Management of Refractory Functional Gastrointestinal Disorders: What
                    Role Should Psychiatrists Have?

Mohsen Khosravi; Abdullah A. Alzahrani; Thikra M. Muhammed; Ahmed Hjazi; Huda H. Abbas; Mervat A. AbdRabou; Karrar H. Mohmmed; Pallavi Ghildiyal; Alexey Yumashev; Ahmed Elawady; Sahel Sarabandi

doi:10.1055/a-2331-7684

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2025; 58(01): 14-24
DOI: 10.1055/a-2331-7684

Review

Management of Refractory Functional Gastrointestinal Disorders: What Role Should Psychiatrists Have?

Mohsen Khosravi

¹Department of Psychiatry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

²Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

,

Abdullah A. Alzahrani

³Department of Orthopedic and Spine Surgeon, Taif University, Taif, Saudi Arabia

,

Thikra M. Muhammed

⁴Department of Biotechnology, College of Applied Sciences, University of Fallujah, Al-anbar, Iraq

,

Ahmed Hjazi

⁵Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia

,

Huda H. Abbas

⁶National University of Science and Technology, Dhi Qar, Iraq

,

Mervat A. AbdRabou

⁷Department of Biology, College of Science, Jouf University, Sakaka, Saudi Arabia

,

Karrar H. Mohmmed

⁸Scientific Research Center, Al-Ayen University, Thi-Qar, Iraq

,

Pallavi Ghildiyal

⁹Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India

,

Alexey Yumashev

¹⁰Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Moscow, Russia

,

Ahmed Elawady

¹¹College of technical engineering, the Islamic University, Najaf, Iraq

¹²College of technical engineering, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq

¹³College of technical engineering, the Islamic University of Babylon, Babylon, Iraq

,

Sahel Sarabandi

¹⁴Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

› Author Affiliations

Abstract

Currently, it has been stated that psychiatric and psychological problems are equally paramount aspects of the clinical modulation and manifestation of both the central nervous and digestive systems, which could be used to restore balance. The present narrative review aims to provide an elaborate description of the bio-psycho-social facets of refractory functional gastrointestinal disorders, psychiatrists’ role, specific psychiatric approach, and the latest psychiatric and psychological perspectives on practical therapeutic management. In this respect, “psyche,” “psychiatry,” “psychology,” “psychiatrist,” “psychotropic,” and “refractory functional gastrointestinal disorders” (as the keywords) were searched in relevant English publications from January 1, 1950, to March 1, 2024, in the PubMed, Web of Science, Scopus, EMBASE, Cochrane Library, and Google Scholar databases. Eventually, the narrative technique was adopted to reach a compelling story with a high level of cohesion through material synthesis. The current literature recognizes the brain-gut axis modulation as a therapeutic target for refractory functional gastrointestinal disorders and the bio-psycho-social model as an integrated framework to explain disease pathogenesis. The results also reveal some evidence to affirm the benefits of psychotropic medications and psychological therapies in refractory functional gastrointestinal disorders, even when psychiatric symptoms were absent. It seems that psychiatrists are required to pay higher levels of attention to both the assessment and treatment of patients with refractory functional gastrointestinal disorders, accompanied by educating and training practitioners who take care of these patients.

