Chicken or Egg, Mental Health Disorders in Inflammatory Bowel Disease: Does It Matter?

Abstract

See “Relative contribution of disease activity and psychological health to prognosis of inflammatory bowel disease during 6.5 years of longitudinal follow-up,” by Fairbrass KM, Gracie DJ, Ford AC, et al, on page 190. See “Relative contribution of disease activity and psychological health to prognosis of inflammatory bowel disease during 6.5 years of longitudinal follow-up,” by Fairbrass KM, Gracie DJ, Ford AC, et al, on page 190. Depression and anxiety are common in patients with inflammatory bowel disease (IBD) with 49% and 26% of patients experiencing anxiety and depressive symptoms at the time of an initial visit to a tertiary referral center, respectively.1Faust A.H. Halpern L.F. Danoff-Burg S. et al.Psychosocial factors contributing to inflammatory bowel disease activity and health-related quality of Life.Gastroenterol Hepatol (N Y). 2012; 8: 173-181PubMed Google Scholar The prevalence of depression and anxiety is increasingly recognized by gastroenterologists and advanced practice providers. There is controversy as to whether depression and anxiety are a consequence of living with IBD or whether these disorders contribute to disease activity and poor outcomes.2Marrie R.A. Graff L.A. Fisk J.D. et al.The relationship between symptoms of depression and anxiety and disease activity in IBD over time.Inflamm Bowel Dis. 2021; 27: 1285-1293Crossref PubMed Scopus (25) Google Scholar,3Dolovich C. Bernstein C.N. Singh H. et al.Anxiety and depression leads to anti-tumor necrosis factor discontinuation in inflammatory bowel disease.Clin Gastroenterol Hepatol. 2021; 19: 1200-1208.e1Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar It is likely that both are true, and that the mind and body cannot be disentangled when managing IBD. In the study by Fairbrass et al4Fairbrass K.M. Gracie D.J. Ford A.C. Relative contribution of disease activity and psychological health to prognosis of inflammatory bowel disease during 6.5 years of longitudinal follow-up.Gastroenterology. 2022; 163: 190-203Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar in this issue of Gastroenterology, investigators from the IBD Clinic at St. James University Hospital in the UK assessed whether depression or anxiety increased the risk of relapse (including steroid use and escalation of medical therapy), IBD-related hospitalization, intestinal resection, and death in 760 well-characterized patients with IBD, followed prospectively for 6.5 years. Participants ≥16 years of age were evaluated at baseline for a common mental disorder (anxiety or depression) using the Hospital Anxiety and Depression Scale. Disease activity was assessed using the Harvey Bradshaw Index for Crohn’s disease and the Simple Clinical Colitis Activity Index for ulcerative colitis. Additionally, approximately 50% of the cohort provided a fecal calprotectin at baseline to assess for biologic activity. Overall, 54% of participants flared, 55% escalated medical therapy, 25% were hospitalized, 12% underwent an intestinal resection, and 6% died during the follow-up period. Compared with patients in clinical remission without depression or anxiety, patients with IBD symptoms and depression or anxiety were 2.4, 1.7, and 5.0 times more likely to receive steroids for a flare, escalate medical therapy, and die, respectively. The odds of requiring steroids and escalating therapy were similar between patients in clinical remission with depression/anxiety and those with bowel symptoms without depression or anxiety. When assessing patients based solely on the presence of biochemical disease activity, the associations between mental health and outcomes were even stronger. How should the IBD provider interpret and act on these findings? First, one should determine if the patients in this study are similar to those seen in your clinical practice. There are notable differences in the St. James population compared with other referral center populations, particularly in the United States. The rates of aminosalicylate and immune suppressant use (43%–50% and 32%–37%, respectively) were high and rates of anti-tumor necrosis factor use were low (15%–21%). Additionally, 34%–40% of patients had an elevated fecal calprotectin at baseline.4Fairbrass K.M. Gracie D.J. Ford A.C. Relative contribution of disease activity and psychological health to prognosis of inflammatory bowel disease during 6.5 years of longitudinal follow-up.Gastroenterology. 2022; 163: 190-203Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Does this finding suggest that the population was undertreated for their IBD? Unpublished data from 4369 participants in the Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) cohort (65% Crohn’s disease and 33% ulcerative colitis) reported that baseline biologic use was present in 68% of participants with over 50% of participants on anti-tumor necrosis factor therapy. Only 22% were on aminosalicylate therapy. Approximately 32% of participants were treated with steroids, 12% were hospitalized, 3% underwent a resection, and 0.6% died after enrollment. However, the mean follow-up time of this cohort was 1.8 years (range, 0–5.2 years). Does this factor suggest that more aggressive treatment of the underlying IBD would prevent a clinical relapse, regardless of underlying depressive and anxiety symptoms? As a gastroenterologist, one aspect of care that we can control (or attempt to control) is underlying disease activity; few practices have access to a social worker, psychologist, or psychiatrist.5Mikocka-Walus A. Prady S.L. Pollok J. et al.Adjuvant therapy with antidepressants for the management of inflammatory bowel disease.Cochrane Database Syst Rev. 2019; 4: CD012680PubMed Google Scholar,6Massuger W. Moore G.T.C. Andrews J.M. et al.Crohn's & Colitis Australia inflammatory bowel disease audit: measuring the quality of care in Australia.Intern Med J. 2019; 49: 859-866Crossref PubMed Scopus (19) Google Scholar Gastroenterologists should identify patients early in the disease course who would benefit from treatment with a biologic or small molecule and treat aggressively to induce clinical as well as biochemical and endoscopic remission. What else can a gastroenterologist do? Although integrative care models such as those in academic centers can be applied to manage the whole patient, including mental health, these models are not practical for widespread use.7Regueiro M. Click B. Anderson A. et al.Reduced unplanned care and disease activity and increased quality of life after patient enrollment in an inflammatory bowel disease medical home.Clin Gastroenterol Hepatol. 