or case crossover studies and a continued emphasis on prospective designs are needed to better explore these potential associations. Clinical implications given the current state of knowledge are discussed.

Stress Coping, Distress, and Health Perceptions in Inflammatory Bowel Disease and Community Controls

OBJECTIVES:This study compares a community inflammatory bowel disease (IBD) sample of individuals with a matched non-IBD community sample of individuals on psychological functioning and health perceptions.METHODS:Participants in the population-based Manitoba IBD Cohort Study (n=388) were directly compared with sex-, age-, and region-matched controls from a national random-sample health survey on the aspects of psychological health, coping, and perceived general health.RESULTS:Overall, the IBD sample had lower psychological well-being and mastery, as well as higher distress than did the non-IBD controls (P≤0.02). Those with IBD used avoidant coping significantly more often, and active coping modestly more often than did the non-IBD sample; both had similar levels of “self-soothing” behaviors. Patients with Crohns disease and ulcerative colitis had similarly poor levels of functioning along these dimensions compared with the non-IBD sample, as did those with active disease (P<0.01). However, those with inactive disease were similar to the non-IBD sample, and had modestly higher mastery levels. Whereas nearly half of the non-IBD group reported chronic health conditions, those with IBD were threefold more likely to report poorer health (odds ratio 3.07, 95% confidence interval: 2.10–4.47). Psychological factors explained a greater amount of variance in perceived health for the IBD than for the non-IBD sample.CONCLUSIONS:Those with IBD have significantly poorer psychological health than do those without IBD and view their general health status more negatively, although adaptive stress-coping strategies were similar. However, when disease is quiescent there is little detriment to functioning. Active disease should be a flag to consider psychological needs in the care of an IBD patient.

Controversies Revisited: A Systematic Review of the Comorbidity of Depression and Anxiety with Inflammatory Bowel Diseases.

Background:Although mental health concerns are known to occur commonly for those with inflammatory bowel diseases (IBD), the nature of this comorbid relationship has not been systematically reviewed to date. A review in 2007 identified 5 controversies regarding anxiety/depression rates and various comparators between and within IBD. We aimed to systematically analyze and critique the current evidence regarding this comorbidity, providing an update to the 5 controversies. Methods:Ebscohost Medline, CINAHL, Embase, and PsychINFO were searched between 2005 and 2014 using systematic review methodology. Controlled quantitative studies examining either symptoms or diagnoses of anxiety and depression in IBD were included in the review, with study quality assessed using a scale developed a priori to evaluate observational research. Results:(1) IBD versus healthy controls (pooled mean proportions) (n = 13 studies): anxiety 19.1% versus 9.6%, depression 21.2% versus 13.4%; (2) IBD inactive versus IBD active disease (n = 26): anxiety 28.2% versus 66.4%, depression 19.9% versus 34.7%; (3) ulcerative colitis versus Crohns disease (n = 28): anxiety 31% versus 37%, depression 22% versus 24.4%; (4) IBD versus other chronic medical conditions (n = 17): anxiety 41.9% versus 48.2%, depression 14.5% versus 28.4%; (5) onset of anxiety/depression before or after IBD onset (n = 2): adults more likely to develop anxiety/depression before IBD onset, but a substantial proportion develops depression after onset; an increased risk for children of developing anxiety/depression after IBD onset. Conclusions:The high rates of anxiety and depression for those with IBD, particularly when disease is active, warrant a systemic approach to screening and treatment.

The Relationship Among Perceived Stress, Symptoms, and Inflammation in Persons With Inflammatory Bowel Disease.

OBJECTIVES:Previous studies have demonstrated that stress is associated with increased disease activity in individuals with inflammatory bowel disease (IBD). The association between perceived stress and gastrointestinal inflammation is not well described.METHODS:Participants were recruited from a population-based registry of individuals with known IBD. Symptomatic disease activity was assessed using validated clinical indices: the Manitoba IBD Index (MIBDI) and Harvey Bradshaw Index (HBI) for Crohn’s disease (CD), and Powell Tuck Index (PTI) for ulcerative colitis (UC). Perceived stress was measured using Cohen’s Perceived Stress Scale (CPSS). Intestinal inflammation was determined through measurement of fecal calprotectin (FCAL), with a level exceeding 250 μg/g indicating significant inflammation. Logistic regressions were used to evaluate the association between intestinal inflammation, perceived stress, and disease activity.RESULTS:Of the 478 participants with completed surveys and stool samples, perceived stress was associated with symptomatic activity (MIBDI) for both CD and UC (1.07 per 1-point increase on the CPSS, 95% confidence interval (CI) 1.03–1.10 and 1.03–1.11, respectively). There was no significant association between perceived stress and intestinal inflammation for either CD or UC. Active symptoms (MIBDI ≤3) were associated with intestinal inflammation in UC (odds ratio (OR) 3.94, 95% CI 1.65–9.43), but not in CD (OR 0.98, 95% CI 0.51–1.88).CONCLUSIONS:Symptomatic disease activity was unrelated to intestinal inflammation in CD and only weakly associated in UC. Although there was a strong relationship between perceived stress and gastrointestinal symptoms, perceived stress was unrelated to concurrent intestinal inflammation. Longitudinal investigation is required to determine the directionality of the relationship between perceived stress, inflammation, and symptoms in IBD.