Keywords

management - psychiatrist - refractory functional gastrointestinal disorders

Full Text

References

References
1 Sperber AD, Bangdiwala SI, Drossman DA. et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation Global Study. Gastroenterology 2021; 160: 99-114.e3
2 Black CJ, Drossman DA, Talley NJ. et al. Functional gastrointestinal disorders: Advances in understanding and management. Lancet 2020; 396: 1664-1674
3 Drossman DA. Functional gastrointestinal disorders: History, pathophysiology, clinical features, and Rome IV. Gastroenterology 2016; 150: 1262-1279.e2
4 Young JM, Solomon MJ. How to critically appraise an article. Nat Clin Pract Gastroenterol Hepatol 2009; 6: 82-91
5 MacLure M. ‘Clarity bordering on stupidity’: Where’s the quality in systematic review? 1st ed. London: Routledge; 2007
6 Yan L, Zhang X, Li Y. et al. The role of psychological factors in functional gastrointestinal disorders: A systematic review and meta-analysis. Int J Colorectal Dis 2023; 38: 65
7 Gong W, Guo P, Li Y. et al. Role of the gut-brain axis in the shared genetic etiology between gastrointestinal tract diseases and psychiatric disorders: A genome-wide pleiotropic analysis. JAMA Psychiatry 2023; 80: 360-370
8 Engel GL. The need for a new medical model: A challenge for biomedicine. Science 1977; 196: 129-136
9 Drossman DA. Gastrointestinal illness and the biopsychosocial model. Psychosom Med 1998; 60: 258-267
10 Van Oudenhove L, Levy RL, Crowell MD. et al. Biopsychosocial aspects of functional gastrointestinal disorders: How central and environmental processes contribute to the development and expression of functional gastrointestinal disorders. Gastroenterology 2016; 150: 1355-1367.e2
11 Adam B, Liebregts T, Holtmann G. Mechanisms of disease: genetics of functional gastrointestinal disorders—searching the genes that matter. Nat Clin Pract Gastroenterol Hepatol 2007; 4: 102-110
12 Saito YA, Mitra N, Mayer EA. Genetic approaches to functional gastrointestinal disorders. Gastroenterology 2010; 138: 1276-1285
13 Mukhtar K, Nawaz H, Abid S. Functional gastrointestinal disorders and gut-brain axis: What does the future hold?. World J Gastroenterol 2019; 25: 552-566
14 Jones MP, Crowell MD, Olden KW. et al. Functional gastrointestinal disorders: An update for the psychiatrist. Psychosomatics 2007; 48: 93-102
15 Koloski NA, Jones M, Kalantar J. et al. The brain–gut pathway in functional gastrointestinal disorders is bidirectional: A 12-year prospective population-based study. Gut 2012; 61: 1284-1290
16 Koloski NA, Jones M, Talley NJ. Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: A 1-year population-based prospective study. Aliment Pharmacol Ther 2016; 44: 592-600
17 Aziz I, Palsson OS, Törnblom H. et al. The prevalence and impact of overlapping Rome IV-diagnosed functional gastrointestinal disorders on somatization, quality of life, and healthcare utilization: A cross-sectional general population study in three countries. Am J Gastroenterol 2018; 113: 86-96
18 Del Colle A, Israelyan N, Gross Margolis K. Novel aspects of enteric serotonergic signaling in health and brain-gut disease. Am J Physiol Gastrointest Liver Physiol 2020; 318: G130-G143
19 Fikree A, Byrne P. Management of functional gastrointestinal disorders. Clin Med 2021; 21: 44-52
20 Basnayake C, Kamm MA, Stanley A. et al. Long-term outcome of multidisciplinary versus standard gastroenterologist care for functional gastrointestinal disorders: A randomized trial. Clin Gastroenterol Hepatol 2022; 20: 2102-2111.e9
21 Basnayake C, Kamm MA, Stanley A. et al. Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): An open-label, single-centre, randomised controlled trial. Lancet Gastroenterol Hepatol 2020; 5: 890-809
22 Șchiopu CG, Ștefănescu C, Boloș A. et al. Functional gastrointestinal disorders with psychiatric symptoms: Involvement of the microbiome–gut–brain axis in the pathophysiology and case management. Microorganisms 2022; 10: 2199
23 Botha C, Drossman D. Functional GI disorders and psychiatry. Psychiatric Times. 2011 https://www.psychiatrictimes.com/view/functional-gi-disorders-and-psychiatry. Accessed 11 Nov 2011.
24 Olden KW, Drossman DA. Psychologic and psychiatric aspects of gastrointestinal disease. Med Clin North Am 2000; 84: 1313-1327
25 Drossman DA. Diagnosing and treating patients with refractory functional gastrointestinal disorders. Ann Intern Med 1995; 123: 688-697
