Centrally Targeted Pharmacotherapy for Chronic Abdominal Pain: Understanding and Management

Törnblom, Hans; Drossman, Douglas A.

doi:10.1007/164_2016_106

Cited by 7 publications

(13 citation statements)

References 92 publications

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“…Consistently, recent systematic reviews and meta-analysis indicated that antidepressants were effective for IBS (17, 18). Clinical reviews also supported the efficacy of antidepressants for patients with FD (10), functional esophageal disorders (19), and functional abdominal pain (20). Nevertheless, compared carefully, the studies included and the effect sizes in each review still differed.…”

Section: Discussionmentioning

confidence: 99%

“…According to the recommendations of the Cochrane Collaboration (20), the risk of bias was assessed from eight aspects: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and of personnel/care providers (performance bias), blinding of outcome assessor (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), group similarity at baseline (selection bias), and other bias (funding bias). We explicitly judged each of these eight criteria as exemplifying a low, high, or unclear risk of bias.…”

Section: Methodsmentioning

confidence: 99%

“…Nevertheless, evidence yielded from those studies was contradictory. Systematic reviews and clinical guidelines before 2008 basically found no clear evidence of benefit for antidepressants (14–16), while updated reviews generally indicated that they were effective for the treatment of IBS (17, 18), FD (10), FCP (19), and functional abdominal pain (20). However, unlike the real world, most researches only focused on one specific subtype of FGIDs, while the comorbidity with other subtypes of FGIDs and mental disorders often was not accounted for.…”

Section: Introductionmentioning

confidence: 99%

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Antidepressants vs. Placebo for the Treatment of Functional Gastrointestinal Disorders in Adults: A Systematic Review and Meta-Analysis

et al. 2018

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Objective: To integrate high-quality evidence of the efficacy of antidepressants across different subtypes of functional gastrointestinal disorders (FGIDs).Methods: The Medline, PsycINFO, EMBASE, the Cochrane Library, and Chinese local database were searched up to October 1, 2017. Keywords included all subtypes of FGIDs, antidepressants, and randomized controlled trials (RCTs). We included RCTs with low to moderate risks of bias in comparing antidepressants with placebos as the only intervention in treating adult patients with FGIDs (PROSPERO ID: CRD42015030123). Language was restricted to English or Chinese. Data extraction was independently carried out by two authors, following the Cochrane Handbook for systematic reviews.Results: Of 2,460 records identified, 31 studies reporting on 2,340 participants were included in the meta-analysis. Antidepressants were more effective than placebos in terms of the rate of responder [RR = 1.35 (95% CI 1.12 to 1.63)], and the reduction of target gastrointestinal symptoms [SMD = −0.94 (95% CI −1.33 to −0.54)], and disability severity (moderate effect sizes). Those effects partly remained both at the presence and absence of comorbid depression, and among different subtypes of FGIDs. Subgroup analyses confirmed the benefit of tricyclic and tetracyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and trazodone. Efficacy of serotonin and norepinephrine reuptake inhibitors (SNRIs), low doses of antidepressants, and antidepressants in intermediate to long term treatment was inconclusive due to the scarcity of eligible evidence. Compared to placebo, patients on antidepressants reported more adverse events [RR = 1.91 (95% CI 1.23 to 2.96)] and more frequent withdrawal. On average one in 7.4 (95% CI 5.4 to 11.9) patients treated with antidepressants responded, while one in 4.8 (95% CI 3.7 to 6.8) experienced certain adverse effects.Conclusions: Antidepressants were inferior to placebo in terms of tolerability and partly superior regarding efficacy. Before prescribing antidepressants, the benefits and side effects should be carefully evaluated.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antidepressants vs. Placebo for the Treatment of Functional Gastrointestinal Disorders in Adults: A Systematic Review and Meta-Analysis

et al. 2018

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“…The afferent nerve signals involved in the transmission of pain reach the brain through a chain of 3 orders of neurons from the primary spinal afferent arising from the gut to second-order neurons from the dorsal horn of the spinal cord to the thalamus and then to the midbrain ( 6 , 10 ).…”

Section: Why Use Neuromodulators In Ibs?mentioning

confidence: 99%

Central Neuromodulators in Irritable Bowel Syndrome: Why, How, and When

Hanna-Jairala,

Drossman

2024

Am J Gastroenterol

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Irritable bowel syndrome are responsive to treatments using central neuromodulators. Central neuromodulators work by enhancing the synaptic transmission of 5-hydroxytryptamine, noradrenalin and dopamine, achieving a slower regulation or desensitization of their postsynaptic receptors. Central neuromodulators act on receptors along the brain-gut axis, so they are useful in treating psychiatric comorbidities, modifying gut motility, improving central downregulation of visceral signals and enhancing neurogenesis in patients with IBS. Choosing a central neuromodulator for treating IBS should be according to the pharmacological properties and the predominant symptoms. The first-line treatment for pain management in IBS is using tricyclic antidepressants. An alternative for pain management is the serotonin and noradrenaline reuptake inhibitors. Selective serotonin reuptake inhibitors are useful when symptoms of anxiety and hypervigilance are dominant but are not helpful for treating abdominal pain. The predominant bowel habit is helpful when choosing a neuromodulator to treat IBS; SSRIs help constipation, not pain, but may cause diarrhea; TCAs help diarrhea but may cause constipation. A clinical response may occur in 6-8 weeks, but long-term treatment (usually 6-12 months) is required after the initial response to prevent relapse. Augmentation therapy may be beneficial when the therapeutic effect of the first agent is incomplete or associated with side effects. It is recommended to reduce the dose of the first agent and add a second complementary treatment. This may include an atypical antipsychotic or brain-gut behavioral treatment. When tapering central neuromodulators, the dose should be reduced slowly over 4 weeks but may take longer when discontinuation effects occur.

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“…Following thorough investigation, most patients will not have a structural cause identified and will be classified as having functional biliary-type, the detailed management of which is outside the remit of this review. Low-dose tricyclic antidepressants have shown benefit in reducing overall symptomatology and pain indices 47. Additionally in a recent pilot study, the antidepressant duloxetine, a selective and potent balanced dual 5-hydroxytryptamine (5-HT) and serotonin–norepinephrine reuptake inhibitor, was found to be beneficial in 90% (n=10) of patients with suspected SOD 48…”

Section: Evolution Of Sodmentioning

confidence: 99%