Adjuvant therapy with antidepressants for the management of inflammatory bowel disease

BACKGROUND: Symptoms of anxiety and depression are common in inflammatory bowel disease (IBD). Antidepressants are taken by approximately 30% of people with IBD. However, there are no current guidelines on treating co-morbid anxiety and depression in people with IBD with antidepressants, nor are there clear data on the role of antidepressants in managing physical symptoms of IBD. OBJECTIVES: The objectives were to assess the efficacy and safety of antidepressants for treating anxiety and depression in IBD, and to assess the effects of antidepressants on quality of life (QoL) and managing disease activity in IBD. SEARCH METHODS: We searched MEDLINE; Embase, CINAHL, PsycINFO, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to 23 August 2018. Reference lists, trials registers, conference proceedings and grey literature were also searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) and observational studies comparing any type of antidepressant to placebo, no treatment or an active therapy for IBD were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. We used the Newcastle-Ottawa Scale to assess quality of observational studies. GRADE was used to evaluate the certainty of the evidence supporting the outcomes. Primary outcomes included anxiety and depression. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS) or the Hamilton Anxiety Rating Scale (HARS). Depression was assessed using HADS or the Beck Depression Inventory. Secondary outcomes included adverse events (AEs), serious AEs, withdrawal due to AEs, quality of life (QoL), clinical remission, relapse, pain, hospital admissions, surgery, and need for steroid treatment. QoL was assessed using the WHO-QOL-BREF questionnaire. We calculated the risk ratio (RR) and corresponding 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) with 95% CI. A fixed-effect model was used for analysis. MAIN RESULTS: We included four studies (188 participants). Two studies were double-blind RCTs, one was a non-randomised controlled trial, and one was an observational retrospective case-matched study. The age of participants ranged from 27 to 37.8 years. In three studies participants had quiescent IBD and in one study participants had active or quiescent IBD. Participants in one study had co-morbid anxiety or depression. One study used duloxetine (60 mg daily), one study used fluoxetine (20 mg daily), one study used tianeptine (36 mg daily), and one study used various antidepressants in clinical ranges. Three studies had placebo controls and one study had a no treatment control group. One RCT was rated as low risk of bias and the other was rated as high risk of bias (incomplete outcome data). The non-randomised controlled trial was rated as high risk of bias (random sequence generation, allocation concealment, blinding). The observational study was rated as high methodological quality, but is still considered to be at high risk of bias given its observational design.The effect of antidepressants on anxiety and depression is uncertain. At 12 weeks, the mean anxiety score in antidepressant participants was 6.11 + 3 compared to 8.5 + 3.45 in placebo participants (MD -2.39, 95% -4.30 to -0.48, 44 participants, low certainty evidence). At 12 months, the mean anxiety score in antidepressant participants was 3.8 + 2.5 compared to 4.2 + 4.9 in placebo participants (MD -0.40, 95% -3.47 to 2.67, 26 participants; low certainty evidence). At 12 weeks, the mean depression score in antidepressant participants was 7.47 + 2.42 compared to 10.5 + 3.57 in placebo participants (MD -3.03, 95% CI -4.83 to -1.23, 44 participants; low certainty evidence). At 12 months, the mean depression score in antidepressant participants was 2.9 + 2.8 compared to 3.1 + 3.4 in placebo participants (MD -0.20, 95% -2.62 to 2.22, 26 participants; low certainty evidence).The effect of antidepressants on AEs is uncertain. Fifty-seven per cent (8/14) of antidepressant participants group reported AEs versus 25% (3/12) of placebo participants (RR 2.29, 95% CI 0.78 to 6.73, low certainty evidence). Commonly reported AEs include nausea, headache, dizziness, drowsiness, sexual problems, insomnia, fatigue, low mood/anxiety, dry mouth, muscle spasms and hot flushes. None of the included studies reported any serious AEs. None of the included studies reported on pain.One study (44 participants) reported on QoL at 12 weeks and another study (26 participants) reported on QoL at 12 months. Physical, Psychological, Social and Environmental QoL were improved at 12 weeks compared to placebo (all low certainty evidence). There were no group differences in QoL at 12 months (all low certainty evidence). The effect of antidepressants on maintenance of clinical remission and endoscopic relapse is uncertain. At 12 months, 64% (9/14) of participants in the antidepressant group maintained clinical remission compared to 67% (8/12) of placebo participants (RR 0.96, 95% CI 0.55 to 1.69; low certainty evidence). At 12 months, none (0/30) of participants in the antidepressant group had endoscopic relapse compared to 10% (3/30) of placebo participants (RR 0.14, 95% CI 0.01 to 2.65; very low certainty evidence). AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the efficacy and safety of antidepressants in IBD can be drawn. Future studies should employ RCT designs, with a longer follow-up and develop solutions to address attrition. Inclusion of objective markers of disease activity is strongly recommended as is testing antidepressants from different classes, as at present it is unclear if any antidepressant (or class thereof) has differential efficacy

