FUNCTIONAL DISORDERS TREATMENT ADVANCES

Dr. Adriana Lazarescu MD FRCPC

Director – GI Motility Lab, Edmonton Associate Professor – University of Alberta

Conflict of Interest Disclosure

(over the past 24 months) Commercial or Non-Profit Interest Relationship

Allergan advisory board, speaker

Name: Dr. Adriana Lazarescu

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

Objectives

* 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, high-quality, 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.)

CanMEDS Roles Covered

PAIN

PSYCHOSOCIAL COMORBIDITY

Common themes in functional GI disorders (FGID)

“The brain-gut axis”

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

• 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

Impact of FGID

Ballou S, Keefer L. Neurogastroenterol Motil (2017) 29(4) Epub

Impact of 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

FGID

Ford AC et al. Gut (2009) 58:367-78

Conceptual model for the development of chronic abdominal pain

Tornblom H, Drossman DA. Neurogastroenterol Motil (2015) 27(4):455-67

Neuromodulators

• Treat comorbid psychological distress, anxiety, hyper-vigilence, 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

Rationale for use in FGID

OFF LABEL USE

• Side effects – sedation, hypotension, QT interval prolongation, dry mouth, constipation

• If concomitant depression, higher dose required also increases side effects

Tricyclic antidepressants

Meta-analysis – amitriptyline in IBS

Chao G, Zhang S. Intern Med (2013) 52:419-24

• Better side effect profile

• Good for concurrent anxiety and depression, but work even if not present

• TCA>SSRI for functional dyspepsia

SSRIs

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;55:1095-1103

Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

Ford AC et al. Am J Gastroenterology (2014) 109(9):1350-65

Meta-analysis in IBS patients

• Better side effect profile than TCAs

• Most studies from peripheral diabetic neuropathic pain, fibromyalgia

SNRIs

Chial HJ et al. Am J Physiol Gastrointest Liver Physiol (2003) 284:G130-7

Tetracyclic antidepressant - mirtazapine

Tack J et al. Clin Gastroenterol Hepatol (2016) 14(3):385-92

• Little data in other FGID than functional dyspepsia

Sobin WH et al. Am J Gastroenterol (2017) 112:693-702

• 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

Psychological therapies in IBS

Ford AC et al. Am J Gastroenterol (2014) 109(9):1350-65

• 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

Hypnotherapy

Hypnotherapy

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

• Lack of trained practitioners in gut-specific therapy and hypnotherapy

• Cost and coverage

Limiting factors

• 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

Augmentation

Putting it together

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

• An important component of pain in FGID is centrally-mediated

• 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

Take Home Messages

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Evaluation and Certificate of Attendance