2018; 16: 1777-1785Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 8Keefer L. Doerfler B. Artz C. Optimizing management of Crohn's disease within a project management framework: results of a pilot study.Inflamm Bowel Dis. 2012; 18: 254-260Crossref PubMed Scopus (35) Google Scholar, 9Keefer L.G.K. Siganporia T. Tse S. et al.A resilience-based care coordination program has a positive and durable impact on health care utilization in inflammatory bowel diseases (IBD).Am J Gastroenterol. 2020; 115: 367-375PubMed Google Scholar We should at least screen for depression and anxiety in our practices and identify a local resource to manage those who screen positive for these disorders. Unfortunately, access to psychiatric care is a recognized challenge.10Cummings J.R. Allen L. Clennon J. et al.Geographic access to specialty mental health care across high- and low-income US communities.JAMA Psychiatry. 2017; 74: 476-484Crossref PubMed Scopus (66) Google Scholar Should gastroenterologists not only identify, but also treat mental health disorders? Many of us already prescribe antidepressants and neuromodulators for the management of chronic abdominal pain. Might we prescribe 1 or a few antidepressants in our practices for treatment of depression and anxiety and might these agents treat the underlying IBD? Should we identify an advanced practice provider with experience in primary care to take on this role? I do not have the answer, but it is clear from the results of this well-designed and -executed study that patients with mental health disorders are at an increased risk for poor outcomes. Treating both diseases—IBD and mental health disorders—is critical to improving our patient’s physical and mental health. Health psychologists and medical social workers working with people living with IBD will not be surprised by the results of the Fairbass study—patients with clinical depression and anxiety, albeit not formally diagnosed, had poorer IBD outcomes.4Fairbrass K.M. Gracie D.J. Ford A.C. Relative contribution of disease activity and psychological health to prognosis of inflammatory bowel disease during 6.5 years of longitudinal follow-up.Gastroenterology. 2022; 163: 190-203Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar We know that most patients develop mental health disorders after a diagnosis of IBD, which can even lead to suicide, especially if the disease is untreated or undertreated and clinical symptoms persist.11Ludvigsson J.F. Olen O. Larsson H. et al.Association between inflammatory bowel disease and psychiatric morbidity and suicide: a Swedish nationwide population-based cohort study with sibling comparisons.J Crohns Colitis. 2021; 15: 1824-1836Crossref PubMed Scopus (20) Google Scholar Undertreated inflammation, to Dr Cross’ earlier point, can worsen IBD symptoms and impact patient quality of life, lead to disability and work absenteeism or low presenteeism,12Sciberras M. Karmiris K. Nascimento C. et al.Mental health, work presenteeism and exercise in inflammatory bowel disease.J Crohns Colitis. 2022 mar 3; : jjac037Crossref PubMed Scopus (2) Google Scholar and, most relevant to the chicken–egg question, increases depression, also an inflammatory state.13Craig C.F. Filippone R.T. Stavely R. et al.Neuroinflammation as an etiological trigger for depression comorbid with inflammatory bowel disease.J Neuroinflammation. 2022; 19: 4Crossref PubMed Scopus (9) Google Scholar Although screening for comorbid mental health conditions is necessary given the association of depression and anxiety on disease outcomes, including flares, medication escalation, and perhaps even death, it is not sufficient. One limitation of the Hospital Anxiety and Depression Scale and other self-report screeners for depression and anxiety is that they do not consider the patient in context of their disease state (does endorsement of difficulty sleeping indicate depression or waking up with diarrhea during the night?) and tend to capture acute symptoms of depressed mood or anxiety (in the past week), and not the ups and downs that typically occur in IBD. I encourage all IBD providers, from physicians and advanced practice providers to nurses, pharmacists, physical therapists, dieticians, and mental health professionals, to have discussions early in the patient–provider relationship about the patient’s attitudes, beliefs, and behaviors about their diagnosis and treatment course, taking the time to address extraintestinal manifestations and psychosocial concerns such as fatigue, sexual dysfunction, chronic pain, sleep disturbance, and functional overlap14Keefer L. Bedell A. Norton C. et al.How should pain, fatigue, and emotional wellness be incorporated into treatment goals for optimal management of inflammatory bowel disease?.Gastroenterology. 2022; 162: 1439-1451Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar and to identify any risk factors for the development of depression or anxiety, referring when possible to psychosocial care as a part of proactive IBD care. Circling back to the chicken–egg, I would go so far to say that disease-interfering self-management behaviors, such as smoking and somatization, as seen in this study, as well as poor adherence, low disease knowledge, low disease acceptance or denial, poor communication or relationships with the care team, unplanned care, and poor follow-through with recommendations between provider visits, regardless of whether depression or anxiety is present, will forever keep the chicken and the egg question unanswered. The results published here are, in whole or part, based on the SPARC IBD cohort data obtained from the IBD Plexus program of the Crohn’s & Colitis Foundation. Relative Contribution of Disease Activity and Psychological Health to Prognosis of Inflammatory Bowel Disease During 6.5 Years of Longitudinal Follow-UpGastroenterologyVol. 163Issue 1PreviewWe studied relative contribution of psychological ill-health and inflammatory bowel disease activity to prognosis; patients with active disease and symptoms of a common mental disorder were more likely to experience adverse outcomes. Full-Text PDF Open Access