Systematic review with meta-analysis: the impact of a depressive state on disease course in adult inflammatory bowel disease

Background Despite a higher prevalence of psychosocial morbidity in Inflammatory Bowel Disease (IBD), the association between depressive state and disease course in IBD is poorly understood. Aim To investigate the impact of depressive state on disease course in IBD. Methods We conducted a systematic review in MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and PsychINFO for prospective studies evaluating the impact of baseline depressive state on subsequent disease course in adult IBD. Results Eleven studies matched our entry criteria, representing 3194 patients with IBD. Three reported on patients with ulcerative colitis (UC), four included patients with Crohn's disease (CD) exclusively, and four studies included both UC and CD. Five studies reported an association between depressive state and disease course. None of the UC‐specific studies found any association. In three of four CD‐specific studies, a relationship between depressive state and worsening disease course was found. In four of five studies including patients in remission at baseline, no association between depressive state and disease course was found. Pooled analysis of IBD studies with patients in clinical remission at baseline identified no association between depressive state and disease course (HR 1.04, 95%CI: 0.97‐1.12). Conclusion There is limited evidence to support an association between depressive state and subsequent deterioration in disease course in IBD, but what data that exist are more supportive of an association with CD than UC. Baseline disease activity may be an important factor in this relationship. Further studies are needed to understand the relationship between mental health and outcomes in IBD

Physical activity habits, limitations and predictors in people with inflammatory bowel disease: a large cross-sectional online survey

Background: Limited evidence suggests that physical activity has beneficial effects in people with inflammatory bowel disease (IBD). This study aimed to determine the physical activity habits of adults with IBD, the limitations to physical activity they experience because of their disease, and the extent to which their physical activity is affected by various demographic, clinical, and psychological factors. Methods: Data were collected on 859 adult participants (52% with Crohn's disease, 75% women) through an online survey conducted between May and June 2016. Measures included physical activity (International Physical Activity Questionnaire), psychological symptoms (Hospital Anxiety and Depression Scale), fatigue (subitems of IBD fatigue scale), exercise perceptions (Exercise Benefits/Barriers Scale), and disease activity. Regression analyses were used to identify predictors of physical activity. Results: Only 17% of respondents were categorized as "high active." Self-reported physical activity levels decreased, and fatigue and psychological scores increased, with increasing disease activity. Walking was the most common activity performed (57% of respondents) and running/jogging the most commonly avoided (34%). Many participants (n = 677) reported that IBD limited their physical activity, for reasons including abdominal/joint pain (70%), fatigue/tiredness (69%), disease flare-up (63%), and increased toilet urgency (61%). Physical activity was independently associated with depression, disease activity, and perceived barriers to exercise in people with Crohn's disease, and depression and age in people with ulcerative or indeterminate colitis (all P <= 0.038). Conclusions: This survey highlights several important factors that should be considered by designers of future physical activity interventions for people with IBD

Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease.

