role of antidepressants in the management of inflammatory bowel disease (IBD): a short report on

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1 The role of antidepressants in the management of inflammatory bowel disease (IBD): a short report on a clinical case-note audit This is the peer reviewed author accepted manuscript (post print) version of a published work that appeared in final form in: Stewart, Benjamin J, Gordon, Andrea L, Mikocka-Walus, Antonia A & Andrews, Jane M 2012 'The role of antidepressants in the management of inflammatory bowel disease (IBD): a short report on a clinical case-note audit' Journal of psychosomatic research, vol. 72, no. 2, pp This output may not exactly replicate the final published authoritative version for which the publisher owns copyright. It is not the copy of record. This output may be used for non-commercial purposes. This version is licensed under a Creative Commons CC-BY-NC-ND 4.0 license ( The final definitive published version (version of record) is available at: Persistent link to the Research Outputs Repository record: General Rights: Copyright and moral rights for the publications made accessible in the Research Outputs Repository are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. Users may download and print one copy for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the persistent link identifying the publication in the Research Outputs Repository If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

2 The Library Educating Professionals, Creating and Applying Knowledge, Engaging our Communities NOTICE: this is the author s version of a work that was accepted for publication in Journal of psychosomatic research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of psychosomatic research vol. 72, no. 2, pp doi: /j.jpsychores

3 The role of antidepressants in the management of inflammatory bowel disease (IBD): A short report on a clinical case-note audit Running Head: Antidepressants and IBD School of Nursing and Midwifery, University of South Australia and Department of Gastroenterology and Hepatology, Royal Adelaide Hospital Antonina A. Mikocka-Walus 1,2*, MA(Psych), PhD; Andrea L. Gordon 1, BSc(Hon), PhD; Benjamin J. Stewart 1,2, BHSc(Hons); Jane M. Andrews 3,4, MBBS, PhD, FRACP 1 School of Nursing and Midwifery and Sansom Institute for Health Research, University of South Australia, Adelaide, Australia; 2 School of Psychology, University of Adelaide, Adelaide, Australia; 3 IBD Service, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia; 4 School of Medicine, University of Adelaide, Adelaide, SA, Australia *Corresponding author: Dr Antonina Mikocka-Walus Research Fellow School of Nursing and Midwifery University of South Australia Tel Fax antonina.mikocka-walus@unisa.edu.au 1

4 ABSTRACT Objective: Low quality studies indicate a possibly beneficial role for antidepressants in terms of disease course in IBD. However, no systematic studies exist in the area. Thus, this study sought to determine the frequency of use and types of antidepressants used in IBD patients and to collect data with respect to any effect of antidepressants on the course of IBD in a usual care setting. Method: A case note audit was conducted at an IBD Service in a public tertiary hospital. Included patients were those diagnosed with IBD by a gastroenterologist; on the IBD database; and have had contact with the IBD Service in the last 6 months. Descriptive statistics were used to summarise the data. Results: Overall, 313 patients were eligible and 287 had complete data. Overall, 51 (17.8%) patients were currently taking antidepressants and 71 (24.7%) previously received antidepressants. Eighty-three (28.9%) patients had used an antidepressant at some time. In terms of disease activity while on antidepressants, the majority of patients had inactive disease but presented with what were thought by their clinicians to be functional symptoms. Conclusion: Antidepressants are commonly prescribed in IBD patients. In our cohort, they appear to be mostly used for functional symptoms. The current data do not allow us to judge whether they improve IBD disease activity. Targeted studies are needed to answer this question and to improve practice and patient outcomes. Keywords: inflammatory bowel disease; antidepressants; case note audit; disease activity; mental health 2

5 INTRODUCTION Inflammatory bowel disease (IBD) is a group of chronic, relapsing inflammatory disorders of the gut, of which Crohn s disease (CD) and ulcerative colitis (UC) are the most common. Whilst the aetiology of IBD is unknown, genetic, immune and environmental factors are all implicated. Recently, a psycho-neuro-immunological view of IBD has developed due to intriguing observations, that psychological status directly influences inflammatory lesions in the gut. Ghia et al. (1) have shown that inducing depression in mice increased their susceptibility to spontaneous intestinal inflammation by interfering with tonic vagal inhibition of pro-inflammatory macrophages. Moreover, treating the depressed state (with antidepressants) was found to not only, restore vagal function but also to reduce the intestinal inflammation. More recently, the same group have demonstrated that in healthy mice in which colitis was chemically induced and then allowed to heal, inflammation was able to be later reactivated via the induction of depression (2). In humans with IBD, a recent large prospective study (n=704) (3) showed that, of a number of factors studied, only high perceived stress was associated with an increased risk of IBD relapse. Another research group observed significant short-term improvements in systemic and mucosal inflammation in the gut after gut-focused hypnotherapy in 17 patients with active IBD (4). However, with respect to antidepressants use in IBD, to date, there has been little formal research,. In a systematic review, it was observed that even though antidepressants appear to improve both mental and somatic status of IBD patients, the low quality of available studies makes it impossible to make a definitive statement on their efficacy (5). However, the most recent update to this systematic review (6) found that desipramine and fluoxetine reduced the severity of intestinal inflammation in animal models. In a subsequent qualitative interview study, gastroenterologists reported that antidepressants were successful in reducing pain, gut 3

