Clinical efficacy and safety of ketotifen in treating irritable bowel syndrome with diarrhea

Wang, Jing; Wang, Yucheng; Zhou, Haibin; Gu, Weigang; Wang, Xia; Yang, Jianfeng

doi:10.1097/meg.0000000000001737

Cited by 22 publications

(15 citation statements)

References 32 publications

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“…In double‐blind trials, cromoglycate was superior to placebo in reducing symptoms in IBS patients with food intolerance 82‐84 . A placebo‐controlled trial found that ketotifen, a mast cell stabilizer with histamine H 1 antagonist properties, decreased IBS symptoms and improved quality of life but did not reduce mast cells 85,86 …”

Section: Role Of Mast Cells In Ibs Pathogenesismentioning

confidence: 99%

Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome

Hasler

Grabauskas

Singh

et al. 2022

Neurogastroenterology Motil

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Abnormalities of mast cell structure or function may play prominent roles in irritable bowel syndrome (IBS) symptom genesis. Mast cells show close apposition to sensory nerves and release bioactive substances in response to varied stimuli including infection, stress, and other neuroendocrine factors. Most studies focus on patients who develop IBS after enteric infection or who report diarrhea-predominant symptoms. Three topics underlying IBS pathogenesis have been emphasized in recent investigations. Visceral hypersensitivity to luminal stimulation is found in most IBS patients and may contribute to abdominal pain. Mast cell dysfunction also may disrupt epithelial barrier function which alters mucosal permeability potentially leading to altered bowel function and pain. Mast cell products including histamine, proteases, prostaglandins, and cytokines may participate in hypersensitivity and permeability defects, especially with diarrhea-predominant IBS. Recent experimental evidence indicates that the pronociceptive effects of histamine and proteases are mediated by the generation of prostaglandins in the mast cell. Enteric microbiome interactions including increased mucosal bacterial translocation may activate mast cells to elicit inflammatory responses underlying some of these pathogenic effects. Therapies to alter mast cell activity (mast cell stabilizers) or function (histamine antagonists) have shown modest benefits in IBS. Future investigations will seek to define patient subsets with greater potential to respond to therapies that address visceral hypersensitivity, epithelial permeability defects, and microbiome alterations secondary to mast cell dysfunction in IBS.

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Section: Role Of Mast Cells In Ibs Pathogenesismentioning

confidence: 99%

Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome

Hasler

Grabauskas

Singh

et al. 2022

Neurogastroenterology Motil

View full text Add to dashboard Cite

show abstract

“…There is some evidence to support mast cells as therapeutic targets in IBS and FD utilizing medications to inhibit mediator release (e.g., mast cell stabilizers such as cromolyn or ketotifen or anti-siglec 8) or to inhibit mast cell mediators once released (e.g., histamine or cysteinyl leukotriene inhibitors) [18,32,[86][87][88][89][90][91]. One study utilizing cromolyn and one utilizing ketotifen demonstrated evidence of decreased mast cell activation [18,32].…”

Section: Discussionmentioning

confidence: 99%

A Survey of Methodologies for Assessing Mast Cell Density and Activation in Patients with Functional Abdominal Pain Disorders

Friesen

Singh

et al. 2021

Gastrointestinal Disorders

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The aim was to assess methods utilized in assessing mast cell involvement in functional abdominal pain disorders (FAPDs), specifically to describe variability in methods utilized to assess both mast cell density and activation and determine if a consensus exists. After a literature search identified 70 manuscripts assessing mast cell density, data were extracted including FAPD diagnosis, site of biopsy, selection of microscopic fields analyzed, selection of mucosal region analyzed, method of mast cell identification, method to assess mast cell density, and if performed, method to assess mast cell activation. There appears to be some consensus favoring inmmunohistochemical stains over histochemical stains for identifying mast cells. Otherwise, considerable variability exists in methodology for assessing mast cell density and activation. Regardless of method, approximately 80% of studies found increased mast cell density and/or activation in comparison to controls with no method being superior. A wide variety of methods have been employed to assess mast cell density and activation with no well-established consensus and inadequate data to recommend specific approaches. The current methodology providing physiologic information needs to be translated to a standard methodology providing clinical information with the development of criteria establishing abnormal density and/or activation, and more importantly, predicting treatment response.

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“…86 In a more recent study 1 mg twice daily of ketotifen improved visceral hypersensitivity in IBS-D by reducing number and activity of mast cells in the terminal ileum. 87 With this preliminary evidence (Table 1), a safety profile similar to placebo and being relatively inexpensive, ketotifen could be considered among the second-line options for IBS pain especially in patients with diarrhoea predominance (Figure 1).…”

Section: Le Ss Well-e Viden Ced Current Approache S To Ibs Pain Tre Atmentmentioning

confidence: 99%

Review article: current and future treatment approaches for pain in IBS

Paine

2021

Aliment Pharmacol Ther

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SummaryBackgroundAbdominal pain is a core symptom of IBS and a primary driver of care seeking. Visceral hypersensitivity is a key pathophysiological mechanism and therapeutic target for pain in IBS, with components of peripheral and central sensitisation and psychological factors.AimTo review current and future treatment approaches specifically for the pain component of IBS.MethodsPubmed search terms included combinations of irritable bowel, pain, visceral hypersensitivity, novel, new, emerging, future and advances.ResultsEstablished non‐pharmacological treatments for IBS pain include the low FODMAP diet, probiotics and psychological interventions, especially hypnotherapy. Tricyclics remain the best evidenced pharmacological approach with GCC agonists, tenapanor, lubiprostone, eluxadoline and 5HT3 antagonists second line according to patient characteristics and availability. Less well‐evidenced current options include anti‐spasmodics, peppermint oil, SSRIs, SNRIs, alpha 2 delta ligands, melatonin and histamine antagonists. Patients are vulnerable to iatrogenesis and harmful approaches to be avoided include opioids and unwarranted surgical interventions. For severe pain, the concept of augmentation with combined gut‐brain neuromodulators and psychotherapy in a multi‐disciplinary setting is considered. A plethora of molecular targets and ligands are emerging from pre‐clinical studies, together with early clinical evidence for a range of pharmacological, dietary, neurostimulation and novel psychological treatment delivery methods which are reviewed. The history of such emerging approaches, however, merits both caution and optimism in equal measure.ConclusionsDespite good in‐roads and emerging options, the management of abdominal pain remains one of the biggest challenges and research priorities for patients with IBS.

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Clinical efficacy and safety of ketotifen in treating irritable bowel syndrome with diarrhea

Cited by 22 publications

References 32 publications

Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome

Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome

A Survey of Methodologies for Assessing Mast Cell Density and Activation in Patients with Functional Abdominal Pain Disorders

Review article: current and future treatment approaches for pain in IBS

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