26 Leserman J, Drossman DA. Relationship of abuse history to functional gastrointestinal disorders and symptoms: Some possible mediating mechanisms. Trauma Violence Abuse 2007; 8: 331-343
27 Zamani M, Alizadeh-Tabari S, Zamani V. Systematic review with meta-analysis: The prevalence of anxiety and depression in patients with irritable bowel syndrome. Aliment Pharmacol Ther 2019; 50: 132-143
28 Zhang QE, Wang F, Qin G. et al. Depressive symptoms in patients with irritable bowel syndrome: A meta-analysis of comparative studies. Int J Biol Sci 2018; 14: 1504-1512
29 Labus JS, Mayer EA, Jarcho J. et al. Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women. Gut 2011; 60: 1196-1203
30 Ford AC, Luthra P, Tack J. et al. Efficacy of psychotropic drugs in functional dyspepsia: Systematic review and meta-analysis. Gut 2017; 66: 411-420
31 Törnblom H, Drossman DA. Psychotropics, antidepressants, and visceral analgesics in functional gastrointestinal disorders. Curr Gastroenterol Rep 2018; 20: 58
32 Xiong N, Duan Y, Wei J. et al. Antidepressants vs. placebo for the treatment of functional gastrointestinal disorders in adults: A systematic review and meta-analysis. Front Psychiatry 2018; 9: 659
33 Black CJ, Yuan Y, Selinger CP. et al. Efficacy of soluble fibre, antispasmodic drugs, and gut–brain neuromodulators in irritable bowel syndrome: A systematic review and network meta-analysis. Lancet Gastroenterol Hepatol 2020; 5: 117-131
34 Savarino E, Zingone F, Barberio B. et al. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J 2022; 10: 556-584
35 Gershon MD, Tack J. The serotonin signaling system: From basic understanding to drug development for functional GI disorders. Gastroenterology 2007; 132: 397-414
36 Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron 2007; 55: 377-391
37 Drossman DA. Beyond tricyclics: New ideas for treating patients with painful and refractory functional gastrointestinal symptoms. Am J Gastroenterol 2009; 104: 2897-2902
38 Morgan V, Pickens D, Gautam S. et al. Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome. Gut 2005; 54: 601-607
39 Brunoni AR, Lopes M, Fregni F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: Implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol 2008; 11: 1169-1180
40 Colucci-D’Amato L, Speranza L, Volpicelli F. Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. Int J Mol Sci 2020; 21: 7777
41 Dharmshaktu P, Tayal V, Kalra BS. Efficacy of antidepressants as analgesics: A review. J Clin Pharmacol 2012; 52: 6-17
42 Finnerup NB, Attal N, Haroutounian S. et al. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol 2015; 14: 162-173
43 Drossman DA, Tack J, Ford AC. et al. Neuromodulators for functional gastrointestinal disorders (disorders of gut−brain interaction): A Rome foundation working team report. Gastroenterology 2018; 154: 1140-1171.e1
44 Ford AC, Lacy BE, Harris LA. et al. Effect of antidepressants and psychological therapies in irritable bowel syndrome: An updated systematic review and meta-analysis. Am J Gastroenterol 2019; 114: 21-39
45 Chaves J, Pita I, Libânio D. et al. Pharmacological treatment of functional dyspepsia: An old story revisited or a new story to be told? A clinical review. GE Port J Gastroenterol 2022; 30: 86-97
46 Ford AC, Wright-Hughes A, Alderson SL. et al. Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023; 402: 1773-1785
47 Ferreira GE, Abdel-Shaheed C, Underwood M. et al. Efficacy, safety, and tolerability of antidepressants for pain in adults: Overview of systematic reviews. BMJ 2023; 380: e072415
48 Tang Y, Song J, Zhu Y. et al. Analysis of clinical characteristics of centrally mediated abdominal pain syndrome, exploration of diagnostic markers and its relationship with the efficacy of duloxetine treatment. Medicine (Baltimore) 2022; 101: e32134
49 Acharekar MV, Saldivia SE, Unnikrishnan S. et al. A systematic review on the efficacy and safety of selective serotonin reuptake inhibitors in gastrointestinal motility disorders: More control, less risk. Cureus 2022; 14: e27691
50 Manolakis AC, Broers C, Geysen H. et al. Effect of citalopram on esophageal motility in healthy subjects—implications for reflux episodes, dysphagia, and globus. Neurogastroenterol Motil 2019; 31: e13632
51 Akama F, Mikami K, Watanabe N. et al. Efficacy of mirtazapine on irritable bowel syndrome with anxiety and depression: A case study. Neurogastroenterol Motil 2019; 31: e13632
52 Tack J, Ly HG, Carbone F. et al. Efficacy of mirtazapine in patients with functional dyspepsia and weight loss. Clin Gastroenterol Hepatol 2016; 14: 385-392.e4