6 irritability, and urgency of defecation (7). While such observations increase our confidence in extrapolating such effects to the human situation, more targeted human studies are needed. Thus, the aim of this study was to determine the frequency of use and types of antidepressants currently prescribed to IBD patients as well as to collect evidence with respect to any documented effect of antidepressants on the course of IBD. MATERIALS AND METHODS Design and Participants This study was a retrospective case-note audit. Patient details for the audit were collected from the IBD database at a large Australian tertiary public hospital. Patients were included in the case note audit if: 1) they had been diagnosed with IBD by a gastroenterologist; 2) were on the IBD database; 3) were in contact with IBD Service within the preceding 6 months. Procedure Case notes of eligible patients were manually searched for information on current and past exposure to antidepressants. Detailed demographic information was also obtained from the case notes. After completion of the data entry, data were reviewed and analysed. Outcome measures Outcome measures included frequency, type and outcome of antidepressant treatment in terms of IBD course. Analysis 4

7 Results of the case note audit were summarised using descriptive statistics. ETHICAL CONSIDERATIONS This study was approved by the Royal Adelaide Hospital and University of South Australia Research Ethics Committees. RESULTS There were 313 patients that had been in contact with the clinic in the last 6 months who consented to be involved in research studies and thus 313 case-notes were requested. Of these, 287 had complete data and were available in full to the researchers. Patient demographics are presented in Table 1. Current medication is reported in Table 2. Of 287 patients, 51 (17.8%) were currently taking antidepressants. Of the 287 patients, 71 (24.7%) received antidepressants in the past. Of the 71 patients receiving antidepressants in the past, 32 were not currently on an antidepressant. When these data are added to the number of patients currently taking antidepressants, 83 (28.9%) IBD patients in clinic had used an antidepressant in their lifetime. Data for patients currently on antidepressants Of the 51 patients on current antidepressant therapy, most were prescribed antidepressants for depression (45%) or a combined depression and anxiety disorder (23.5%). Only three patients were given antidepressants for somatic complaints such as colonic irritability, headaches and sleep problems. Most patients were treated with amitriptyline (21.5%), followed by sertraline (15.6%) and ecitalopram (11.7%). Overall, 24 (47%) patients were treated with Selective 5

8 Serotonin Reuptake Inhibitors (SSRI), 16 (31%) with Tricyclic Antidepressants and 10 (19.6%) with other types of antidepressants. In terms of disease activity while on antidepressants, 15 (29.4%) of 51 patients had inactive disease but presented with symptoms such as pain or diarrhoea, consistent with functional bowel disorders. Another 11 (21.5%) patients had full remission with no disease activity. Two (3.9%) patients had active disease. In the remaining 23 (45%) patients, no data were recorded which may arguably suggest the disease was stable/quiescent. Of 51 patients currently on antidepressants, 39 (76.4%) received the same or other antidepressant in the past. Past antidepressant use Of 71 patients with a history of antidepressant use, in 29 (40.8%) patients, antidepressants were prescribed for depression, in 13 (18.6%) for a combined anxiety and depression disorder, in 10 (14.3%) patients for somatic complaints such as GI symptoms, pain or sleep problems, and in three (4.3%) patients the antidepressant was given for anxiety. No data were available for the remaining 16 (22.5%) patients. Once again, the majority of patients received amitriptyline (17%), followed by citalopram (14%) and sertraline (13%). Overall, antidepressant use was reported 79 times in these patients; SSRIs 41 times, tricyclics 28 times and other antidepressants 10 times. In terms of IBD activity while on antidepressants, of 71 patients, 19 (26.7%) had inactive disease but presented with functional symptoms, 12 (16.9%) patients had active disease and 9 (12.6%) had inactive disease. Two relevant comments were made by clinicians with respect to disease activity and antidepressants. In one patient with long term active IBD, doxepin had 6

9 led to significant improvement in symptoms (reduced pain and improved sleep) and a reduction on a Harvey-Bradshaw index was observed from 9 before treatment to less than 4 in response to antidepressant treatment. In another patient with controlled IBD activity but some ongoing functional problems, ileostomy output and patient s general wellbeing improved after treatment with amitriptyline. DISCUSSION This study is one of only a few worldwide focused specifically on the use of antidepressants in patients with IBD. The strength of our data lays in the fact that all patients attending our unit within the last 6 months were included, which avoids many inclusion, participation and recall biases. The most significant finding of the study was that nearly 30% of IBD patients have taken antidepressants throughout their lifetime, with many of them taking these medications long-term. This rate is much higher than the one in the general population (approx. 8.5%) (8) and deserves attention from clinicians and researchers. Since antidepressant use is common in this population and there is a lack of good quality studies on the topic, research exploring their safety, acceptability and the effect on IBD activity is needed to improve the standard care. Another important finding is that the patients taking antidepressants generally tend to be those whom their clinicians have judged to have minimal IBD activity. However, the present study is unable to ascertain whether this is due to antidepressant treatment or other factors. In addition, a significant number of patients report functional problems consistent with irritable bowel syndrome. This corresponds with findings of our previous study on functional gastrointestinal disorders (FGiDs) in IBD (9), showing a high co-morbidity of IBD with FGiDs even in patients in IBD remission. Moreover more recent work (10) has shown a dose 7

