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Centrally Acting Pharmacological Agents in FGIDs Working Team

Aim. To understand the physiological effects of psychotropic agents on GI pain (and other GI symptoms) in order to implement targeted treatments that will improve patient care.

Rationale. A major area in the care of patients with FGIDs involves treatment of gastrointestinal pain. The pathophysiological basis for this pain extends on a spectrum from increased peripheral signaling due to the effects of motility and visceral hypersensitivity to central pain due to inadequate downregulation of incoming visceral signals or central hypersensitivity. The latter is common in CNS generated pain such as centrally mediated abdominal pain or GI pain associated with other painful or psychiatric co-morbidities. The use of centrally targeted medications (psychotropics) including various classes of antidepressants, anxiolytics, the newer atypical antipsychotics, and alpha 2 ligand agents have been studied extensively in somatic pain syndromes including peripheral neuropathy, migraine headache, fibromyalgia and musculoskeletal pain, and have shown benefit. However, to date investigation of psychotropics has been very limited within gastroenterology, and the clinical application of these agents within gastroenterology clinical practice lacks sophistication, precision and specificity. In fact most gastroenterologists use very low doses of tricyclics or SSRIs with limited understanding of targeted effects, proper dose or proper selection of medication. Furthermore there are very little data available on the differential effects of psychotropics on specific types of GI symptom (i.e. epigastric pain, pain in IBS, abdominal bloating, early satiation, belching, nausea, and non-cardiac chest pain) and no psychotropic agent has been approved by a regulatory agency for these disorders. Clearly there is a gap need to understand the role of psychotropic agents in GI pain and other functional GI symptoms in order to influence research, acceptance by industry and regulatory agencies and their use clinically among patients.

The objectives of this working team will be to:

  1. Review the literature in psychiatry, medicine and gastroenterology with regard to their physiological effects on the brain and the gut
  2. Review available studies specifically on the treatment of GI pain, other functional gastrointestinal symptoms and somatic syndromes with regard to their overall efficacy and selective value over other treatments
  3. Understand differential actions of psychotropic medications (e.g., SSRI, SNRI. TCA, atypicals, etc.) on GI pain and gastrointestinal function
  4. Identify GI and other adverse events and side effects of the various agents.
  5. Provide recommendations on the selection of agents for various clinical profiles (e.g. IBS-D, C, functional dyspepsia, CVS, chest pain, nausea/vomiting/weight loss, etc.)
  6. Provide recommendations as to how treatment should be introduced to the patient through the use of effective communication skills to improve patient satisfaction, engagement in treatment, and adherence.
  7. Understand how opioid agents relative to non-opioid agents are used to manage pain in FGIDs.

Team members:
Douglas A. Drossman (Gastroenterology, Psychiatry/Psychosomatic Medicine)
Jan Tack (Gastroenterology, GI physiology)
Lukas Van Oudenhove (Psychiatry)
Hans Tornblom (Gastroenterology)
Alex Ford (Gastroenterology – Meta-analysis)
Eva Szigethy (Psychiatry)
Psychopharmacologist (TBD)

Douglas A. Drossman, MD

Jan Tack, MD, PhD

Jan Tack, MD, PhD


Abstract:
Background & Aims
Central neuromodulators (antidepressants, antipsychotics, and other central nervous system−targeted medications) are increasingly used for treatment of functional gastrointestinal disorders (FGIDs), now recognized as disorders of gut−brain interaction. However, the available evidence and guidance for the use of central neuromodulators in these conditions is scanty and incomplete. In this Rome Foundation Working Team report, a multidisciplinary team summarized available research evidence and clinical experience to provide guidance and treatment recommendations.

Methods
The working team summarized the literature on the pharmacology of central neuromodulators and their effects on gastrointestinal sensorimotor function and conducted an evidence-based review on their use for treating FGID syndromes. Because of the paucity of data for FGIDs, we included data for non-gastrointestinal painful disorders and specific symptoms of pain, nausea, and vomiting. This information was combined into a final document comprising a synthesis of available evidence and recommendations for clinical use guided by the research and clinical experience of the experts on the committee.

Results
The evidence-based review on neuromodulators in FGID, restricted by the limited available controlled trials, was integrated with open-label studies and case series, along with the experience of experts to create recommendations using a consensus (Delphi) approach. Due to the diversity of conditions and complexity of treatment options, specific recommendations were generated for different FGIDs. However, some general recommendations include: (1) low to modest dosages of tricyclic antidepressants provide the most convincing evidence of benefit for treating chronic gastrointestinal pain and painful FGIDs and serotonin noradrenergic reuptake inhibitors can also be recommended, though further studies are needed; (2) augmentation, that is, adding a second treatment (adding quetiapine, aripiprazole, buspirone α2δ ligand agents) is recommended when a single medication is unsuccessful or produces side effects at higher dosages; (3) treatment should be continued for 6−12 months to potentially prevent relapse; and (4) implementation of successful treatment requires effective communication skills to improve patient acceptance and adherence, and to optimize the patient−provider relationship.

Conclusions
Based on systematic and selectively focused review and the consensus of a multidisciplinary panel, we have provided summary information and guidelines for the use of central neuromodulators in the treatment of chronic gastrointestinal symptoms and FGIDs. Further studies are needed to confirm and refine these recommendations.

 

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