53 Jimenez XF, Sundararajan T, Covington EC. A systematic review of atypical antipsychotics in chronic pain management. Clin J Pain 2018; 34: 585-591
54 Grover M, Dorn SD, Weinland SR. et al. Atypical antipsychotic quetiapine in the management of severe refractory functional gastrointestinal disorders. Dig Dis Sci 2009; 54: 1284-1291
55 Ichikawa J, Li Z, Dai J. et al. Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex: Role of 5-HT1A receptor agonism. Brain Res 2002; 956: 349-357
56 Navari RM. Olanzapine for the prevention and treatment of chronic nausea and chemotherapy-induced nausea and vomiting. Eur J Pharmacol 2014; 722: 180-186
57 Sobin HW, Heinrich TW, Drossman DA. Central neuromodulators for treating functional GI disorders: A primer. Am J Gastroenterol 2017; 112: 693-702
58 Rossano F, Caiazza C, Zotti N. et al. The efficacy, safety, and adverse events of azapirones in anxiety disorders: A systematic review and meta-analysis of randomized controlled trials. Eur Neuropsychopharmacol 2023; 76: 23-51
59 Tack J, Janssen P, Masaoka T. et al. Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia. Clin Gastroenterol Hepatol 2012; 10: 1239-1245
60 Taghvaei T, Elyasi F, Rahbar Z. et al. Effectiveness of buspirone in patients with functional dyspepsia: A randomized, double-blind, placebo-controlled study. Middle East J Dig Dis 2021; 13: 302-313
61 Papakostas GI, Nutt DJ, Hallett LA. et al. Resolution of sleepiness and fatigue in major depressive disorder: A comparison of bupropion and the selective serotonin reuptake inhibitors. Biol Psychiatry 2006; 60: 1350-1355
62 Staller K, Thurler AH, Reynolds JS. et al. Gabapentin improves symptoms of functional dyspepsia in a retrospective, open-label cohort study. J Clin Gastroenterol 2019; 53: 379-384
63 Shafigh-Ardestani MH, Karami-Horestani M, Emami B. et al. Evaluating the effect of oral gabapentin on the improvement of gastrointestinal symptoms in patients with functional dyspepsia resistant to conventional treatments. Adv Biomed Res 2019; 8: 53
64 Xu R, Wang Y, Han W. Randomized clinical trial: The effects of pregabalin for centrally mediated abdominal pain syndrome. Therap Adv Gastroenterol 2023; 16 17562848231152334
65 Kotikula I, Thinrungroj N, Pinyopornpanish K. et al. Randomised clinical trial: The effects of pregabalin vs placebo on functional dyspepsia. Aliment Pharmacol Ther 2021; 54: 1026-1032
66 Hojo M, Nagahara A, Asaoka D. et al. A systematic review of the effectiveness of antianxiety and antidepressive agents for functional dyspepsia. Intern Med 2017; 56: 3127-3133
67 Black CJ, Thakur ER, Houghton LA. et al. Efficacy of psychological therapies for irritable bowel syndrome: Systematic review and network meta-analysis. Gut 2020; 69: 1441-1451
68 Mikocka-Walus A, Evans S, Linardon J. et al. Psychotherapy appears to improve symptoms of functional dyspepsia and anxiety: Systematic review with meta-analysis. Psychol Health Med 2023; 28: 1309-1335
69 Wei Z, Xing X, Tantai X. et al. The effects of psychological interventions on symptoms and psychology of functional dyspepsia: A systematic review and meta-analysis. Front Psychol 2022; 13: 827220
70 Rodrigues DM, Motomura DI, Tripp DA. et al. Are psychological interventions effective in treating functional dyspepsia? A systematic review and meta-analysis. J Gastroenterol Hepatol 2021; 36: 2047-2057
71 Keefer L, Ballou SK, Drossman DA. et al. A Rome working team report on brain-gut behavior therapies for disorders of gut-brain interaction. Gastroenterology 2022; 162: 300-315
72 Fiske A, Henningsen P, Buyx A. Your robot therapist will see you now: Ethical implications of embodied artificial intelligence in psychiatry, psychology, and psychotherapy. J Med Internet Res 2019; 21: e13216
73 Rupp SK, Stengel A. Bi-directionality of the microbiota-gut-brain axis in patients with functional dyspepsia: Relevance of psychotherapy and probiotics. Front Neurosci 2022; 16: 844564
74 Jiménez-Ocaña A, Pantoja A, Valderrama MA. et al. A systematic review of technology-aided stress management systems: Automatic measurement, detection and control. IEEE Access 2023; 11: 116109-116126
75 Zhuang JX. Psychosomatic care plus WeChat communication relaxation therapy in patients with functional dyspepsia. World Chin J Digestol 2017; 25: 1191-1195
76 Xiong Y, Xing H, Hu L. et al. Effects of comfort care on symptoms, gastric motility, and mental state of patients with functional dyspepsia. Medicine 2019; 98: e16110
