Issue 01

Mentoring in IBD is an innovative and successful educational program for Canadian gastroenterologists that now includes an annual national meeting, regional satellites in both official languages, a website, an educational newsletter series, and regular electronic communications answering key clinical questions with new research. This issue is based on the presentation made by the issue editor, Dr Rebecca Anglin, at the annual national meeting, Mentoring in IBD XVI: The Master Class, held November 6, 2015 in Toronto, Ontario.

Patients with inflammatory bowel disease (IBD) have increased rates of depression and anxiety, with a lifetime prevalence approximately double that of the general population.(1,2) In some patients, coexisting psychiatric symptoms may affect the ability of some patients to cope with a chronic gastrointestinal illness, whereas in others depression and anxiety may develop as a result of their IBD. Recently there has also been interest in shared biological pathways that may contribute to both IBD and mental illness, including inflammatory pathways and the microbe-gut-brain axis. Mental health problems in patients with IBD are associated with a significant impact on quality of life, worse disease course, increased rates of treatment failure with medications, and elevated risk of surgery.(1–4)  It is therefore imperative to evaluate the mental health of patients with IBD and manage anxiety and depression in these patients appropriately.

The gut-brain axis

The gut and the brain are connected by multiple bidirectional pathways including neuronal, humoral and immune pathways (Figure 1). Although specific mechanisms have not been fully elucidated, emerging evidence suggests that inflammatory pathways and changes in the gut microbiome may contribute to a shared pathophysiology between mood and anxiety disorders and IBD.(5,6) The majority of the evidence supporting the involvement of the microbe-gut-brain axis in mental health originated in animal studies that have shown that altering the gut microbiome can cause changes in the brain and in behaviour. (7)

Figure 1. The gut-brain axis (7). Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Microbiology (The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol. 2012;10(11):735–42.), copyright 2012.

IBD and mental health

The majority of clinical and population-based studies show increased rates of anxiety and depression in patients with IBD. A cohort study conducted among patients with IBD (N=351) in Manitoba compared lifetime prevalence of mental health disorders in these patients with matched controls from a national survey (N=779).(1) The questionnaire-based study found significantly higher rates of major depression among patients with IBD (27.2%) than among controls (12.3%, odds ratio [OR] 2.20; 95% confidence interval [CI]: 1.64–2.95). Patients with major depression had a lower quality of life and earlier onset of IBD symptoms. About half of patients with a mood disorder experienced the first episode of depression more than 2 years before the onset of IBD.

In addition, mental health can have significant effects on IBD symptoms and disease course. A prospective, longitudinal, observational study (N=60) enrolled patients with clinically inactive IBD and followed them for 18 months after a disease flare.(8) Depression was present in 28% of patients at baseline, and 59% of patients had at least one IBD relapse during follow-up. Depression scores at baseline were significantly (P<.01) correlated with the total number of relapses during this time and with the time to first relapse (P<.05). More frequent relapses were also correlated with anxiety (P<.05) and low health-related quality of life (P<.01). Major depressive disorder was also a risk factor for failure to achieve remission with infliximab.

A multicentre electronic medical record-based cohort study of patients with Crohn’s disease (CD, n=5405) and ulcerative colitis (UC, n=5429) assessed the effect of mood disorders on the risk of subsequent surgery or hospitalization and on healthcare utilization.(9) One-fifth of the cohort had either major depressive disorder or generalized anxiety. Among patients with psychiatric comorbidity, multivariate analysis found a 28% greater risk of surgery in patients with CD (OR: 1.28, 95% CI: 1.03–1.57), but not UC. Increased healthcare utilization was seen in patients with psychiatric comorbidity.

Stress and IBD

A population-based IBD research registry assessed triggers of IBD flares using surveys performed at baseline and every 3 months for 1 year.(10) The baseline survey was completed by 704 individuals with IBD, and all 5 surveys were completed by 552 individuals (78.3%). The 174 patients who had a flare were compared with 209 patients without flare. Multivariate analysis found the only trigger significantly associated with flare was perceived stress (adjusted OR: 2.40, 95% CI: 1.35–4.26).

A study using a population-based registry of individuals with known IBD assessed symptomatic disease activity, fecal calprotectin, and perceived stress in 478 individuals.(11) Perceived stress was significantly associated with IBD symptoms but not with intestinal inflammation. Stressful life events predicted flare in the next 3 months.

Screening for depression and anxiety in patients with IBD

The significant impact of mental health on IBD makes it important for gastroenterologists to be aware of simple validated screening tools for anxiety and depression (3), mental health resources available in their community, and how to make appropriate mental health referrals.

