1. Central neuromodulators (antidepressants, antipsychotics and other CNS targeted medications) are increasingly used for treatment of functional GI 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. But a recent Rome Foundation Working Team report published in the March 2018 issue of Gastroenterology summarized available research evidence and clinical experience to provide guidance and treatment recommendations. This is the first and most comprehensive review of the use of central neuromodulators for painful functional gastrointestinal disorders (FGIDs) like irritable bowel syndrome (IBS), centrally mediated abdominal pain and other painful symptoms.


  1. One key point is that we are changing the antiquated use of terminology like “antidepressants” and “antipsychotics”, which were developed originally to treat psychiatric disorders. We are now substituting the term neuromodulators, which better reflects our understanding that these are disorders of gut-brain interaction (Rome IV).  Thus, the antidepressants and other meds working in the brain are central neuromodulators and the medications working in the enteric nervous system of the bowel are peripheral neuromodulators.   In that context, we are in effect treating the new understanding of these disorders relating to dysfunction in the brain-gut often in doses lower than for treating major psychiatric disorders.  Some of the major findings of this report are that tricyclic antidepressants (TCAs) and SNRIs do work for pain.


  1. However, the report also noted that if a single medication does not work or has side effects, doctors may combine two or more treatments to help those patients that don’t initially respond.  This is called augmentation treatment where you can maximize benefit even with lower doses by using two or more treatments that act on different neuroreceptors. Also, patients are kept on them for a year or more because we are learning that the longer you are on it the more “rewiring” of the brain occurs which eventually leads to relapse prevention.  It is a way to provide ample time to reverse the dysfunctional circuitry causing the FGID problem in the first place, and it may reverse the neurodegeneration that occurs over time.


  1. Finally, if there are frequent side effects or a failure to respond to several medications we recommend doing pharmacogenomic testing, a new method to evaluate how patients genetically metabolize these medications.  Also, it’s important to realize that the ways in which we employ these treatments for FGIDs is different from how psychiatrists treat psychiatric disorders.  In fact, psychiatrists are not well versed in these methods because they are focusing on emotional illness not GI symptoms including pain, vomiting and bowel disturbance where these treatments work.


  1. Patients struggling with chronic GI pain should know that they can be helped!  The Rome Foundation is reducing the sense of stigma by avoiding unnecessary attributions relating these the use of central neuromodulators to psychiatric disorders.  We believe there will be a big difference in acceptance and benefit to patients over the next few years as more and more physicians use them with a proper understanding of how they can benefit these chronic gastrointestinal symptoms.  With regard to DrossmanCare – we have been taking care of hundreds of patients over the years in this manner and helping patients with the most refractory symptoms who have been to other medical centers without benefit.  In our practice [see below citation], the combination of good communication skills to help patients understand the physiological value of these medications coupled with our knowledge of selecting the best medications or combinations of medications to treat these FGIDs make a difference to help those that have previously failed treatment.  I left UNC in part out of a commitment to improve patients suffering from these disorders using these methods and now not only are we seeing it happen, but our methods are being communicated to gastroenterologists and other providers around the world.


Related Resources

“Central Neuromodulators for Chronic GI Pain and FGIDs (DGBI) – A Rome Foundation Working Team Report”, Gastroenterology. 2017 Dec 21. pii: S0016-5085(17)36718-5. doi: 10.1053/j.gastro.2017.11.279; Published in print March, 2018

Beyond Tricyclics: New Ideas for Treating Patients With Painful and Refractory Functional Gastrointestinal Symptoms, The American Journal of Gastroenterology(2009) 104, 2897–2902 (2009) doi:10.1038/ajg.2009.341