77 Haug TT, Wilhelmsen I, Svebak S. et al. J Psychosom Res 1994; 38: 735-744
78 Dehghanizade Z, Zargar Y, Honarmand MM. et al. The effectiveness of cognitive behavior stress management on functional dyspepsia symptoms. J Adv Med Educ Prof 2015; 3: 45-49
79 Law M, Pickering I, Bartlett E. et al. Cognitive behavioural therapy-based interventions for gastroduodenal disorders of gut-brain interaction: A systematic review. J Psychosom Res 2023; 175: 111516
80 Ardi Z, Eseadi C, Yuniarti E. et al. Efficacy of cognitive behavioral therapy with local wisdom and web-based counseling on generalized anxiety disorders and functional gastrointestinal disorders in adolescent college girls: Protocol for a randomized controlled trial. JMIR Res Protoc 2023; 12: e50316
81 Palsson OS, Whitehead WE. Psychological treatments in functional gastrointestinal disorders: A primer for the gastroenterologist. Clin Gastroenterol Hepatol 2013; 11: 208-216
82 Hamilton J, Guthrie E, Creed F. et al. A randomized controlled trial of psychotherapy in patients with chronic functional dyspepsia. Gastroenterology 2000; 119: 661-669
83 Faramarzi M, Azadfallah P, Book HE. et al. A randomized controlled trial of brief psychoanalytic psychotherapy in patients with functional dyspepsia. Asian J Psychiatr 2013; 6: 228-234
84 Faramarzi M, Azadfallah P, Book HE. et al. The effect of psychotherapy in improving physical and psychiatric symptoms in patients with functional dyspepsia. Iran J Psychiatry 2015; 10: 43-49
85 Orive M, Barrio I, Orive VM. et al. A randomized controlled trial of a 10 week group psychotherapeutic treatment added to standard medical treatment in patients with functional dyspepsia. J Psychosom Res 2015; 78: 563-568
86 Calvert EL, Houghton LA, Cooper P. et al. Long-term improvement in functional dyspepsia using hypnotherapy. Gastroenterology 2002; 123: 1778-1785
87 Miller V, Whorwell PJ. Hypnotherapy for functional gastrointestinal disorders: A review. Int J Clin Exp Hypn 2009; 57: 279-292
88 Vasant DH, Whorwell PJ. Gut-focused hypnotherapy for functional gastrointestinal disorders: Evidence-base, practical aspects, and the Manchester protocol. Neurogastroenterol Motil 2019; 31: e13573
89 Lacy BE, Chase RC, Cangemi DJ. The treatment of functional dyspepsia: Present and future. Expert Rev Gastroenterol Hepatol 2023; 17: 9-20
90 Popa SL, Chiarioni G, David L. et al. The efficacy of hypnotherapy in the treatment of functional dyspepsia. Am J Ther 2019; 26: e704-e713
91 Browne PD, de Bruijn CM, Speksnijder EM. et al. Skills or pills: Randomized trial comparing hypnotherapy to medical treatment in children with functional nausea. Clin Gastroenterol Hepatol 2022; 20: 1847-1856.e6
92 Basnayake C, Kamm MA, Stanley A. et al. Long-term outcome of multidisciplinary versus standard gastroenterologist care for functional gastrointestinal disorders: A randomized trial. Clin Gastroenterol Hepatol 2022; 20: 2102-2111.e9
93 Zhang YB, Huang ZY, Jin JW. et al. Rectal sensitivity and associated factors in patients with different subtypes of functional defecation disorder. Eur J Gastroenterol Hepatol 2023; 35: 1370-1374
94 Sahid S, Kamarulzaman MY, Mustafa JB. et al. Biofeedback therapy for anorectal functional disorder: Malaysian colorectal tertiary centre experience. Ann Med Surg 2022; 79: 103848
95 Moore D, Young CJ. A systematic review and meta-analysis of biofeedback therapy for dyssynergic defaecation in adults. Tech Coloproctol 2020; 24: 909-918
96 Basnayake C, Kamm MA, Stanley A. et al. Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): An open-label, single-centre, randomised controlled trial. Lancet Gastroenterol Hepatol 2020; 5: 890-899
97 Alam MJ, Chen JD. Electrophysiology as a tool to decipher the network mechanism of visceral pain in functional gastrointestinal disorders. Diagnostics 2023; 13: 627
98 Weltens N, Iven J, Van Oudenhove L. et al. The gut–brain axis in health neuroscience: Implications for functional gastrointestinal disorders and appetite regulation. Ann N Y Acad Sci 2018; 1428: 129-150
99 Mukhtar K, Nawaz H, Abid S. Functional gastrointestinal disorders and gut-brain axis: What does the future hold?. World J Gastroenterol 2019; 25: 552-566
100 Kano M, Dupont P, Aziz Q. et al. Understanding neurogastroenterology from neuroimaging perspective: A comprehensive review of functional and structural brain imaging in functional gastrointestinal disorders. J Neurogastroenterol Motil 2018; 24: 512-527