Recognizing symptoms

Symptoms of depression include a sad or depressed mood; loss of interest in normal activities; feelings of guilt, worthlessness, and hopelessness; problems with neurovegetative symptoms, such as problems with sleep or appetite; and suicidal ideation. For a diagnosis of depression, symptoms must persist for at least 2 weeks and interfere with functioning.(12) As many patients with IBD already have problems with neurovegetative symptoms, it is more helpful to focus on mood-related symptoms, loss of interest, and hopelessness when screening for depression. Symptoms of a clinical anxiety disorder include excessive worries about the future, avoidance of feared situations, and physiological arousal. In all patients in whom depression or anxiety is suspected, their acute safety and suicidal ideation should be evaluated.

Screening tools

A variety of screening tools are available in clinical practice to assess anxiety and depression in patients with IBD.

Patient Health Questionnaire for Depression and Anxiety (the PHQ-4)

The PHQ4 is an ultra-brief screening scale for depression and anxiety; increasing scores are strongly associated with functional impairment, disability days, and healthcare use.(13) The PHQ-4 asks the following question: Over the past 2 weeks, how often have you been bothered by the following problems?

●  Feeling nervous, anxious or on edge

●  Not being able to stop or control worrying

●  Little interest or pleasure in doing things

●  Feeling down, depressed, or hopeless

Response choices are not at all, several days, more than half the days, and nearly every day.

Luebeck Interview for Psychosocial Screening (LIPS-IBD)

This rating tool takes about 10 minutes to administer and uses a 5-point Likert scale to assess depression, anxiety, social support, impact of the disease, global level of psychosocial stress, and demand for psychosocial support in patients with IBD.(14) The LIPS-IBD is suitable for use in clinical practice and has the advantage of being designed for use in patients with IBD.

Hospital Anxiety and Depression Scale (HADS)

HADS is a self-assessment tool that patients can complete in the waiting room in just a few minutes. The tool asks patients to rate the frequency of a variety of emotions during the past week.(15) Each item on the questionnaire is scored from 0 to 3. HADS has been found to be reliable in detecting depression and anxiety and identifying its severity in patients with coexisting medical illness.

Incorporating screening into clinical practice

Patients may not spontaneously bring up problems with mood and anxiety, and it is important that physicians ensure they specifically review mental health with their IBD patients. Having a good relationship with the patient is critical to being able to talk about mental health issues, but discussing a patient’s emotional state does not have to be challenging or time consuming. Simply acknowledging that living with IBD can be difficult allows the clinician to open the discussion and validates the patient’s experience. Using the right language is important. Examples of questions are the following

●  Have you been having difficulty with stress or worry?

●  Have you been feeling anxious, tense, or on edge much of the time?

●  Have you felt down or depressed most of the day?

●  Have you lost interest in most things or find you just don’t enjoy things lately?

It is useful to screen all patients for mood and anxiety disorders at initial diagnosis, at times when their disease is active, when symptoms prove refractory despite adequate therapy and absence of disease activity, and when the patient presentation suggests anxiety or depression. Routine screening can also be considered. Simply asking how the patient is coping may initiate discussion in patients experiencing difficulties. Alternatively, clinicians may find it helpful to incorporate use of a self-administered screening tool into clinic appointments.

Treatment of mental health disorders in patients with IBD

Treatment of patients with IBD and psychiatric comorbidity may include pharmacotherapy, psychotherapy, or a combination of modalities. Unfortunately, there is a paucity of well-designed randomized controlled trials of antidepressants in patients with IBD. A systematic review of antidepressant therapy in patients with IBD identified 12 publications of nonrandomized studies.(16) The review found a general lack of reliable data to determine the efficacy of antidepressants in patients with IBD, although most articles suggested antidepressants were beneficial.

In clinical practice we tend to extrapolate from the data on treating anxiety and depression in general when treating patients with IBD and psychiatric comorbidity. First-line pharmacological agents generally include selective serotonin reuptake inhibitors, selective serotonin and noradrenaline reuptake inhibitors, and newer agents. Treatment selection is guided by previous response, comorbidity, symptom profile, patient preference, tolerability, cost, and the potential for drug-drug interactions. Although tricyclic medications are generally considered second-line agents in the treatment of depression and anxiety, they are sometimes used more frequently in patients with IBD, given their potential to cause constipation.