BACKGROUND & AIMS: We examined the relationship between symptoms of depression and anxiety and clinical recurrence of inflammatory bowel disease (IBD) in a large patient cohort. We considered the progression of depression and anxiety over time. METHODS: We collected clinical and treatment data on 2007 adult participants in an IBD study (56% with Crohn's disease [CD], 48% male) performed in Switzerland from 2006 through 2015. Depression and anxiety symptoms were quantified by using the Hospital Anxiety and Depression Scale. The relationship between depression and anxiety scores and clinical recurrence was analyzed by using survival-time techniques. RESULTS: We found a significant association between symptoms of depression and clinical recurrence over time (for all patients with IBD, P = .000001; for subjects with CD, P = .0007; for subjects with ulcerative colitis, P = .005). There was also a significant relationship between symptoms of anxiety and clinical recurrence over time in all subjects with IBD (P = .0014) and in subjects with CD (P = .031) but not ulcerative colitis (P = .066). CONCLUSIONS: In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment

Doctor communication quality and friends' attitudes influence complementary medicine use in inflammatory bowel disease

AIM: To examine the frequency of regular complementary and alternative therapy (CAM) use in three Australian cohorts of contrasting care setting and geography, and identify independent attitudinal and psychological predictors of CAM use across all cohorts. METHODS: A cross sectional questionnaire was administered to inflammatory bowel disease (IBD) patients in 3 separate cohorts which differed by geographical region and care setting. Demographics and frequency of regular CAM use were assessed, along with attitudes towards IBD medication and psychological parameters such as anxiety, depression, personality traits and quality of life (QOL), and compared across cohorts. Independent attitudinal and psychological predictors of CAM use were determined using binary logistic regression analysis. RESULTS: In 473 respondents (mean age 50.3 years, 60.2% female) regular CAM use was reported by 45.4%, and did not vary between cohorts. Only 54.1% of users disclosed CAM use to their doctor. Independent predictors of CAM use which confirm those reported previously were: covert conventional medication dose reduction (P < 0.001), seeking psychological treatment (P < 0.001), adverse effects of conventional medication (P = 0.043), and higher QOL (P < 0.001). Newly identified predictors were CAM use by family or friends (P < 0.001), dissatisfaction with patient-doctor communication (P < 0.001), and lower depression scores (P < 0.001). CONCLUSION: In addition to previously identified predictors of CAM use, these data show that physician attention to communication and the patient-doctor relationship is important as these factors influence CAM use. Patient reluctance to discuss CAM with physicians may promote greater reliance on social contacts to influence CAM decisions.Réme Mountifield, Jane M Andrews, Antonina Mikocka-Walus and Peter Bampto

Experience with and attitudes towards psychotherapy and antidepressants among patients with inflammatory bowel disease and functional gastrointestinal disorders : An online patient survey to inform system design

This study aimed to explore and compare experiences with and attitudes toward psychotherapy and antidepressants of patients with inflammatory bowel disease (IBD) and functional gastrointestinal disorders (FGiDs). Patients from gastroenterology clinic databases were invited to an online survey. Student\u27s t test, Mann-Whitney U test, chi-square test, and Fisher\u27s test were used to compare patients with IBD and FGiD on demographics and variables of interest. Of 86 participants, 56 (65%) had IBD and 30 (35%) had FGiDs. Mean levels of anxiety, depressive, and stress symptoms were within the moderate to severe range. Psychological care and antidepressants were offered to significantly more FGiD than to IBD respondents (37% vs. 9%; p = .009). Although the symptoms were generally reduced after the prescription of antidepressants, only 30% of IBD respondents and 21% of FGiD respondents using antidepressants would recommend them to others. In contrast, 53% of IBD respondents and 69% of FGiD respondents who used psychotherapy would recommend it to others. Both these therapies were valued by recipients; however, neither was reported to improve gastrointestinal (GI) symptoms. Given the high desire for and positive experiences of psychological care for these 2 common GI conditions, access to formal psychological support services within GI clinics would appear to be the most efficient model