10 effect of FGID for increased anxiety/depression and so these would seem to be an ideal group in whom to use psychological therapies. Another clearly observable trend was that although the most commonly prescribed antidepressant was amitriptyline, the majority of patients were treated with SSRIs and the most commonly reported reason for this treatment was depression or a combined anxiety and depressive disorder. In a number of cases, there was some reported somatic benefit observed by clinicians with better control of bowel symptoms and improvement in sleep. The latter finding is consistent with the findings of our interview study (7) where gastroenterologists reported somatic benefits of antidepressant treatment in their patients. The major limitation of this study is the retrospective nature of its design. However, the use of secondary data is crucial before undertaking expensive and time consuming controlled trials and may inform their conduct. In addition, it has long been established that paper records may be inaccurate and of low quality (11). Thus, it is possible that case notes may have underreported information relevant to this research and this problem may only be addressed by designing high quality prospective studies with adequate data reporting. ACKNOWLEDGEMENTS This study was funded from the University of South Australia, School of Nursing and Midwifery Research Grant Scheme Authors are unaware of any conflict of interest with respect to this study. REFERENCES 8

11 1. Ghia JE, Blennerhassett P, Collins SM. Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression. J Clin Invest Jun;118(6): Ghia JE, Blennerhassett P, Deng Y, Verdu EF, Khan WI, Collins SM. Reactivation of inflammatory bowel disease in a mouse model of depression. Gastroenterology Jun;136(7): e Bernstein CN, Singh S, Graff LA, Walker JR, Miller N, Cheang M. A prospective populationbased study of triggers of symptomatic flares in IBD. Am J Gastroenterol. Sep;105(9): Mawdsley JE, Jenkins DG, Macey MG, Langmead L, Rampton DS. The effect of hypnosis on systemic and rectal mucosal measures of inflammation in ulcerative colitis. Am J Gastroenterol Jun;103(6): Mikocka-Walus AA, Turnbull DA, Moulding NT, Wilson IG, Andrews JM, Holtmann GJ. Antidepressants and inflammatory bowel disease: a systematic review. Clin Pract Epidemol Ment Health Sep 20;2(1): Mikocka-Walus A, Clarke D, Gibson P. Can antidepressants influence the course of inflammatory bowel disease (IBD)? A current state of research. European Gastroeneterology and Hepatology Review. 2009;5(1): Mikocka-Walus A, Turnbull D, Moulding N, Wilson I, Andrews J, Holtmann G. "It doesn't do any harm, but patients feel better": a qualitative exploratory study on gastroenterologists' perspectives on the role of antidepressants in inflammatory bowel disease. BMC Gastroenterology. 2007;7(1): Stagnitti MN. Antidepressant Use in the U.S. Civilian Noninstitutionalized Population, Rockville, Md: Agency for Healthcare Research and Quality2005 Contract No.: # Mikocka-Walus AA, Turnbull DA, Andrews JM, Moulding NT, Holtmann GJ. The effect of functional gastrointestinal disorders on psychological comorbidity and quality of life in patients with inflammatory bowel disease. Aliment Pharmacol Ther Aug 15;28(4):

12 10. Bryant RV, van Langenberg DR, Holtmann GJ, Andrews JM. Functional Gastrointestinal Disorders in Inflammatory Bowel Disease: Impact on Quality of Life and Psychological Status. J Gastroenterol Hepatol Jan Mansfield BG. How bad are medical records? A review of the notes received by a practice. J R Coll Gen Pract Sep;36(290):

13 TABLES Table 1: Demographics of the sample (n=287) n (%) IBD type Crohn s disease 179 (62.4%) Ulcerative colitis 95 (33.1%) Indeterminate colitis 13 (4.5%) Sex Male 144 (50.2%) Marital status Married/de facto 134 (46.7%) Single 79 (27.5%) Smoking status Current smokers 45 (21%) Mean (SD) Age (in years) 47 (17) 1

14 Table 2: Medication use in current and past IBD antidepressant users Current antidepressant users Past antidepressant users n=71 n=51 n (%) 5-ASA 18 (35.2) 16 (22.5) Azathioprine 16 (31.3) 14 (19.7) Biological treatment 8 (15.6) 2 (2.8) Corticosteroids 7 (13.7) 14 (19.7) Metronidazol 2 (3.9) 2 (2.8) Salazopyrin 1 (1.9) 3 (4.2) Pain killers 5 (9.8) 9 (12.6) Benzodiazepines 7 (13.7) 12 (16.9) 2