A systematic review of randomized controlled trials of psychotherapy in patients with IBD identified 18 studies reported in 19 papers.(17) The review found that psychotherapy had minimal effect on anxiety, depression, or quality of life, although it may have had an impact on pain, fatigue, relapse, hospitalization, and medication adherence. Higher-quality evidence is needed in this patient population. Psychotherapy, which has significant efficacy in anxiety and depression, should be discussed with patients with IBD and psychiatric comorbidity when it is available. Access to psychotherapy, the need to attend weekly sessions, and cost can be significant barriers for patients with IBD. As a result, there is emerging interest in the use of electronic platforms for psychotherapy in this population.

Risk stratification of patients, based on severity and any acute safety concerns, is an essential component of evaluating patients with IBD and concurrent anxiety or depression. It is important to address any perceived stigma associated with mental illness by explaining how common these conditions are in patients with IBD and their negative effect on disease symptoms, functioning, quality of life, and overall health. It is also important to determine patient preference for pharmacotherapy or psychotherapy and to identify the available options, which include initiating pharmacotherapy or referring the patient back to the primary care physician or to a mental health professional for treatment. It is therefore critical to determine your comfort level and that of the patient’s primary care physician in treating psychiatric illness and to identify mental health resources in your community. Many primary care physicians are very comfortable dealing with mental health problems, as these issues are a common presenting problem in that setting. In addition, the greatest current gap in care is access to mental health resources. Optimal management would be comanagement between gastroenterology and psychiatry, but this model has yet to be developed in most centres.

Conclusion

A complex relationship exists between mental health and IBD, with each condition potentially influencing the other. Chronic illness is known to influence psychological well-being, and mental health affects IBD disease activity, patient functioning, and quality of life. It is important to screen patients for anxiety and depression and refer them for appropriate management when indicated.

Clinical Case

Case presentation

Leanne is a 19-year-old female with documented severe colonic Crohn’s disease (CD) diagnosed 5 years ago. She is being treated with mesalamine and azathioprine. At her last visit, 2 years ago, her symptoms were minimal, C-reactive protein (CRP) and fecal calprotectin (FCP) had normalized, and you felt the disease was in remission. Leanne did not keep the last 2 office visits your secretary booked with her. In addition, she has not had any screening blood tests while on azathioprine, despite being sent multiple requisitions via email and regular mail.

Case evolution

Today, Leanne is in your office for the first time in 2 years, complaining of recurrent central abdominal pain and diarrhea (10 times daily with no blood) for the past 6 months. She has no other constitutional symptoms. When you ask Leanne about her life, she tells you she has dropped out of college and moved back to her parents’ home, where she is living in the basement. She says that she recently lost a volunteer position at the local cancer centre.

Gastroscopy and colonoscopy show no active disease, and both CRP and FCP are normal. At the follow-up appointment the next day, she continues to complain of significant abdominal pain and diarrhea. Pharmacy records indicate Leanne is getting oxycodone from 5 different physicians, up to 100 pills per week. She tells you her father has metastatic oral carcinoma and she is having difficulty controlling her anxiety about what will happen to him. Leanne says she is sleeping only a few hours a night and has lost her motivation to go back to school. She has also withdrawn from her friends. When confronted, she denies using oxycodone and bursts into tears when you try to discuss her father.

You refer Leanne for psychiatric consultation. She is diagnosed with major depressive disorder, generalized anxiety disorder, and oxycodone use disorder and receives treatment.

Commentary

In this case a young patient with previously well-controlled IBD became noncompliant with testing and started missing appointments. This would have been an ideal time to try to schedule an appointment with the patient and screen for any underlying mental health concerns. When the patient subsequently presented with increased symptoms, it was very appropriate to assess her disease activity. Given her considerable stressors, screening for anxiety and depression should have also been performed. The presence of active symptoms in the absence of disease activity should again have triggered evaluation for depression and anxiety, particularly in light of her increased psychosocial stressors. The fact she has dropped out of school and recently lost a volunteer position suggests social withdrawal, loss of interest and motivation, and impaired functioning secondary to anxiety and/or depression. Finally it emerges that Leanne also has an opiate use disorder which demands intervention. She is also coping with her father’s illness; experiencing anxiety, decreased sleep, impaired motivation, and withdrawal; and becomes tearful.

At this time, further exploration of her depressive and anxious symptoms, suicidal ideation, and acute risks should be undertaken. In collaboration with her family physician, psychiatric consultation should be arranged, as was done in this case. Ideally she would be followed by a psychiatrist or other mental health professional in close collaboration with her family physician and gastroenterologist, with regular communication. Treatment may involve pharmacologic and nonpharmacologic interventions. Over time it will be important for the gastroenterologist to remain involved in the case to ensure her gastrointestinal symptoms improve with cessation of opiate use and treatment of her anxiety and depression. Her IBD disease activity will also need to be monitored, together with other contributors to her symptoms.