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 Crohn's 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 treatmen

Does Computerized Cognitive Behavioral Therapy Help People with Inflammatory Bowel Disease? : A Randomized Controlled Trial

BACKGROUND: Cognitive behavioral therapy may be useful for improving health-related quality of life (HRQOL) of at least some patients with inflammatory bowel disease (IBD), especially those with psychiatric comorbidities. However, cognitive behavioral therapy can be difficult to access. These difficulties can be overcome by computerized cognitive behavioral therapy (CCBT). This is a randomized controlled trial of a self-administered CCBT intervention for patients with IBD focused on improving HRQOL. It is hypothesized that CCBT completers will have an improved HRQOL relative to people not allocated to CCBT. METHODS: Patients with IBD were randomly allocated to CCBT (n = 113) versus treatment as usual (n = 86). The IBD Questionnaire at 12 weeks after baseline was the primary outcome, while generic HRQOL, anxiety, depression, coping strategies, perceived stress, and IBD symptoms were secondary outcomes. Outcomes were also measured at 6 months after baseline. Predictors of dropout were also determined. RESULTS: Twenty-nine CCBT participants (25.7%) completed the CCBT. The IBD Questionnaire was significantly increased at 12 weeks in CCBT completers compared with treatment-as-usual patients (F = 6.38, P = 0.01). Short Form-12 mental score (F = 5.00, P = 0.03) was also significantly better in CCBT compared with treatment-as-usual patients at 12 weeks. These outcomes were not maintained at 6 months. The predictors of dropout were baseline depression, biological use, lower IBD Questionnaire scores, and not having steroids. CONCLUSIONS: Improvements at 12 weeks after baseline were not maintained at 6 months. Future research should aim to improve adherence rates. Moreover, CCBT may not work for patients with IBD with comorbid depression

Patient satisfaction with treatment for alcohol use disorders: comparing patients with and without severe mental health symptoms

BACKGROUND: Previous studies suggest patients with co-occurring alcohol use disorders (AUDs) and severe mental health symptoms (SMHS) are less satisfied with standard AUD treatment when compared to patients with an AUD alone. This study compared patient satisfaction with standard AUD treatment among patients with and without SMHS and explored how standard treatment might be improved to better address the needs of these patients. METHODS: Eighty-nine patients receiving treatment for an AUD either at an inpatient hospital, outpatient clinic, inpatient detoxification, or residential/therapeutic community services were surveyed. Patient satisfaction with treatment was assessed using the Treatment Perception Questionnaire (range: 0-40). Patients were stratified according to their score on the Depression Anxiety Stress Scale. Forty patients scored in the extremely severe range of depression (score &gt;14) and/or anxiety (score &gt;10) (indicating SMHS) and 49 patients did not. An inductive content analysis was also conducted on qualitative data relating to areas of service improvement. RESULTS: Patients with SMHS were found to be equally satisfied with treatment (mean =25.10, standard deviation =8.12) as patients with an AUD alone (mean =25.43, standard deviation =6.91). Analysis revealed that being an inpatient in hospital was associated with reduced treatment satisfaction. Patients with SMHS were found to be significantly less satisfied with staffs\u27 understanding of the type of help they wanted in treatment, when compared to patients with AUDs alone. Five areas for service improvement were identified, including staff qualities, informed care, treatment access and continuity, issues relating to inpatient stay, and addressing patients\u27 mental health needs. CONCLUSION: While findings suggest that AUD treatment services adequately meet the needs of patients with SMHS in treatment, patients with SMHS do feel that staff lack understanding of their treatment needs. Findings have important implications as to how current health care practice might be improved according to the patient\u27s perspective of care