FUNCTIONAL DISORDERS TREATMENT ADVANCES. Dr. Adriana Lazarescu MD FRCPC Director GI Motility Lab, Edmonton Associate Professor University of Alberta

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1 FUNCTIONAL DISORDERS TREATMENT ADVANCES Dr. Adriana Lazarescu MD FRCPC Director GI Motility Lab, Edmonton Associate Professor University of Alberta

2 Name: Dr. Adriana Lazarescu Conflict of Interest Disclosure (over the past 24 months) Commercial or Non-Profit Interest Allergan Relationship advisory board, speaker

3 Objectives At the end of this session, participants should be able to 1. Describe the role of centrally acting psychopharmacologic treatments for functional GI disorders 2. Recognize new and future management options for functional GI disorders

4 * * * CanMEDS Roles Covered Medical Expert (as Medical Experts, physicians integrate all of the CanMEDS Roles, applying medical knowledge, clinical skills, and professional values in their provision of high-quality and safe patient-centered care. Medical Expert is the central physician Role in the CanMEDS Framework and defines the physician s clinical scope of practice.) Communicator (as Communicators, physicians form relationships with patients and their families that facilitate the gathering and sharing of essential information for effective health care.) Collaborator (as Collaborators, physicians work effectively with other health care professionals to provide safe, highquality, patient-centred care.) Leader (as Leaders, physicians engage with others to contribute to a vision of a high-quality health care system and take responsibility for the delivery of excellent patient care through their activities as clinicians, administrators, scholars, or teachers.) Health Advocate (as Health Advocates, physicians contribute their expertise and influence as they work with communities or patient populations to improve health. They work with those they serve to determine and understand needs, speak on behalf of others when required, and support the mobilization of resources to effect change.) Scholar (as Scholars, physicians demonstrate a lifelong commitment to excellence in practice through continuous learning and by teaching others, evaluating evidence, and contributing to scholarship.) Professional (as Professionals, physicians are committed to the health and well-being of individual patients and society through ethical practice, high personal standards of behaviour, accountability to the profession and society, physician-led regulation, and maintenance of personal health.)

5 Common themes in functional GI disorders (FGID) PAIN PSYCHOSOCIAL COMORBIDITY

6 The brain-gut axis

7 Visceral hypersensitivity and/or central sensitization Multicomponent integration of nociceptive information Explains variability in the experience and reporting of pain CNS amplification of visceral signals is increased in psychologically distressed individuals

8 Impact of FGID 179 IBS patients (Rome III), 78% female Online research survey to assess Impact of IBS on daily activities Comorbid psychiatric diagnoses Symptom severity Quality of life Symptom-specific cognitive affective factors related to IBS Ballou S, Keefer L. Neurogastroenterol Motil (2017) 29(4) Epub

9 Impact of FGID

10 FGID Dysregulation of brain-gut modulation of pain Pain treatments targeted at the gut are often not as effective in patients with moderate to severe pain Centrally targeted therapies, including psychopharmacologic medications and behavioural treatments have been shown to help in chronic GI pain Ford AC et al. Gut (2009) 58:367-78

11 Conceptual model for the development of chronic abdominal pain Tornblom H, Drossman DA. Neurogastroenterol Motil (2015) 27(4):455-67

12 Neuromodulators

13 Rationale for use in FGID Treat comorbid psychological distress, anxiety, hypervigilence, selective attention and catastrophizing Treat psychiatric diagnoses, such as depression Reduce pain by downregulating incoming visceral signals Take advantage of side effects eg. TCA constipation for IBS- D, SSRI diarrhea for IBS-C OFF LABEL USE

14 Tricyclic antidepressants Side effects sedation, hypotension, QT interval prolongation, dry mouth, constipation If concomitant depression, higher dose required also increases side effects

15 Meta-analysis amitriptyline in IBS Chao G, Zhang S. Intern Med (2013) 52:419-24

16 SSRIs Better side effect profile Good for concurrent anxiety and depression, but work even if not present TCA>SSRI for functional dyspepsia

17 Influence of placebo or citalopram on the severity of abdominal pain (A), bloating (B), severity of stool pattern abnormalities (C), and on overall irritable bowel syndrome symptom severity (D). *p<0.05 compared with before treatment; p<0.05 compared with placebo. J Tack et al. Gut 2006;55: Copyright BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

18 Meta-analysis in IBS patients Ford AC et al. Am J Gastroenterology (2014) 109(9):

19 SNRIs Better side effect profile than TCAs Most studies from peripheral diabetic neuropathic pain, fibromyalgia Chial HJ et al. Am J Physiol Gastrointest Liver Physiol (2003) 284:G130-7

20 Tetracyclic antidepressant - mirtazapine Little data in other FGID than functional dyspepsia Tack J et al. Clin Gastroenterol Hepatol (2016) 14(3):385-92

21 Sobin WH et al. Am J Gastroenterol (2017) 112:

22 Psychological therapies in IBS Meta-analysis What works - CBT, hypnotherapy, multicomponent psychological therapy, multicomponent psychological therapy over the phone, dynamic psychotherapy What does not work?? self-administered/minimal contact CBT, CBT via internet, training or therapy, stress management, mindfulness meditation training Ford AC et al. Am J Gastroenterol (2014) 109(9):

23 Hypnotherapy First study in IBS in 1984 by Whorwell et al. in the Lancet Initially done in person with a trained gut-directed hypnotherapist, then continue daily at home with a recorded script A form of biofeedback

24 Hypnotherapy Lindfors P et al. Am J Gastroenterol (2012) 107:276-85

25 Limiting factors Lack of trained practitioners in gut-specific therapy and hypnotherapy Cost and coverage

26 Augmentation When monotherapy with TCA, SSRI or SNRI is not effective or not tolerated due to side effects Lower doses of two medications than when used individually or combine a medication with psychological therapy Aim for synergistic effect and less side effects

27 Putting it together Sperber AD, Drossman DA. Aliment Pharmacol Ther (2011) 33:514-24

28 Take Home Messages An important component of pain in FGID is centrallymediated Neuromodulators can play a role in management of pain in FGID choose based on psychiatric comorbidity and side effect profile Hypnotherapy can help with a variety of symptoms in FGID

29 Evaluation and Certificate of Attendance Please download the CDDW app to complete the session evaluation and to receive your certificate of attendance.

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