References

1. Walker JR, Ediger JP, Graff LA, et al. The Manitoba IBD cohort study: a population-based study of the prevalence of lifetime and 12-month anxiety and mood disorders. Am J Gastroenterol. 2008;103(8): 989–97.
2. Fuller-Thomson E, Sulman J. Depression and inflammatory bowel disease: findings from two nationally representative Canadian surveys. Inflamm Bowel Dis. 2006;12(8):697–707.
3. Graff LA, Walker JR, Bernstein CN. Depression and anxiety in inflammatory bowel disease: a review of comorbidity and management. Inflamm Bowel Dis. 2009;15(7):1105–18.
4. Guthrie E, Jackson J, Shaffer J, et al. Psychological disorder and severity of inflammatory bowel disease predict health-related quality of life in ulcerative colitis and Crohn’s disease. Am J Gastroenterol. 2002;97(8):1994–9.
5. Anglin R, Surette M, Moayyedi P, et al. Lost in translation: the gut microbiota in psychiatric illness. Can J Psychiatry. 2015;60(10):460–3.
6. Anglin R, Libertucci J, Moayyedi P, et al. The gut microbiome in patients with anxiety, depression and inflammatory bowel disease. Poster at the 53^rd Annual Meeting of the American College of Neuropsychopharmacology; December 8, 2014; Phoenix, AZ.
7. Collins SM, Surette M, Bercik P. The interplay between the intestinal microbiota and the brain.Nat Rev Microbiol. 2012;10(11):735–
8. Mittermaier C, Dejaco C, Waldhoer T, et al. Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study. Psychosom Med. 2004;66(1):79–
9. Ananthakrishnan AN, Gainer VS, Perez RG, et al. Psychiatric co-morbidity is associated with increased risk of surgery in Crohn’s disease. Aliment Pharmacol Ther. 2013;37(4):445–
10. Bernstein CN, Singh S, Graff LA, et al. A prospective population-based study of triggers of symptomatic flares in IBD. Am J Gastroenterol. 2010;105(9):1994–
11. Targownik LE, Sexton KA, Bernstein MT, et al. The relationship among perceived stress, symptoms, and inflammation in persons with inflammatory bowel disease. Am J Gastroenterol. 2015;110(7):1001–
12. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5. Arlington, VA: American Psychiatric Association Publishing; 2013.
13. Kroenke K, Spitzer RL, Williams JB, et al. An ultra-brief screening scale for anxiety and depression: the PHQ-4. Psychosomatics. 2009;50(6):613–
14. Kunzendorf S, Jantschek G, Straubinger K, et al. The Luebeck interview for psychosocial screening in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2007;13(1):33–
15. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–
16. Mikocka-Walus, AA, Turnbull DA, Moulding NT, et al. Antidepressants and inflammatory bowel disease: a systematic review. Clin Pract Epidemiol Ment Health. 2006;2(24).
17. McCombie AM, Mulder RT, Gearry RB. Psychotherapy for inflammatory bowel disease: a review and update. J Crohns Colitis. 2013;7(12):935–49

Editor-in-Chief

 John K. Marshall, MD MSc FRCPC AGAF, Chief of Gastroenterology Clinical Service, Hamilton Health Sciences; Professor of Medicine, Division of Gastroenterology, McMaster University , Hamilton, ON

Co-Editor-in-Chief

Richard N. Fedorak, MD FRCPC FRCP (London) FRCS, Dean, Faculty of Medicine & Dentistry; Professor of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB

Issue Editor

Rebecca Anglin, MD PhD FRCPC, Assistant Professor, McMaster University, Department of Psychiatry and Behavioural Neurosciences and, Department of Medicine, Division of Gastroenterology, McMaster University , Hamilton, ON

Mentoring in IBD Curriculum Steering Committee

 Alain Bitton, MD FRCPC, McGill University, Montreal, QC

Brian Bressler, MD MS FRCPC, University of British Columbia, Vancouver, BC

Anne M. Griffiths, MC FRCPC, University of Toronto, Toronto, ON

Steven E. Gruchy, MD MSc FRCPC, Dalhousie University, Halifax, ON

Remo Panaccione, MD FRCPC, University of Calgary, Calgary, AB

Craig Render, MD FRPCP, University of British Columbia, University of Alberta, Kelowna, BC

Hillary Steinhart, MD MSc FRCPC, University of Toronto, Toronto, ON

Jennifer Stretton, ACNP MN BScN, St. Joseph’s Healthcare, Hamilton, ON

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